Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study.

Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.

Beyond electrostatic interactions: Ligand shell modulated uptake of bis-conjugated iron oxide nanoparticles by cells.

The effect of the ligand shell on the cellular uptake efficiency was evaluated by a systematic study using fully dispersed 6 nm diameter superparamagnetic iron oxide nanoparticles (SPIONs), mono and bis-conjugated with glycerol phosphate (glyc), dopamine (dopa), 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron) and phosphorylethanolamine (pea). Negatively charged SPION-glyc was more efficiently incorporated than positively charged SPION-pea and SPION-dopa clearly evidencing that there are strong enough short-range interactions in addition to the long-range electrostatic interactions, as measured by the zeta potential, to reverse our expectation on cellular uptake. Those effects were pursued by correlating the nanoparticles incorporation efficiency as a function of the respective zeta potentials and the molar fractions of glyc and pea ligands co-conjugated on the SPION surface. The possibility of associating different ligands to modulate the physicochemical properties and biological events was demonstrated, showing promising perspectives for the development of multifunctional nanosystems for biomedical applications.

Therapeutic potential of low-cost nanocarriers produced by green synthesis: macrophage uptake of superparamagnetic iron oxide nanoparticles.

Aim: The primary goal of this work was to synthesize low-cost superparamagnetic iron oxide nanoparticles (SPIONs) with the aid of coconut water and evaluate the ability of macrophages to internalize them. Our motivation was to determine potential therapeutic applications in drug-delivery systems associated with magnetic hyperthermia. Materials & methods: We used the following characterization techniques: x-ray and electron diffractions, electron microscopy, spectrometry and magnetometry. Results: The synthesized SPIONs, roughly 4 nm in diameter, were internalized by macrophages, likely via endocytic/phagocytic pathways. They were randomly distributed throughout the cytoplasm and mainly located in membrane-bound compartments. Conclusion: Nanoparticles presented an elevated intrinsic loss power value and were not cytotoxic to mammalian cells. Thus, we suggest that low-cost SPIONs have great therapeutic potential.

A reliable protocol for colorimetric determination of iron oxide nanoparticle uptake by cells.

Size, shape, and surface properties of superparamagnetic iron oxide nanoparticles (SPIONs) can influence their interaction with biological systems, particularly the incorporation by tumor cells and consequently the biological activity and efficiency in biomedical applications. Several strategies have been used to evaluate cellular uptake of SPIONs. While qualitative methods are generally based on microscopy techniques, quantitative assays are carried out by techniques such as inductively coupled plasma-mass spectrometry and flow cytometry. However, inexpensive colorimetric methods based on equipments commonly found in chemistry and biochemistry laboratories are preferred for routine measurements. Nevertheless, colorimetric assays must be used judiciously, particularly when nanoparticles are involved, since their interaction with biological constituents tends to lead to quite underestimated results. Thus, herein described is a colorimetric protocol using 2,2'-bipyridine as chromogenic ligand, where each step was optimized and validated by total reflection X-ray fluorescence spectroscopy, realizing a highly reproducible and reliable method for determination of iron content in cells incubated with SPIONs. The limit of blank and limit of detection were determined to be as low as 0.076 and 0.143 µg Fe/mL, using sample volumes as small as 190 µL and a number of cells as low as 2.0 × 105. Furthermore, three different types of surface-functionalized nanoparticles were incorporated in cells and evaluated through this protocol, enabling to monitor the additive effect of o-phosphorylethanolamine (PEA) and folic acid (FA) conjugation on iron oxide nanoparticles (SPION-PEA and SPION-PEA/FA), that enhanced the uptake by HeLa cells, respectively, by four and ten times when compared to SPIONs conjugated with nonbioactive molecules. Graphical abstract Colorimetric determination of superparamagnetic iron oxide nanoparticles (SPIONs) incorporated by cells.

In Haitian women and preschool children, iron absorption from wheat flour-based meals fortified with sodium iron EDTA is higher than that from meals fortified with ferrous fumarate, and is not affected by Helicobacter pylori infection in children.

Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

Exploring cellular uptake of iron oxide nanoparticles associated with rhodium citrate in breast cancer cells.

Nanocarriers have the potential to improve the therapeutic index of currently available drugs by improving their efficacy and achieving therapeutic steady-state levels over an extended period. The association of maghemite-rhodium citrate (MRC) nanoparticles (NPs) has the potential to increase specificity of the cytotoxic action. However, the interaction of these NPs with cells, their uptake mechanism, and subcellular localization need to be elucidated. This work evaluates the uptake mechanism of MRC NPs in metastatic and nonmetastatic breast cancer-cell models, comparing them to a nontumor cell line. MRC NPs uptake in breast cancer cells was more effective than in normal cells, with regard to both the amount of internalized material and the achievement of more strategic intracellular distribution. Moreover, this process occurred through a clathrin-dependent endocytosis pathway with different basal expression levels of this protein in the cell lines tested.

Real-time in vivo monitoring of magnetic nanoparticles in the bloodstream by AC biosusceptometry.

BACKGROUND: We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals. RESULTS: We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols. CONCLUSIONS: These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications.

Autocuidado do cuidador familiar de adultos ou idosos dependentes após a alta hospitalar / Self-care in family caregiver of dependent adults or elderly persons after hospital discharge / El autocuidado del cuidador familiar de adultos o ancianos dependientes tras el alta hospitalaria

Este artigo apresenta uma compreensão sobre o autocuidado do cuidador familiar segundo a teoria de Dorothea Orem. Resulta de uma pesquisa qualitativa com aporte da Teoria Fundamentada nos Dados, utilizando-se das técnicas de visita domiciliar, registro de notas de campo e entrevista semiestruturada com 11 cuidadores, após a internação de familiar em um Hospital Universitário de Minas Gerais. Foram obtidas quatro categorias, destacando uma categoria central, em torno da qual se analisaram as facilidades, dificuldades e estratégias para o autocuidado do cuidador. Entre as dificuldades, foram evidenciadas: tempo insuficiente para os cuidados com a saúde e, entre as facilidades, o apoio de outros familiares. As principais estratégias foram: apoio na fé; revezamento nos cuidados e recursos na comunidade. Concluiu-se que orientações no momento da alta e o acompanhamento de enfermagem após a alta contribuem para o autocuidado do cuidador, atuando sobre suas dificuldades e estimulando suas potencialidades.

This article presents an understanding concerning self-care in family caregivers according to Dorothea Orem's theory. Resulting from a qualitative research based on Grounded Theory, this work uses the techniques of home visiting, field notes and semistructured interviews with 11 caregivers after the hospitalization of a family member in a teaching Hospital located in Minas Gerais. Four categories were found and among them a central category is highlighted from which some facilities, difficulties and strategies for selfcare in caregiver were analyzed. Considering the difficulties, insufficient time for healthcare was noticed whereas the support from other family members appeared as a facility. The main strategies were: faith as a support; shift work in healthcare and community resources. This study demonstrated that hospital discharge guidelines and nursing follow-up after discharge were responsible for positive contributions to self-care in caregivers helping them to overcome their difficulties and enhancing their potentialities.

El artículo presenta una comprensión sobre el autocuidado del cuidador familiar, según la teoría de Dorothea Orem. Resulta de investigación cualitativa con aporte de la Teoría Fundamentada en los Datos, utilizándo se de las técnicas de visitas a domicilio; registro de apuntes de campo y entrevista semiestructurada, tras la internación de un familiar en un hospital universitario de Minas Gerais. Se llegó a cuatro categorías, señalando una categoría central, alrededor de la cual se analizaron las facilidades, dificultades y estrategias para el autocuidado del cuidador. Se evidenció, entre las dificultades, tiempo insuficiente para los cuidados con la salud y, entre las facilidades, el apoyo de otros familiares. Las principales estrategias fueron: apoyo en la fe, revezo en los cuidados y recursos en la comunidad. Se concluyó que orientaciones el momento del alta y el acompañamiento de enfermería tras el alta contribuyen para el autocuidado del cuidador, actuando sobre sus dificultades y estimulando sus potencialidades.

Factors associated with satisfaction at work in Psychosocial Care Centers / Fatores associados à satisfação no trabalho em Centros de Atenção Psicossocial / Factores asociados a la satisfacción en el trabajo en Centros de Atención Psicosocial

OBJECTIVES: to analyze the prevalence of satisfaction at work and identify associated factors in Psychosocial Care Centers. METHOD: cross-sectional study involving 546 workers from 40 Psychosocial Care Centers in the South of Brazil. The satisfaction was identified based on the Assessment Scale of Satisfaction in the Mental Health Team and a logistic regression model was used for the adjusted data analysis. RESULTS: the prevalence of satisfaction at work corresponded to 66.4%. Factors directly associated with satisfaction: higher-level function (except physicians and psychologists), work time of six months or less, making a larger number of home visits, good supervision by the team, possibility to make collective choices and take courses. CONCLUSIONS: the satisfaction is associated with the work organization and conditions and demonstrates the need to invest in team supervisions, in process that democratize the services and in the workers' training. .

OBJETIVOS: analisar a prevalência de satisfação no trabalho e identificar fatores associados em Centros de Atenção Psicossocial. MÉTODO: estudo transversal com 546 trabalhadores de 40 Centros de Atenção Psicossocial, da Região Sul do Brasil. A satisfação foi identificada a partir da Escala de Avaliação da Satisfação da Equipe de Saúde Mental e a análise ajustada dos dados, realizada por modelo de regressão logística. RESULTADOS: prevalência de satisfação no trabalho de 66,4%. Fatores diretamente associados à satisfação: função de nível superior (excetuando médicos e psicólogos), tempo de trabalho menor ou igual a seis meses, realização de maior número de visitas domiciliares, boa supervisão pela equipe, possibilidade de fazer escolhas coletivas e cursos. CONCLUSÕES: a satisfação está associada à organização e às condições do trabalho e demonstra necessidade de se investir em supervisão pelas equipes, em processos que democratizem os serviços e, também, na formação de seus trabalhadores. .

OBJETIVOS: analizar la prevalencia de satisfacción en el trabajo e identificar factores asociados en Centros de Atención Psicosocial. MÉTODO: estudio trasversal con 546 trabajadores de 40 Centros de Atención Psicosocial de la región Sur de Brasil. La satisfacción fue identificada a partir de la Escala de Evaluación de la Satisfacción del Equipo de Salud Mental y el análisis ajustado de los datos efectuado mediante un modelo de regresión logística. RESULTADOS: prevalencia de satisfacción en el trabajo de 66,4%. Factores directamente asociados a la satisfacción: función de nivel superior (excepto médicos y psicólogos), tiempo de trabajo menor o igual a seis meses, efectuar mayor número de visitas a domicilio, boa supervisión por el equipo, posibilidad de hacer opciones colectivas y cursos. CONCLUSIONES: la satisfacción está asociada a la organización y a las condiciones del trabajo y demuestra la necesidad de invertir en supervisión por los equipos, en procesos que democraticen los servicios y también en la formación de sus trabajadores. .

In vitro and in vivo experiments with iron oxide nanoparticles functionalized with DEXTRAN or polyethylene glycol for medical applications: magnetic targeting.

In this research work, DEXTRAN- and polyethylene glycol (PEG)-coated iron-oxide superparamagnetic nanoparticles were synthetized and their cytotoxicity and biodistribution assessed. Well-crystalline hydrophobic Fe3 O4 SPIONs were formed by a thermal decomposition process with d = 18 nm and σ = 2 nm; finally, the character of SPIONs was changed to hydrophilic by a post-synthesis procedure with the functionalization of the SPIONs with PEG or DEXTRAN. The nanoparticles present high saturation magnetization and superparamagnetic behavior at room temperature, and the hydrodynamic diameters of DEXTRAN- and PEG-coated SPIONs were measured as 170 and 120 nm, respectively. PEG- and DEXTRAN-coated SPIONs have a Specific Power Absorption SPA of 320 and 400 W/g, respectively, in an ac magnetic field with amplitude of 13 kA/m and frequency of 256 kHz. In vitro studies using VERO and MDCK cell lineages were performed to study the cytotoxicity and cell uptake of the SPIONs. For both cell lineages, PEG- and DEXTRAN-coated nanoparticles presented high cell viability for concentrations as high as 200 µg/mL. In vivo studies were conducted using BALB/c mice inoculating the SPIONs intravenously and exposing them to the presence of an external magnet located over the tumour. It was observed that the amount of PEG-coated SPIONs in the tumor increased by up to 160% when using the external permanent magnetic as opposed to those animals that were not exposed to the external magnetic field.

Iron (FeSo4) bioavailability in obese subjects submitted to bariatric surgery.

BACKGROUND: Iron bioavailability in obese subjects after the ingestion of a nutritional supplement was the aim of this work. METHODS: Fourteen persons were studied before and after bariatric surgery after the ingestion of a nutritional formulation containing 25 mg iron, 25 g fiber and 800 mg calcium. RESULTS: The following ferremia values (median and minimum--maximum) were obtained before and after bariatric surgery, respectively: Fasting, 105 (70 - 364) µg/dL and 198 (38 - 617) µg/dL; 1 hour, 103 (63 - 305) µg/dL and 160 (11 - 207) µg/dL; 2 hours, 103 (62 - 150) µg/dL and 141 (10 - 412) µg/dL; 3 hours. 97 (63 - 190) µg/dL and 153 (6 - 270) µg/dL; 4 hours, 91 (58 - 163) µg/dL and 156 (40 - 251) µg/dL (p>0.05), with no association of serum iron levels with time. There was a difference in total triglycerides (95 ± 29 mg/dL and 60 ± 10 mg/dL) which were correlated with a decrease in serum ferritin levels (r = 0,926, p = 0.008), UIBC (r = 0.910, p = 0.01), total cholesterol (r = 0,918, p = 0.01) and LDL-c fraction (r = 0.830, p = 0.04), with an increase in HDL-c fraction (r = 0,807, p = 0.05). CONCLUSION: Iron bioavailability in obese subjects was affected by the ingestion of the nutritional formulation containing calcium and fiber, a fact that may cause these patients to develop iron deficiency.

Objetivo: Obesos sometidos a cirugía bariátrica muestran la utilización de deterioro de hierro. Evaluar la biodisponibilidad del hierro en los obesos por el consumo de suplemento nutricional que contiene múltiples nutrientes antes y después de seis meses de la cirugía bariátrica. Material y Métodos: El estudio incluyó a 14 voluntarios antes y después de la cirugía bariátrica que recibieron formulaciones que contienen múltiples nutrientes y medir las concentraciones séricas de hierro en ayunas y cada 1 hora después de la ingestión de formulaciones, con un total de cuatro horas. Resultados: Ferremia por el consumo de entre dos formulaciones de pre-y post-operatorios fueron: El ayuno 104.50 (70,00-363,00) mg / dl y 198.00 (38.00 a 617.00) mg / dl, 103.00 horas (63,00 a 305,00) mg / dl y 160.00 (11,00- 206,90) mg / dL, 2 horas 102.50 (62.00 a 150.00) mg / dL y 141.30 (10.00 a 412.20) mg / dl, 3 horas 97.00 (63.00 a 190.00) mg mg / dl y 153,00 (6,00 hasta 269,60) / dl , 4 horas 91,00 (58,00 a 163,00) mg / dl y 156.10 (40.00 a 250.50) mg / dl y no hubo asociación estadísticamente significativa entre los dos períodos para los niveles de hierro suero. Los valores de la zona de las curvas en el suero fueron 453,50 ± 202,80 mg / dl / hora, p = 0,000 y 579,00 ± 380,30 mg / dl / hora, p = 0,007 y fue estadísticamente diferente entre los dos períodos. La biodisponibilidad del hierro en soluciones que contienen múltiples nutrientes se vio afectada antes y después de seis meses de la cirugía bariátrica. Conclusión: Se encontró que los niveles se redujeron ferremia con la cirugía, que puede poner en peligro estos pacientes presentaron deficiencia de hierro.

Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model.

The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompaniedby a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS.Levels of the inflammatory markers TNF-alpha and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.

AC biosusceptometry technique to evaluate the gastrointestinal transit of pellets under influence of prandial state.

Multiparticulate dosage forms have been proposed when distal regions of gastrointestinal tract are desirable as target of drugs. It is known that physiological parameters might interfere with the processes related to the drug delivery and absorption and therefore, it is essential to evaluate the behavior of such delivery systems in vivo. The aim of this study was to propose the AC Biosusceptometry technique as a noninvasive and radiation free device to evaluate the gastrointestinal transit of a magnetic multiparticulate dosage form in healthy volunteers under fasting and fed conditions. Magnetic pellets were prepared by the powder layering method of ferrite on nonpareils sugar beads and coated by using Eudragit. Our data showed that the AC Biosusceptometry technique was able to monitoring the gastrointestinal transit of pellets presenting similar profiles as demonstrated by standard techniques. Food intake has markedly influenced the gastric emptying as well as the colon arrival and the small intestine transit of magnetic pellets.

Mineral dialyzability in milk and fermented dairy products fortified with FeNaEDTA.

Iron, zinc, and calcium dialyzability and ascorbic acid (AA) concentrations were evaluated in milk and yogurt fortified with FeNaEDTA (FE) or ferrous sulfate (FS) as a control, with or without AA addition. The values obtained for FE iron dialyzability in milk were much higher than those obtained for FS. The addition of AA to milk improved Fe dialyzability when using FS and slightly decreased Fe dialyzability in the FE-fortified nonfermented samples. Milk fermentation increased iron availability from both iron sources. Zinc and calcium dialyzability in products containing any of the two iron sources was increased in fermented milks. EDTA improved Zn dialyzability from intrinsic zinc in every manufactured dairy product. Whereas for milks fortified with FS and stored at 4 degrees C for 24 h, the AA content remained close to the original concentration, a higher AA degradation was observed when milks were fortified with FE.

Electron paramagnetic resonance analyses of biotransformation reactions with cytochrome P-450 immobilized on mesoporous molecular sieves.

Mobil Crystalline Material (MCM-41) can be used for the immobilization of enzymes and the investigation of electron transfer in biological systems. Electron transfer between MCM-41 with aluminum (Al-MCM-41) and cytochrome P-450 (CYP2B4) was observed using electron paramagnetic resonance (EPR). When CYP2B4 was immobilized by adsorption, it catalyzed the conversion of aniline to p-aminophenol. The electron transfer was evidenced when the signal with a g value (also called g-factor or spectroscopic manifestation of the magnetic moment) of 1.98 increased at the same time that the signal with a g value 2.24 decreased due to the addition of NADPH to CYP2B4 immobilized on Al-MCM-41, indicating that FeIII was reduced to FeII. Therefore, it is possible that Al-MCM-41 participates in the electron transfer process in biological systems.

Bioavailability of Petit-Suisse cheese as food vehicle for iron fortification estimated by the prophylactic method.

Microencapsulated ferrous sulfate (SFE-171) and ferric orthophosphate in Petit-Suisse cheese were examined for iron bioavailability by the prophylactic method. The iron sources were industrially added to different samples of Petit-Suisse cheese, which were mixed with other food components in our laboratory before use. A reference standard diet inclusive of nonmicroencapsulated ferrous sulfate and a control diet low in iron content were prepared in the laboratory. The final iron content in the fortified diets was approximately 15 mg Fe/kg diet. These diets were administered to weaning rats for 23 days. The iron bioavailability was evaluated as the ratio of iron incorporated into hemoglobin to oral iron intake, thereby being estimated as 62.6 +/- 8.8% for ferrous sulfate and 59.2 +/- 10.6% for SFE-171, which were significantly effective at p < 0.01 compared to 43.4 +/- 10.5% for ferric orthophosphate. It thus turned out that SFE-171 was stable through industrial processing with Petit-Suisse cheese as the food vehicle and served as an iron fortifier equal to ferrous sulfate in bioavailability.

Iron derivatives from casein hydrolysates as a potential source in the treatment of iron deficiency.

The properties of an Fe(3+)-peptide complex containing 5.6% Fe, obtained by the reaction of ferric chloride with an enzymatic hydrolysate of casein, are described. The major site of iron binding corresponds primarily to the carboxylate groups and to a lesser extent to the peptide bonds. The Fe(3+)-peptide complex is insoluble at acid pH and completely soluble at neutral to alkaline pH. When soluble, the Fe(3+) is tightly bound to the complex peptide mixture but can be displaced and complexed by a low molecular weight ligand such as cysteine. Its efficacy in relation to iron sulfate was compared in rats. Both iron sources were administrated in Milli-Q water by gastric gavage to male Wistar rats (180-200 g) after an 18 h fast with water ad libitum. Fe(3+) from the Fe(3+)-peptide complex was transferred to the blood in a dose-dependent manner (1-8 mg of Fe/kg), and the serum iron levels were significantly higher (p < 0.001) than in a similar group of rats treated with iron sulfate. In the comparative kinetics experiments, the rats received 4 mg of Fe/kg. Both iron sources presented maximum absorption, as indicated by the elevation of serum iron levels, 30 min after administration, and the AUC(0)(-->2h) of the Fe(3+)-peptide complex was significantly higher (p < 0.05) than that observed with iron sulfate. The simultaneous administration of free peptides (0-192 mg) with the Fe(3+)-peptide complex or iron sulfate did not modify the extent of absorption of iron from both sources, suggesting that the absorption is due to the complex formed and probably not to exchange reactions in the gastrointestinal tract. In the hemoglobin repletion experiments carried out on newly weaned rats with anemia induced by a low-iron diet, supplementation of the diet with the the Fe(3+)-peptide complex was as efficient as supplementation with iron sulfate in the conversion from diet to hemoglobin iron. These results, taken together, suggest that the Fe(3+)-peptide complex is a potential compound for use as an iron source in biological situations.

Absorption of unlabeled reduced iron of small particle size from a commercial source. A method to predict absorption of unlabeled iron compounds in humans

The absorption of a commercial brand of small-particle reduced iron was evaluated in 10 normal subjects. For each subject, the hemoglobin incorporation method was used to measure the true absorption of 60 mg of iron from either ferrous sulfate or ferric ammonium citrate. The iron tolerance test (ITT) was also studied for these two compounds and for reduced iron. This procedure consisted of measuring the area under the curve of plasma iron elevations at specified times for 6 hours, or the peak plasma iron, corrected by the plasma iron disappearance rate obtained from measuring plasma iron at specified times for 4 hours after the slow intravenous injection of 0.4 mg of iron as ferric citrate. Only the ITT was used to measure the absorption of 60 mg of reduced iron. Reference dose iron ascorbate absorption was measured in each subject. The absorption of ferric ammonium citrate and reduced iron was expressed as percent of dose and also as absorption percent of that of ferrous sulfate. Mean geometric "true absorptions" were 39.0 for reference dose, 10.4 for FeSO4 and 2.4 for ferric ammonium citrate. The later was 23 that of FeSO4. By ITT the mean geometric absorptions were 7.9, 3.7 and 3.2 for FeSO4, ferric ammonium citrate and reduced iron respectively, or 47 and 41 of that of FeSO4. We propose that the true absorption of the commercial brand of reduced iron tested was 20 that of FeSO4 based on the relation between the ITT results of reduced iron and the ITT and true absorption values of ferric ammonium citrate in relation to FeSO4. The use of this method for measuring absorption of unlabeled iron compounds is discussed.

Absorption of iron from unmodified maize and genetically altered, low-phytate maize fortified with ferrous sulfate or sodium iron EDTA.

BACKGROUND: Reducing the phytate content in grains by genetic manipulation is a novel approach to increasing nonheme-iron absorption from mixed diets. Fractional iron absorption from a genetically modified strain of low-phytate maize (LPM) increased significantly, by 50%. OBJECTIVE: We assessed iron absorption from porridges prepared from the same LPM (lpa-1-1 mutant) and unmodified wild-type maize (WTM), both of which were fortified with either ferrous sulfate or sodium iron EDTA. DESIGN: Porridges providing 3.4 mg Fe were fortified with either ferrous sulfate or sodium iron EDTA to provide an additional 1 mg Fe/serving. In 14 nonanemic women, iron absorption was measured as the amount of radioiron incorporated into red blood cells (extrinsic tag method) 12 d after consumption of the study diets. RESULTS: No significant effect of phytate content on iron absorption was found when porridge was fortified with either sodium iron EDTA or ferrous sulfate. Fractional absorption of iron from WTM porridge fortified with sodium iron EDTA (5.73%) was 3.39 times greater than that from the same porridge fortified with ferrous sulfate (1.69%). Fractional absorption of iron from the sodium iron EDTA-fortified LPM porridge (5.40%) was 2.82 times greater than that from LPM porridge fortified with ferrous sulfate (1.91%) (P<0.0001 for both comparisons, repeated-measures analysis of variance). Thus, the previously identified benefit of LPM was no longer detectable when maize porridge was fortified with additional iron. CONCLUSION: Iron was absorbed more efficiently when the fortificant was sodium iron EDTA rather than ferrous sulfate, regardless of the type of maize.

Absorption of unlabeled reduced iron of small particle size from a commercial source. A method to predict absorption of unlabeled iron compounds in humans.

The absorption of a commercial brand of small-particle reduced iron was evaluated in 10 normal subjects. For each subject, the hemoglobin incorporation method was used to measure the true absorption of 60 mg of iron from either ferrous sulfate or ferric ammonium citrate. The iron tolerance test (ITT) was also studied for these two compounds and for reduced iron. This procedure consisted of measuring the area under the curve of plasma iron elevations at specified times for 6 hours, or the peak plasma iron, corrected by the plasma iron disappearance rate obtained from measuring plasma iron at specified times for 4 hours after the slow intravenous injection of 0.4 mg of iron as ferric citrate. Only the ITT was used to measure the absorption of 60 mg of reduced iron. Reference dose iron ascorbate absorption was measured in each subject. The absorption of ferric ammonium citrate and reduced iron was expressed as percent of dose and also as absorption percent of that of ferrous sulfate. Mean % geometric "true absorptions" were 39.0 for reference dose, 10.4 for FeSO4 and 2.4 for ferric ammonium citrate. The later was 23% that of FeSO4. By ITT the mean geometric % absorptions were 7.9, 3.7 and 3.2 for FeSO4, ferric ammonium citrate and reduced iron respectively, or 47 and 41% of that of FeSO4. We propose that the true absorption of the commercial brand of reduced iron tested was 20% that of FeSO4 based on the relation between the ITT results of reduced iron and the ITT and true absorption values of ferric ammonium citrate in relation to FeSO4. The use of this method for measuring absorption of unlabeled iron compounds is discussed.