Criticality of Surface Characteristics of Intravenous Iron-Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics.

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.

Iron Fortification Practices and Implications for Iron Addition to Salt.

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.

In vitro and in vivo DFO-chelatable labile iron release profiles among commercially available intravenous iron nanoparticle formulations.

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.

Sorptive equilibrium profile of fluoride onto aluminum olivine [(FexMg1-x)2SiO4] composite (AOC): Physicochemical insights and isotherm modeling by non-linear least squares regression and a novel neural-network-based method.

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.

Bioaccessibility of arsenic in mining-impacted circumneutral river floodplain soils.

Floodplain soils are frequently contaminated with metal(loid)s due to present or historic mining, but data on the bioaccessibility (BA) of contaminants in these periodically flooded soils are scarce. Therefore, we studied the speciation of As and Fe in eight As-contaminated circumneutral floodplain soils (≤ 21600 mg As/kg) and their size fractions using X-ray absorption spectroscopy (XAS) and examined the BA of As in the solids by in-vitro gastrointestinal (IVG) extractions. Arsenopyrite and As(V)-adsorbed ferrihydrite were identified by XAS as the predominant As species. The latter was the major source for bioaccessible As, which accounted for 5-35% of the total As. The amount of bioaccessible As increased with decreasing particle size and was controlled by the slow dissolution kinetics of ferrihydrite in the gastric environment (pH 1.8). The relative BA of As (% of total) decreased with decreasing particle size only in a highly As-contaminated soil--which supported by Fe XAS--suggests the formation of As-rich hydrous ferric oxides in the gastric extracts. Multiple linear regression analyses identified Al, total As, C(org), and P as main predictors for the absolute BA of As (adjusted R(2) ≤ 0.977). Health risk assessments for residential adults showed that (i) nearly half of the bulk soils may cause adverse health effects and (ii) particles <5 µm pose the highest absolute health threat upon incidental soil ingestion. Owing to their low abundance, however, health risks were primarily associated with particles in the 5-50 and 100-200 µm size ranges. These particles are easily mobilized from riverbanks during flooding events and dispersed within the floodplain or transported downstream.

[The specific features of copper and manganese metabolism in the use of iron-containing preparations].

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.

Revised recommendations for iron fortification of wheat flour and an evaluation of the expected impact of current national wheat flour fortification programs.

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.

The role of iron supplementation during epoietin treatment for cancer-related anemia.

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.

Relative oral bioavailability of arsenic from contaminated soils measured in the cynomolgus monkey.

A number of studies have found that gastrointestinal absorption of arsenic from soil is limited, indicating that a relative oral bioavailability (RBA) adjustment is warranted when calculating risks from exposure to arsenic-contaminated soil. However, few studies of arsenic bioavailability from soil have been conducted in animal models with phylogenetic similarity to humans, such as nonhuman primates. We report here the results of a study in which the RBA of arsenic in soil from a variety of types of contaminated sites was measured in male cynomolgus monkeys. A single oral dose of each contaminated soil was administered to five adult male cynomolgus monkeys by gavage, and the extent of oral absorption was evaluated through measurement of arsenic recovery in urine and feces. Urinary recovery of arsenic following doses of contaminated soil was compared with urinary recovery following oral administration of sodium arsenate in water in order to determine the RBA of each soil. RBA of arsenic in 14 soil samples from 12 different sites ranged from 0.05 to 0.31 (5-31%), with most RBA values in the 0.1-0.2 (10-20%) range. The RBA values were found to be inversely related to the amount of arsenic present with iron sulfate. No other significant correlations were observed between RBA and arsenic mineralogic phases in the test soils. The lack of clear relationships between arsenic mineralogy and RBA measured in vivo suggests that gastrointestinal absorption of arsenic from soil may be more complex than originally thought, and subject to factors other than simple dissolution behavior.

Iron enriched yeast biomass--a promising mineral feed supplement.

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.

Linking the bioavailability of iron compounds to the efficacy of iron-fortified foods.

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.

Iron absorption by healthy women is not associated with either serum or urinary prohepcidin.

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.

Reduction of nitrobenzene and formation of corrosion coatings in zerovalent iron systems.

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.

In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios.

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.

[Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs].

In the present study, we devised a simple method for detecting the drug interaction between oral iron preparations and phenolic hydroxyl group-containing drugs, using the coloring reaction as indicator, due to the formation of complexes or chelates. In the method, oral iron preparations and test drugs in amounts as much as single dose for adults were added to 10 ml of purified water to make sample suspensions for testing. Thirty minutes after mixing an oral iron suspension and a test drug suspension, the change of color in the mixture was observed macroscopically and graded as 0 to 3, with a marked color change judged as grade 3 and no color change as grade 0. Screening of 14 test drugs commonly used orally was carried out. When using sodium ferrous citrate preparations as oral iron, 5 were classified as grade 3, 2 as grade 2, 4 as grade 1, and 3 as grade 0, respectively. To verify usefulness of the method, the interactions suggested by screening were pharmacokinetically assessed by measuring serum concentrations of the drug in mice. When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a significant reduction in bioavailability of the test drug was observed, indicating possible drug interaction between the test drug and oral iron. Combined administration of an acetaminophen preparation, judged as grade 1, and oral iron preparation showed no influence on the bioavailability of the test drug, implying no detectable interactions between them. In conclusion, the simple method devised in the present study is useful for precognition of drug interactions between oral iron preparations and phenolic hydroxyl group-containing drugs, and the drugs with a higher grade in screening may induce drug interactions with oral iron.

Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.

The usefulness of elemental iron for cereal flour fortification: a SUSTAIN Task Force report. Sharing United States Technology to Aid in the Improvement of Nutrition.

Fortification of cereal flours may be a useful public health strategy to combat iron deficiency. Cereal flours that are used shortly after production (e.g., baking flour) can be fortified with soluble iron compounds, such as ferrous sulfate, whereas the majority of flours stored for longer periods is usually fortified with elemental iron powders to avoid unacceptable sensory changes. Elemental iron powders are less well absorbed than soluble iron compounds and they vary widely in their absorption depending on manufacturing method and physicochemical characteristics. Costs vary with powder type, but elemental iron powders are generally less expensive than ferrous sulfate. This review evaluates the usefulness of the different elemental iron powders based on results from in vitro studies, rat assays, human bioavailability studies, and efficacy studies monitoring iron status in human subjects. It concludes that, at the present time, only electrolytic iron powder can be recommended as an iron fortificant. Because it is only approximately half as well absorbed as ferrous sulfate, it should be added to provide double the amount of iron.

Superparamagnetic agents in magnetic resonance imaging: physicochemical characteristics and clinical applications. A review.

Superparamagnetic agents in magnetic resonance imaging: physico-chemical characteristics and clinical applications. Superparamagnetic agents have been the subject of extensive research over the last decade. They consist of iron oxide nanoparticles which are highly effective in Magnetic Resonance Imaging (MRI). The particle size varies widely and influences their physicochemical and pharmacokinetic properties. Their main present and future applications by the parenteral route are: imaging of gastrointestinal tract, liver and spleen, lymph nodes. Ultrasmall superparamagnetic iron oxide particles (USPIO) are also blood pool agents which could be used for perfusion imaging (i.e. brain or myocardial ischemic diseases) as well as for imaging of vessels in Magnetic Resonance Angiography. These agents open up an important field of research into more specific agents adapted to clinicians' needs in diagnostic imaging.

Effects of ascorbic acid on interactions between ciprofloxacin and ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate, in mice.

The absorption of ciprofloxacin has been reported to be impaired by concomitant administration of ferrous sulphate. The effects of sodium ferrous citrate and ferric pyrophosphate, which have been used as extensively as ferrous sulphate, on the absorption of ciprofloxacin were compared with that of ferrous sulphate. The effects of ascorbic acid on the interactions between ciprofloxacin and each iron compound were studied in mice. Mice were treated orally with ciprofloxacin (50 mg kg(-1)) alone, the iron compound (ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate; 50 mg elemental iron kg(-1)) alone, ciprofloxacin with each iron compound or ciprofloxacin in combination with each iron compound and ascorbic acid (250 mg kg(-1)). The maximum serum concentration of ciprofloxacin was significantly (P < 0.01) reduced from 1.15+/-0.11 microg mL(-1) (ciprofloxacin alone) to 0.17+/-0.01, 0.27+/-0.01 or 0.28+/-0.02 microg mL(-1), respectively, when ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate was administered along with ciprofloxacin. The addition of ascorbic acid did not affect the inhibitory effects of each iron compound on the absorption of ciprofloxacin. Ciprofloxacin did not affect the variation of serum iron levels after administration of each iron compound. The addition of ascorbic acid significantly (P < 0.01) enhanced the increase in serum iron concentration after administration of sodium ferrous citrate, showing an increase from 270+/-6 microg dL(-1) to 463+/-11 microg dL(-1) compared with an increase from 248+/-8 microg dL(-1) to 394+/-18 microg dL(-1) after administration of sodium ferrous citrate alone. Ascorbic acid also caused a significant (P < 0.01) increase in serum iron concentration from 261+/-16 microg dL(-1) to 360+/-12 microg dL(-1) after administration of ferric pyrophosphate, although it did not affect the levels after ferrous sulphate administration. The results suggest that sodium ferrous citrate and ferric pyrophosphate should not be administered with ciprofloxacin (as for ferrous sulphate) and that sodium ferrous citrate is converted to the ferric form more easily than ferrous sulphate. This difference in convertibility might contribute to a clinical difference between sodium ferrous citrate and ferrous sulphate.

Uptake of iron by a vegetable; kaiware daikon (Japanese radish sprout).

Uptake of iron and several other minerals into kaiware daikon (Japanese radish sprout) was investigated by changing their supplementary conditions. The supplementation of calcium sulfate (0.1% (w/v), 230 ppm as calcium ion) and iron (III) chloride (0.1% (w/v), 200 ppm as iron ion) in hydroponics promoted the growth of kaiware daikon ca. 1.0-1.5 cm longer than the control group of no additions, while magnesium sulfate (0.1% (w/ v), 100 ppm as magnesium ion) did not affect the length of sprouts so much, but caused their leaves to grow a little wider. Mineral contents in the sprout were maximal when it was added, at ca. 0.1% (w/v), to the hydroponic solution. In tests regarding iron (II) ion supplementation, the color of the kaiware daikon seeds changed from brownish to black and the sprout did not grow well. In contrast, the iron (III) ion did not affect their color and promoted growth of the sprout. When the seeds were soaked in an iron (II) sulfate (75 ppm) or an ammonium iron (III) citrate (180 ppm) solution for 24 h prior to germination, the resulting kaiware daikon contained a few times higher the amount of iron than commercially available ones.