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PubMed1999

Pharmacokinetics and red cell utilization of iron(III) hydroxide-sucrose complex in anaemic patients: a study using positron emission tomography.

The pharmacokinetics of a single intravenous injection of 100 mg iron hydroxide-sucrose complex labelled with a tracer in the form of 52Fe/59Fe was followed in six anaemic patients for a period ranging from 6 to 8 3 h using positron emission tomography (PET). Red cell utilization of the labelled iron was followed for 4 weeks. PET data showed radioactive uptake by the liver, spleen and bone marrow. The uptake by the macrophage-rich spleen demonstrated the reticuloendothelial uptake of this iron preparation, with subsequent effective release of that iron for marrow utilization. Red cell utilization, followed for 4 weeks, ranged from 59% to 97%. The bone marrow influx rate constant was independent of blood iron concentration, indicating non-saturation of the transport system in bone marrow. This implied that higher doses of the iron complex can probably be used in the same setting. A higher influx rate into the marrow compared with the liver seemed to be consistent with higher red cell utilization. This would indicate that early distribution of the injected iron complex may predict the long-term utilization.

Adult↗
PubMed1975

In vitro stimulation of apoferritin synthesis by iron.

The apparent induction of apoferritin synthesis by iron has been examined in cell-free systems from rat and rabbit liver. Both systems allowed the complete synthesis de novo of apoferritin isolated by chromatographic or immunological means. Addition of iron at levels of 0.2--1 mM specifically stimulated incorporation of radioactive amino acids into apoferritin purified after classical heat extraction. The effect was also observed when iron was added at the end of the incubation period in the absence of continuing protein synthesis. Further, iron addition had no effect on the amount of newly synthesised apoferritin subunits as estimated by direct immunological precipitation from the reaction mixture. These results suggest that iron acts at some stage subsequent to translation in stimulating apoferritin biosynthesis.

Animals↗
PubMed2005

Naturally occurring radioactive material (NORM) from a former phosphoric acid processing plant.

In recent years there has been an increasing awareness of the radiological impact of non-nuclear industries that extract and/or process ores and minerals containing naturally occurring radioactive material (NORM). These industrial activities may result in significant radioactive contamination of (by-) products, wastes and plant installations. In this study, scale samples were collected from a decommissioned phosphoric acid processing plant. To determine the nature and concentration of NORM retained in pipe-work and associated process plant, four main areas of the site were investigated: (1) the 'Green Acid Plant', where crude acid was concentrated; (2) the green acid storage tanks; (3) the Purified White Acid (PWA) plant, where inorganic impurities were removed; and (4) the solid waste, disposed of on-site as landfill. The scale samples predominantly comprise the following: fluorides (e.g. ralstonite); calcium sulphate (e.g. gypsum); and an assemblage of mixed fluorides and phosphates (e.g. iron fluoride hydrate, calcium phosphate), respectively. The radioactive inventory is dominated by 238U and its decay chain products, and significant fractionation along the series occurs. Compared to the feedstock ore, elevated concentrations (< or =8.8 Bq/g) of 238U were found to be retained in installations where the process stream was rich in fluorides and phosphates. In addition, enriched levels (< or =11 Bq/g) of 226Ra were found in association with precipitates of calcium sulphate. Water extraction tests indicate that many of the scales and waste contain significantly soluble materials and readily release radioactivity into solution.

Calcium Sulfate↗
PubMed1990

Iron retention by rats from casein-legume test meals: effect of tannin level and previous diet.

The effect of tannin content on iron (Fe) bioavailability from several legumes was evaluated. Absorption of Fe from a casein (C), isolated soy protein (ISP), chickpea (CP) or red kidney bean (RKB) test meal was tested in marginally Fe-deficient rats [9.9 +/- 0.2 g Hb/100 mL (mean +/- SD)] using the extrinsic tag technique. Also, the effects of a casein habitual diet or of one of three casein-legume habitual diets fed before and after the test meal were investigated. Weanling male rats were fed the habitual diets containing 23 +/- 4 mg Fe/kg of diet (range 17-28) for 13 d. On d 14, after an overnight fast, rats were fed the test meal (1.5 g + 0.1 microCi 59Fe), and whole-body radioactivity was determined. The same habitual diet was refed for seven additional days, and whole-body radioactivity was determined again. Rats retained more iron from C (86%) than from ISP, CP or RKB test meals (73%, 75% and 67%, respectively) when the respective casein-legume habitual diets were fed before and after the test meals. With the casein habitual diet, there was no difference in retained iron from C, ISP, CP or RKB test meals (86%, 87%, 83% and 82%, respectively). Retention of iron from an RKB test meal was increased from 69.6 to 73% when about 90% of the extractable tannins were removed, but the difference was not statistically significant. Thus, feeding a casein-legume diet but not a casein diet prior to a test meal apparently predisposes the rat to lower iron absorption. However, in these studies, tannins per se did not significantly depress iron bioavailability.

Absorption↗
PubMed2000

Involvement of iron (ferric) reduction in the iron absorption mechanism of a trivalent iron-protein complex (iron protein succinylate).

Iron protein succinylate is a non-toxic therapeutic iron compound. We set out to characterise the structure of this compound and investigate the importance of digestion and intestinal reduction in determining absorption of the compound. The structure of the compound was investigated by variable temperature Mössbauer spectroscopy, molecular size determinations and kinetics of iron release by chelators. Intestinal uptake was determined with radioactive compound force fed to mice. Reduction of the compound was determined by in vitro incubation with intestinal fragments. The compound was found to contain only ferric iron, present as small particles including sizes below 10 nm. The iron was released rapidly to chelators. Digestion with trypsin reduced the molecular size of the compound. Intestinal absorption of the compound was inhibited by a ferrous chelator (ferrozine), indicating that reduction to ferrous iron may be important for absorption. The native compound was a poor substrate for duodenal reduction activity, but digestion with pepsin, followed by pancreatin, released soluble iron complexes with an increased reduction rate. We conclude that iron protein succinylate is absorbed by a mechanism involving digestion to release soluble, available ferric species which may be reduced at the mucosal surface to provide ferrous iron for membrane transport into enterocytes.

Animals↗
PubMed1984

Lung cancer in Swedish iron miners exposed to low doses of radon daughters.

In a retrospective study, we investigated lung-cancer mortality from 1951 to 1976 in 1415 Swedish iron miners exposed to short-lived radioactive daughters of radon gas at concentrations leading to annual doses close to the currently accepted occupational limit. Fifty deaths from lung cancer were observed, as compared with 12.8 expected; expected rates were determined by a smoking-specific analysis based on data from a random sample of the Swedish male population. Among nonsmokers 18 deaths were observed, as compared with 1.8 expected; among current smokers and recent exsmokers 32 deaths were observed and 11.0 were expected. The effects of smoking and exposure to alpha radiation from radon daughters were nearly additive. Comparison of lung-cancer risk coefficients from this study and from other cohort studies of underground miners showed good agreement. Exposure to radon daughters is a major medical problem is underground metal mining, but our results also indicate that exposure to radon daughters at home accounts for an appreciable number of cases of lung cancer in the general population.

Adult↗
PubMed1999

Expression of ferritin protein and subunit mRNAs in normal and iron deficient rat brain.

In non-neuronal tissue, ferritin subunit mRNAs are regulated by post-transcriptional mechanisms leading to decreased ferritin protein synthesis during iron deficiency. Biochemical studies have demonstrated that the cerebral ferritin concentration declines during iron deficiency, suggesting that expression of ferritin subunit mRNAs in the brain may be regulated by mechanisms similar to those of non-neuronal tissue. However, as ferritin expression has been only vaguely studied in brain, this hypothesis remains to be tested. We investigated the influence of dietary iron deficiency on the cellular distribution of ferritin protein using immunohistochemistry and H- and L-ferritin subunit mRNAs by non-radioactive in situ hybridization. Pregnant rats were subjected to an iron depleted diet (6.4 mg/kg) from the day of conception. Litters were kept on the same diet until euthanized at the postnatal age of 10 weeks. This treatment reduced brain iron levels from approximately 57 to 26 microgram/g. Reducing the iron stores reduced histochemical detectable iron and the expression of ferritin immunoreactivity in neurons, oligodendrocyte-like and microglia-like cells. In normal rats, H- and L-ferritin subunit mRNAs were expressed in virtually all neurons and non-neuronal cells. The cerebral expression of the ferritin subunit mRNAs was not affected by iron deficiency. The levels of ferritin subunit mRNAs in the brain were also unaltered from iron deficiency when examined by Northern blotting. In conclusion, brain levels of iron and ferritin protein are highly susceptible to dietary iron deficiency, whereas the cerebral expression of H- and L-ferritin subunit mRNAs remains unchanged.

Animals↗
PubMed1990

Modulators of macrophage transferrin or transferrin-like protein.

The effects of endotoxin or testosterone on the amount of transferrin 59Fe (or like protein) in the murine macrophages was investigated. The mouse peritoneal macrophages were laden with 59Fe tagged red cells following the injection of mice with either agent. After harvesting the cells, they were lysed and the transferrin iron was released with 40% trichloroacetic acid. The supernatant (extract transferrin iron) and the pellet (other iron proteins iron) were separated by centrifugation and their radioactivities counted. The results were expressed in percentage. The endotoxin group had a geometric mean of transferrin 59Fe of 0.14% compared to 0.28% for the control, p less than 0.001. The geometric mean for transferrin 59Fe of the testosterone treated group was 0.51% compared to 0.35% for the control, p less than 0.05. Therefore, the endotoxin seems to contract the transferrin pool whereas testosterone seems to expand it.

Animals↗
PubMed1972

The control of iron absorption by the gastrointestinal mucosal cell.

Gastrointestinal mucosal factors controlling rates of iron absorption were studied utilizing an in vivo closed duodenal loop technique. Cellular distribution of newly absorbed radioiron was identified by molecular sieve and iron-exchange chromatography of the mucosal cell supernate. In the normal animal, iron rapidly appeared in ferritin, and this fraction accounted for greater than 90% of mucosal supernatant radioactivity after 60 min absorption time. The nonferritin radioiron appeared to be unbound iron salts. In the presence of increased iron absorption induced by iron depletion or hemolysis, the major difference from the normal distribution pattern was an increase in the proportion and quantity of the free iron salts. Incorporation of newly absorbed iron into ferritin did not correlate with the rate of iron absorption. No evidence was found for a specific soluble iron-chelating molecule within the mucosal cell. The nonheme iron content of the mucosal supernates from iron-deficient and hemolyzing animals were significantly lower than in the normal animal.The data are consistent with hypotheses which suggest that iron absorption rates may be controlled in part by the rate of initial iron uptake by the mucosal cell and that a membrane transport mechanism exists which is modulated by the nonheme iron content of the mucosal cell or some portion thereof.

Animals↗
PubMed1991

A new role for the transferrin receptor in the release of iron from transferrin.

Iron removal by pyrophosphate from human serum diferric transferrin and the complex of transferrin with its receptor was studied in 0.05 M HEPES or MES buffers containing 0.1 M NaCl and 0.01 M CHAPS at 25 degrees C at pH 7.4, 6.4, and 5.6. At each pH, the concentration of pyrophosphate was adjusted to achieve rates of release amenable to study over a reasonable time course. Released iron was separated from protein-bound iron by poly(ethylene glycol) precipitation of aliquots drawn from the reaction mixture at various times during the course of a kinetic run. The amount of 59Fe label associated with the protein and pyrophosphate was determined from the radioactivity of precipitate and supernatant, respectively, in each aliquot. Iron removal of 0.05 M pyrophosphate at pH 7.4 from diferric transferrin bound to the receptor is considerably slower than that from free diferric transferrin, with observed pseudo-first-order rate constants of 0.020 and 0.191 min-1, respectively. For iron removal by 0.01 M pyrophosphate at pH 6.4, corresponding rate constants are 0.031 and 0.644 min-1. However, at pH 5.6, iron removal by 0.001 M pyrophosphate is faster from diferric transferrin bound to its receptor than from free transferrin (observed rate constants of 0.819 and 0.160 min-1, respectively). Thus, the transferrin receptor not only facilitates the removal of iron from diferric transferrin at the low pH that prevails in endocytic vesicles but may also reduce its accessibility to iron acceptors at extracellular pH, thereby minimizing the likelihood of nonspecific release of iron from transferrin at the cell surface.

Cell Compartmentation↗
PubMed1979

[Study on decontamination of radioactive ruthenium by steel wool in waste solution (author's transl)].

Tracer experiments were done in order to establish a decontamination process of 106Ru in radioactive waste solution by column method paying special attention on the solution of nitratonitrosyl complex of Ru which is often encountered as a low level radioactive waste solution. It turned out that metallic iron was the most effective decontaminating agent among the several tens of materials tested. The decontamination factor (DF) of 106Ru increased in proportion to the total surface area of iron and it sensitively depended on the oxidation state of the surface as revealed by the batchwise and columnwise tests. Iron samples with high corrosiveness gave a much larger DF than those with low corrosiveness. The decontamination process proceeded as iron was being oxidized via Fe(metal)leads toFe(II)leads toFe(III). As the results, the DF initially increased after initiating the passage of water through the column but it then decreased as the oxidation process became inactive. An excellent durability up to 10000 bed volumes was demonstrated by the column method at a high average DF of 150.

Alloys↗
PubMed2003

Incorporation of iron into Tritrichomonas foetus cell compartments reveals ferredoxin as a major iron-binding protein in hydrogenosomes.

The intracellular transport of iron and its incorporation into organelles are poorly understood processes in eukaryotes and virtually unknown in parasitic protists. The transport of iron is of particular interest in trichomonads, which possess hydrogenosomes instead of mitochondria. The metabolic functions of hydrogenosomes, which contain a specific set of FeS proteins, entirely depend on iron acquisition. In this work the incorporation of iron into the cattle parasite Tritrichomonas foetus was monitored. Iron was efficiently taken up from (59)Fe-nitrilotriacetic acid and accumulated in the cytosol (88.9 %) and hydrogenosomes (4.7 % of the total radioactivity). Using atomic absorption spectrophotometry, an unusually high steady-state iron concentration in hydrogenosomes was determined [54.4+/-1.1 nmol Fe (mg protein)(-1)]. The concentration of iron in the cytosol was 13.4+/-0.5 nmol Fe (mg protein)(-1). Qualitative analysis of incorporated iron was performed using native gradient PAGE. The majority of the (59)Fe in the cytosol appeared as the labile-iron pool, which represents weakly bound iron associated with compounds of molecular mass ranging from 5000 to 30000 Da. Ferritin was not observed in Tt. foetus, nor in two other anaerobic protists, Entamoeba histolytica and Giardia intestinalis. Analysis of Tt. foetus hydrogenosomes showed at least nine iron-binding compounds, which were absent in metronidazole-resistant mutants. The major iron-binding compound was identified as [2Fe-2S] ferredoxin of the adrenodoxin type.

Amino Acid Sequence↗
PubMed1976

Gastrointestinal metabolism of cadmium in experimental iron deficiency;.

The average gastrointestinal uptake 4 h after an intragastric dose of 400 nmol of cadmium chloride labeled with 109CdCl2 in iron-deficient mice, 25%, was significantly greater than the result, 16%, in iron-normal animals, and more cadmium entered the body of the former, 3.8%, than the latter, 2% (P less than 0.05). Between 4 and 72 h, gastrointestinal radioactivity declined without further increase in body activity; however, more radiocadmium remained in the duodenum of iron-deficient than iron-normal animals (P less than 0.05). The radiocadmium sequestered in the duodenum was bound to a protein with a molecular weight of about 12,000. After subcutaneous injection of radiocadmium, the rate of excretion of radioactivity from the body was similar in iron-normal and iron-deficient mice; however, a greater proportion of the injected dose accumulated in the duodenum of the iron-deficient animals (P less than 0.05). Thus, the intestinal adapative response to iron deficiency may enhance cadmium toxicity, whereas sequestration and subsequent excretion of cadmium by the intestinal mucosa serves to protect the body against toxic effects. The duodenum, particularly in iron-deficient mice, is especially vulnerable to the toxic effects of cadmium.

Animals↗
PubMed1988

Glucose uptake and iron absorption by an isolated, vascularly and luminally perfused preparation of rat small intestine.

Some characteristics of an isolated vascularly and luminally perfused rat intestinal preparation are described. Over 60 to 90 min perfusion, the vascular perfusion medium (VPM) 'arterial' pressure remained stable and between animals it varied between 22 and 47 mmHg while the VPM flow rate remained constant at 1.3 ml/min. Hypersecretion, as monitored by changes in the concentration of phenol red in the luminal perfusion medium (LPM), did not generally occur. Histological examination of the tissue post-perfusion showed that normal morphology was retained for at least 1 h. Total glucose uptake ranged between 85 and 155 mumol/(g dry wt. h) with greater uptake from the VPM than the LPM. Approximately 50% of the glucose taken up by the intestine appeared as lactate in the perfusion media, most of which was released to the VPM. The addition of phloridzin (5 x 10(-4) M) to the LPM significantly reduced the uptake of glucose from the LPM and its transfer to the VPM. Iron absorption was studied by adding FeCl2 (with 59Fe and ascorbate, 100 micrograms/ml) to the LPM to give a final concentration of 10-100 micrograms iron/ml. The appearance of iron in the VPM was investigated over a period of 1 h. At the two lowest concentrations (10 and 25 micrograms/ml) there was a lag of 20-40 min before iron appeared in the VPM. At the higher doses (50 and 100 micrograms/ml) the lag was 10 min. During the final 20 min the appearance of iron in the VPM plateaued to dose-dependent constant rates. The ratio of the specific radioactivity of 59Fe in the two perfusates (LPM:VPM) was unity when the initial iron concentration was 25 micrograms/ml or above. At the lowest dose (10 micrograms/ml) this ratio was 2.5 indicating that during transfer, iron taken up from the LPM had mixed with a small labile endogenous iron pool. Both amounts of iron retained by the intestinal tissue and transferred to the VPM increased exponentially with increasing luminal iron dose. The amount of iron retained by the tissue was always greater than that transferred to the VPM.

Animals↗
PubMed1978

Inorganic iron absorption in subjects with iron deficiency anemia, achylia gastrica and alcoholic cirhosis using a whole-body counter.

A precise although technically complicated method is described for the estimation of iron absorption. A steel chamber is used to measure the total radioactivity of the patients. A dose of 59Fe is administered orally and the retention of radioactivity is measured on the 14th day, this amount being equivalent to the amount absorbed. In our male group, the mean absorption of inorganic iron was 22.5 +/- 8%, and in females it was 43.3 +/- 11%. In 10 patients with iron deficiency anemia, the mean was 92.2 +/- 6% , in 10 with gastric achylia it was 4.6 +/- 4%, and in 12 chronic alcoholics a value of 13.9 +/- 7% was found.

Absorption↗
PubMed2005

Recent results from a study of thorium lung burdens and health effects among miners in China.

The purpose of this study was to obtain more information about health effects among the dust-exposed male miners of Bayun Obo Rare-Earth and Iron Mine, China. From 2,390 male miners from the seven dust-generating workshops of the mine, 136 dust-exposed miners were randomly selected for study. Of these, 64 men were from the high-dust-generating workshop and 72 from the lower-dust-generating workshops; the latter group was used as an internal control. Physical measurements and medical examinations were carried out on each of these 136 men. The average measured thorium lung burden for the high-dust-exposure miners was significantly greater than that for the group of lower-exposure miners, and the incidence of severe breathlessness and pneumoconiosis of stage 0(+) was also significantly raised in the high-exposure group relative to the low-exposure group. An epidemiological study of lung cancer mortality among all the miners and staff of this mine was also carried out. This showed significantly raised levels of lung cancer mortality in both exposed miners and unexposed workers when compared with the Chinese population, and the level in exposed miners was significantly higher than that in unexposed men. The general high rate of lung cancer mortality in the workers of the mine is attributed to high levels of cigarette smoking, and the raised rate in the exposed miners relative to the unexposed workers to inhalation of silica- and thorium-bearing dusts and thoron progeny.

Adult↗