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Iron absorption in gastric and duodenal pathology in patients with iron deficiency anaemias.

Absorption of radioactive iron was studied in 87 patients with different types of iron deficiency anaemias and in 23 healthy subjects. The subjects were given 1...2muci of radiactive iron in the form of FeSO4 together with 5 mg of nonradioactive iron as a carrier and 100 to 150 g of white bread, radioactivity on the whole body being studied with a big liquid scintillation counter 4 pi (BLSC-2). In clinical observations and in single experiments on volunteers there was no conformity of the values of absorption with the levels of acid-formation. But in the same time the gastric juice from an anaemic horse almost doubled iron absorption in healthy individuals. Marked morphological changes in the gastric mucosa inhibited the absorption in the intestine and the degree of increase of absorption in patients with anaemia depended to some extent on the morphological conditions of the gastric mucosa. When healthy subjects and patients with iron deficiency anaemia were given bread "enriched" with iron before baking instead of common bread with "external" mark there was observed similar correlation between the values of absorption but the figures were somewhat lower.

Anemia, Hypochromic↗

Iron delivery during proliferation and differentiation of kidney tubules.

Proliferation during kidney development can be stimulated with an iron chelator, ferric pyridoxal isonicotinoyl hydrazone (FePIH). Neither the starting products nor the intermediary in FePIH synthesis stimulated proliferation. Thus, the growth-promoting effects of FePIH are due to the iron ion. Some other low molecular weight, saturated iron chelators such as glycyl-histidyl-lysine acetate, nitrilotriacetic acid, ascorbate, citrate, and unchelated ferrous sulfate could not support as high a degree of proliferation as FePIH or transferrin. FePIH delivered just slightly less radioactive iron into the trichloroacetic acid-precipitable fraction than transferrin. The octanol/saline partition coefficients of radioactive iron in solution with transferrin, nitrilotriacetic acid, or chloride were all less than 0.06. Thus, these compounds cannot efficiently traverse the lipid membrane. On the other hand, Fe3+ carried by PIH had a partition coefficient of 0.96. Hence, FePIH can stimulate proliferation because it can carry iron through the lipid membrane. Transferrin is not lipophilic but it delivers iron by receptor-mediated endocytosis.

Animals↗

[Fe59 studies on the question of rabbit erythrocyte life-span].

The present paper demonstrates a method to separate red cells of different age. The erythrocytes were separated by ultracentrifugation. The validity of this method was examined with radioactive iron (59Fe). During seventy days kinetic studies were performed in liver and spleen. A body scan was used to distinguish liver and spleen by radioactive iron.

Animals↗

Cooperative erythropoietic assay of several steroid metabolites in polycythemic mice.

A blinded cooperative assay of several androstane and pregnane steroid metabolites has been carried out in order to determine whether 5beta-H derivatives are as active as testosterone in stimulating in vivo erythropoiesis. The steroids tested were: testosterone, 5alpha-dihydrotestosterone, 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-dihydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one. The incorporation of radioactive iron into newly formed red cells in exhypoxic polycythemic mice was used to compare the effects of the steroids. Testosterone and 5alpha-dihydrotestosterone both produced significant increases in 59Fe incorporation. 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-hydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one were all devoid of significant erythropoietic activity in polycythemic mice in almost all instances. Thus, under the conditions chosen, this study failed to demonstrate that 5beta-steroids increase radioactive iron incorporation in red cells of exhypoxic polycythemic mice.

Androstanes↗

Red cell kinetics in thalassaemia intermedia: its use for a prospective prognosis.

A kinetic study of erythroid cell production and destruction (radioactive iron incorporation, red blood cell survival time, bone marrow scintigraphy) was performed in 12 cases of thalassaemia intermedia (six adults and six children), classified retrospectively, and compared to that performed in 17 cases of Cooley's anaemia. Our results confirm the genetic heterogeneity of these cases, the level of Hb F varies from 30% to 100% and the non alpha/alpha chain synthesis is only statistically superior to that seen in Cooley's disease. On the other hand, the kinetic study clearly separates the cases who are, or will be, clinically intermediate, showing a higher radioactive iron medullary uptake, a less ineffective erythropoiesis than that seen in Cooley's disease, and a greater peripheral haemolysis. In our study, no overlap was seen between the two groups. Iron kinetic study is then of prognostic interest and may help in therapy decisions, transfusion regimen and iron chelation, and splenectomy.

Adolescent↗

Geophagia in Turkey: iron and zinc deficiency, iron and zinc absorption studies and response to treatment with zinc in geophagia cases.

A brief summary of the research carried out on the problem of geophagia is reported in this paper. Geophagia was a common finding among Turkish children and women in villages, associated with severe iron deficiency anemia in addition to zinc depletion. The syndrome characterized by geophagia, iron deficiency anemia, growth retardation, hypogonadism and zinc deficiency has been observed in both sexes in Turkey for several decades. Zinc deficiency has been also shown by our group in this syndrome. The decreased concentrations of zinc in serum, plasma, RBC, hair and urine were measured by atomic absorption spectrophotometer. Oral iron (both inorganic and radioactive iron) and zinc absorption tests were carried out with and without clay and revealed decreased iron and zinc absorption in some cases with prolonged geophagia. Therefore, malabsorption of iron and zinc was considered to be an additional and/or a new finding in the syndrome. Furthermore, Turkish clay most probably inhibits zinc absorption in a way similar to its inhibition of iron absorption. It was worthy of observation that some Turkish patients with this syndrome had a thalassemia-like appearance with similar skull-bone changes. Finally, growth retardation and delayed puberty were shown to be corrected by oral zinc treatment for 6-month terms. Linear growth and sexual maturation were found to be greater in the zinc-treated group than in the controls.

Adolescent↗

Ribosomal protein P2, a novel iron-binding protein.

We examined the properties of a new iron-binding protein purified previously from rat liver (T. Furukawa, S. Taketani, H. Kohno, and R. Tokunaga, 1991, Biochem. Biophys. Res. Commun. 181, 409-415). The protein was digested with trypsin and the peptides were analyzed by reverse-phase high-performance liquid chromatography. The partial amino acid sequences of the tryptic peptides coincided with that of rat ribosomal protein P2. Immunoblot analysis and iron-binding assay confirmed that the iron-binding protein and ribosomal protein P2 are identical. Then the iron binding ability of ribosomal protein P2 was examined in rat hepatoma H4IIEC3 cells incubated with radioactive iron. When immunoprecipitation with anti-iron-binding protein serum was performed using cells incubated with 59Fe-citrate, about 4% of the 59Fe radioactivity in cells was associated with the iron-binding protein through 30 to 90 min of incubation. About 1.5% of radioactive iron in cells incubated with 59Fe-transferrin was found in immunoprecipitates with anti-iron-binding protein serum during 1 to 5 h of incubation, and 4 to 7% of the radioactivity was found in immunoprecipitates with a monoclonal antibody against ribosomal P proteins in the same incubation. These results demonstrate that ribosomal proteins P2 binds iron taken up by the cells.

Amino Acid Sequence↗

Non-random distribution of iron entering rat liver ferritin in vivo.

Radioactive iron incorporated into rat liver ferritin in vivo and then released in vitro up to 24h after injection follows 'last-in-first-out' behaviour. Thus, within this period at least, the added iron does not equilibrate with iron already present in the molecule's iron-core.

Animals↗

HUMAN BONE MARROW DISTRIBUTION SHOWN IN VIVO BY IRON-52 AND THE POSITRON SCINTILLATION CAMERA.

Radioactive iron, which concentrates in erythropoietic marrow, is given intravenously, and 16 hours later pictures of its distribution are taken with the positron camera. The instrument is an imaging device that produces pictures of the distribution of positron-emitting nuclides without scanning. Wide variations in the distribution of marrow are found in various diseases.

Biomedical Research↗

Iron availability from meat.

1. The distribution of radioactive iron in 59Fe-labelled rat muscle extract was determined using gel filtration. This showed that most (approximately 70%) of the radioactivity was associated with the heamatin compounds; myoglobin and haemoglobin. 2. Raw beef and freeze-dried rat muscle were digested in vitro, under simulated physiological conditions, and after centrifugation the supernatants fractionated by gel filtration. The soluble products were haematin Fe complexes of molecular weight above 10,000 and non-haematin Fe compounds of molecular weight below 6000, the major products being the non-haematin Fe complexes. The soluble compounds were also separated by dialysis and, in rat muscle, it was found that the low-molecular-weight non-haematin compounds accounted for more than 80% of the total soluble iron. 3. In vivo absorption studies with rats showed the Fe in a digested muscle dialysate to be more readily absorbed than that from an aqueous muscle extract which itself was more readily absorbed than the Fe from whole blood. 4. It may not, therefore, be the haemoproteins per se which are responsible for the high availability of Fe in meat, but rather the nature of their degradation products, formed by digestion within the meat environment.

Animals↗

Plasma iron and saturation of plasma iron-binding protein in dogs as related to the gastro-intestinal absorption of radioiron.

The absorption of a test amount of radioactive iron during artificial saturation of the plasma iron-binding protein, by the repeated intravenous injection of small amounts of iron, was measured in three normal and four anemic dogs. The procedure had no detectable influence on the iron absorption of the normal dogs nor on that of two of the anemic dogs. Two other anemic dogs showed some suppression of iron absorption, though the amount absorbed was still in excess of that absorbed by a normal dog. The reasons for this suppression are not clear from these experiments. Artificially raising the plasma iron to normal levels in one anemic dog did not influence the absorption of iron from the gastrointestinal tract nor was a delayed effect noted after the plasma iron had fallen to base line levels after 5 hours of artificial saturation. It appears that the plasma iron-binding protein and its relative saturation play little role per se in the control of iron absorption in dogs.

Anemia↗

Iron absorption in experimental uremia.

Gastrointestinal absorption of radioactive iron (59Fe) was studied in uremic rats. Duodenal gut sac transport of 59Fe in a group of 12 rats with a mean BUN of 98+/-24.4 mg%, was 2.29+/-1.16. This was significantly lower (p less than 0.01) than the amount of 59Fe transported (4.88+/-1.87) across the duodenum of a group of control rats, mean BUN 22.9+/-3.2 mg%. We conclude that there is diminished absorption of iron in uremia.

Animals↗

Hydroxamate recognition during iron transport from hydroxamate-ion chelates.

Kinetics of radioactive iron transport from three structurally different secondary hydroxamate-iron chelates (schizokinen-iron, produced by Bacillus megaterium ATCC 19213; Desferal-iron, produced by an actinomycete; and aerobactin-iron, produced by Aerobacter aerogenes 62-1) revealed that B. megaterium SK11 (a mutant which cannot synthesize schizokinen) has a specific transport system for utilization of ferric hydroxamates with a recognition capacity based on the chemical structure of the hydroxamate. Both Desferal and schizokinen enhanced iron uptake in this organism; however, Desferal-iron delivered only one-sixth the level of iron incorporated from the schizokinen-iron chelate. Desferal-iron did not generate the rapid rates of iron transport noted with schizokinen-iron at elevated iron concentrations. Assays containing large excesses of either iron-free Desferal or iron-free schizokinen suggested that the iron-free hydroxamate may compete with the ferric hydroxamate for acceptance by the transport system although the system has greater affinity for the iron chelate. Aerobactin-iron did not stimulate iron uptake in B. megaterium SK11 and aerobactin inhibited growth of this organism, indicating that B. megaterium SK11 cannot efficiently process the aerobactin-iron chelate.

Bacillus megaterium↗

Active transport of iron in Bacillus megaterium: role of secondary hydroxamic acids.

Kinetics of radioactive iron transport were examined in three strains of Bacillus megaterium. In strain ATCC 19213, which secretes the ferric-chelating secondary hydroxamic acid schizokinen, (59)Fe(3+) uptake from (59)FeCl(3) or the ferric hydroxamate Desferal-(59)Fe(3+) was rapid and reached saturation within 3 min. In strain SK11, which does not secrete schizokinen, transport from (59)FeCl(3) was markedly reduced; the two ferric hydroxamates Desferal-(59)Fe(3+) or schizokinen-(59)Fe(3+) increased both total (59)Fe(3+) uptake and the (59)Fe(3+) appearing in a cellular trichloroacetic acid-insoluble fraction, although 10 min was required to reach saturation. Certain characteristics of transport from both ferric hydroxamates and FeCl(3) suggest that iron uptake was an active process. The growth-inhibitory effect of aluminum on strain SK11 was probably due to the formation of nonutilizable iron-aluminum complexes which blocked uptake from (59)FeCl(3). Desferal or schizokinen prevented this blockage. A strain (ARD-1) resistant to the ferric hydroxamate antibiotic A22765 was isolated from strain SK11. Strain ARD-1 failed to grow with Desferal-Fe(3+) as an iron source, and it was unable to incorporate (59)Fe(3+) from this source. Growth and iron uptake in strain ARD-1 were similar to strain SK11 with schizokinen-Fe(3+) or the iron salt as sources. It is suggested that the ferric hydroxamates, or the iron they chelate, may be transported by a special system which might be selective for certain ferric hydroxamates. Strain ARD-1 may be unable to recognize both the antibiotic A22765 and the structurally similar chelate Desferal-Fe(3+), while retaining its capacity to utilize schizokinen-Fe(3+).

Aluminum↗

Effects of the pyrones, maltol and ethyl maltol, on iron absorption from the rat small intestine.

The pyrones, 3-hydroxy-2-methyl-4-pyrone (maltol) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol) chelate iron with a high affinity and selectivity. The resulting 1:3 (metal-ligand) complexes, being neutral, are able to partition readily across cell membranes and thus may facilitate iron transport across the intestinal wall. Absorption of radioactive iron (59Fe) in the presence of these pyrones was investigated in male rats 1, 2, 4 and 6 h after intraduodenal administration of a 7 micrograms dose and compared with that of 59Fe given as the sulphate, gluconate, fumarate or complexed to EDTA. Total body absorption and distribution were calculated from the 59Fe content of various tissue samples. With all the iron preparations used, blood levels of 59Fe were highest 1 h after injection whilst the 59Fe content at the major site of deposition, i.e. the bone marrow, increased up to 6 h. No 59Fe was found in the urine. Total body absorption of 59Fe was significantly higher from the pyrones than from the other four preparations. Over the dose range 0.7-700 micrograms, the proportion of 59Fe absorbed from both iron maltol and iron sulphate decreased with increasing dose. Enhanced 59Fe uptake from maltol was evident at 0.7-70 micrograms but not at 700 micrograms suggesting that use of these pyrones will not result in iron overload. Absorption of 59Fe given into the stomach was slower in onset but was sustained longer presumably via a steady delivery of iron to the duodenum from the gastric reservoir.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Application of magnetic sector thermal ionization mass spectrometry to studies of erythrocyte iron incorporation in small children.

The optimal evaluation of iron metabolism requires the administration of two isotopes of iron. However, high-precision measurement of isotopic ratios from blood samples obtained after administration of two stable isotopes of iron to human subjects has not previously been reported. Using a cation-exchange system to isolate iron from blood samples, we found that high-precision (< 0.2%) measurements of 58Fe/56Fe and 57Fe/56Fe could be performed using magnetic sector thermal ionization mass spectrometry. Clinical studies in four 1-year-old infants showed that this technique could be used to demonstrate a lower rate of iron absorption in small children given an iron supplement (57Fe) with milk compared to those given iron (58Fe and ferrous sulfate) with ascorbic acid. This technique will enable the evaluation of iron metabolism in populations in whom the use of radioactive iron tracers is not appropriate.

Adolescent↗

Iron absorption by humans from hemosiderin and ferritin, further studies.

Iron absorption from hemosiderin and ferritin biosynthetically labeled with radioactive iron has been studied in 61 subjects. The geometrical mean iron absorption from hemosiderin in both normal and iron deficient subjects was 3.4%. Its mean absorption ranged from 1.9% in normal subjects to 4.7% in subjects with moderate iron deficiency and 7.3% in subjects with marked iron deficiency. The iron absorption from hemosiderin was markedly increased when it was administered with ascorbic acid or liver. The absorption of iron from hemosiderin when hemosiderin and wheat were consumed in a meal, was lower than the absorption from wheat. Iron from liver ferritin and liver hemosiderin were less absorbed in this study than that previously reported for liver hemoglobin. The studies presented here support the possibility that ferritin and hemosiderin form an iron pool different from the non-heme pool formed by vegetal iron, egg iron and ferric and ferrous salts.

Absorption↗