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PubMed1976

Mineral imbalances in farm animals and their study and diagnosis with isotopic tracers.

Twenty-two mineral elements are known to be essential for animal life. These are calcium, phosphorus, sulphur, potassium, sodium, chlorine, magnesium, iron, iodine, copper, manganese, zinc, cobalt, molybdenum, selenium, chromium, tin, vanadium, fluorine, silicon, nickel and arsenic. Naturally occurring and man-made dietary imbalances of many of these elements and their interactions with other minerals are described and their functions and requirements by farm animals are outlined. The nature and importance of metabolic interactions among the mineral elements are discussed and the important concept stressed that there is no single minimum requirement or safe tolerance of a particular mineral, but a series of such minimum requirements and safe tolerances depending on the extent to which other minerals with which it interacts is present or absent from the diet. Radioactive tracer elements are shown to be of great value in the determination of mineral nutrient availability to the animal and for following mineral metabolic movements in the body. They are also shown to have considerable potential for the diagnosis of mineral imbalances. Various in vivo and in vitro techniques, involving both radioactive and stable tracers developed for the early diagnosis of mineral deficiencies are described and the strengths and weaknesses of such techniques in comparison with standard biochemical tests, are discussed. The need for further critical studies with isotopic tracers in the detection and diagnosis of mineral imbalances is emphasized. The main types of biochemical criteria used in the diagnosis of mineral deficiencies and excesses are given, with appropriate examples of their use.

Animals↗

PubMed1997

Manganese metabolism is impaired in the Belgrade laboratory rat.

Homozygous Belgrade rats have a hypochromic anaemia due to impaired iron transport across the cell membrane of immature erythroid cells. This study aimed at investigating whether there are also abnormalities of Mn metabolism in erythroid and other types of cells. The experiments were performed with homozygous (b/b) and heterozygous (+/b) Belgrade rats and Wistar rats and included measurements of Mn uptake by reticulocytes in vitro, Mn absorption from in situ closed loops of the duodenum, and plasma clearance and uptake by several organs after intravenous injection of radioactive Mn bound to transferrin (Tf) or mixed with serum. Similar measurements were made with 59Fe-labelled Fe in several of the experiments. Mn uptake by reticulocytes and absorption from the duodenum was impaired in b/b rats compared with +/b or Wistar rats. The plasma clearance of Mn-Tf was much slower than Mn-serum, but both were faster than the clearance of Fe-Tf. Uptake of 54Mn by the kidneys, brain and femurs was less in b/b than Wistar or /+b rats, but uptake by the liver was greater in b/n rats. Similar differences were found for 59Fe uptake by kidneys, brain and femurs but is concluded that the genetic abnormality present in b/b rats affects Mn metabolism as well as Fe metabolism and that Mn and Fe share similar transport mechanisms in the cells of erythroid tissue, duodenal mucosa, kidney and blood-brain barrier.

Absorption↗

PubMed1998

Characterisation of non-transferrin-bound iron (ferric citrate) uptake by rat hepatocytes in culture.

Under conditions of iron overload plasma transferrin can be fully saturated and the plasma can transport non-transferrin-bound Fe which is rapidly cleared by the liver. Much of this Fe is complexed by citrate. The aim of the present work was to characterise the mechanisms by which Fe-citrate is taken up by hepatocytes using a rat hepatocyte cell culture model. The cells, after one day in culture, were incubated with 59Fe-labelled Fe-citrate for varying time periods, then washed and Fe uptake to the membrane and intracellular compartments of the cell was determined by radioactivity measurements. Maximal rates of internalisation of Fe occurred at a Fe:citrate molar ratio of 1:100 or greater, a pH of approximately 7.4 and an extracellular Ca2+ concentration of 1.0 mM. Fe uptake showed Michaelis-Menten kinetics and was a temperature-dependent process. The K(m) and Vmax for Fe internalisation by the cells at 37 degrees C were approximately 7 microM and 2 nmol/mg DNA/min (25 x 10(6) atoms/cell/min), respectively; and the Arrhenius activation energy was 35 kJ/mol. The transition metals, Zn2+, Co2+ and Ni2+, inhibited Fe uptake when used at 10 and 100 times the concentration of Fe. The rate of Fe internalisation from Fe-citrate was found to be approximately 20 times as great as that from Fe-transferrin with Fe concentrations of 1 and 2.5 microM for both forms of Fe. The rate of Fe uptake by iron-loaded hepatocytes obtained from rats which had been fed carbonyl Fe was not significantly different from that by normal hepatocytes. These experiments show that rat hepatocytes in primary culture have a high capacity to take up non-transferrin-bound Fe in the form of Fe-citrate and that uptake occurs by facilitated diffusion. The iron transport process does not appear to be regulated by cellular Fe levels.

Animals↗

PubMed1982

Tropolone: a lipid solubilizing agent for cationic metals.

Lipid soluble agents which chelate radioactive cations have several potential uses in nuclear medicine including: brain imaging, labeling of blood elements, and identifying fatty infiltration of organs. A tropolone-gallium complex has been characterized by the determination of in vitro partition ratios correlated with in vivo organ distribution in the rat. Partition ratios were determined for gallium-67 citrate, indium-114m chloride, and iron-59 chloride cations complexed with tropolone in chloroform + water, octanol + water, olive oil + water, and olive oil + plasma two-phased systems. Tropolone proved to be highly effective in the lipid solubilization of these metal cations. Distribution studies in animals of these cations complexed with tropolone demonstrated an increased concentration of these cation complexes in tissues of high lipid content when compared with appropriate controls.

Animals↗

PubMed1995

Noninvasive assessment of no-reflow phenomenon in a canine model of reperfused infarction by contrast-enhanced magnetic resonance imaging.

The aim of this study was to test whether contrast-enhanced magnetic resonance (MR) imaging may assess in vivo the severity of the no-reflow phenomenon in a dog model of infarction with 2-hour coronary occlusion followed by reperfusion (6 hours). Subsecond MR imaging combined with intravenous bolus administration of superparamagnetic iron oxide particles (SPIO) was performed at the fifth hour of reperfusion. An MR index was calculated using the difference of signal-intensity enhancement between ischemic and nonischemic zones during the SPIO first pass. Dogs were separated into two groups according to the severity of ischemia: collateral blood flow in the central ischemic zone at 120 minutes of occlusion (radioactive microsphere technique) < 22.5% of the flow in the nonischemic zone (group I) or > 22.5% (group II). Mean collateral blood flow during occlusion was lower in group I (11.3% +/- 2.9%, n = 7) than in group II (66.8% +/- 19.8%, n = 6, p < 0.05). Mean infarct size was significantly larger in group I (58.6% +/- 4.9% of the area-at-risk, n = 7) than in group II (16.5% +/- 6.5%, n = 6, p < 0.05). For the entire population (n = 13), the infarct size was inversely correlated to the collateral blood flow (r = -0.64, p = 0.02, standard error of estimate = 0.24). The relative rate of enhancement in ischemic myocardium (MR index) was significantly lower in group I (38.1% +/- 10.9%) than in group II (142.8% +/- 32%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Uranium-contaminated soils: ultramicrotomy and electron beam analysis.

Uranium-contaminated soils from the U.S. Department of Energy (DOE) Fernald Site, Ohio, have been examined by a combination of backscattered electron imaging (BSE) and analytical electron microscopy with electron diffraction (AEM). The inhomogeneous distribution of particulate uranium phases in the soil required the development of a method for using ultramicrotomy to prepare transmission electron microscopy (TEM) thin sections from the SEM mounts. A water-miscible resin was selected that allowed comparison between SEM and TEM images, permitting representative sampling of the soil. Uranium was found in iron oxides, silicates (soddyite), phosphates (autunites), and uraninite (UO2 + x). No uranium was detected in association with phyllosilicates in the soil.

Electron Probe Microanalysis↗

PubMed1979

X-ray emission analysis of human plasma by proton excitation of thick samples in air.

Thick plasma samples have been irradiated in air by 2.3 MeV protons for trace elemental analysis by proton-induced X-ray emission spectroscopy. Accurate calibration curves were obtained for Fe, Zn and Sr and detection limits in dry plasma were estimated to be 0.08 PPM for Fe, 0.065 PPM for Zn and 0.12 PPM for Sr. Low temperature ashing of these samples improved the detection limits by a factor of 3 but reduced the precision and resulted in loss of bromine from the plasma. Mass absorption coefficients for low energy X-rays in dry plasma were measured and X-ray attenuation in the sample was found to prevent the detection of trace elements with Z less than 26. The method was used to determine Sr in plasma from a patient with bone disease, the Sr being a non-radioactive bone-seeking tracer element. The results, which were in the 3--13 PPM range, were in good general agreement with the analysis of the same samples by flame photometry.

Air↗

PubMed2002

Considerations on the use of radioisotopes in human nutrition research.

Tracer methodology using radioisotopes in human nutrition and metabolism research has been very productive but its use has been the object of unjustified limitations because of modeling decisions without adequate consideration of new data. These limitations have encumbered research studies in the metabolism of micro- and macronutrients particularly where nutritional deficiencies are prevalent. Even though stable isotope methodologies in human research are very useful in specific applications they are expensive and are often fraught with serious pitfalls, when compared to studies for the same purposes using radioisotopes. We have been developing safe radioisotopic methods to study the absorption and metabolism of micronutrients, especially iron and zinc, that can be applied to populations in the developing world. These and other applications of radioisotopes should allow scientists to conduct research diminishing the dependence on stable isotopes and on facilities and laboratories existing only in selected sites in the industrial world, and thus should enhance productive local and collaborative research. All radioisotopic research must be subjected to strict safety criteria, based on scientific evidence of risk, but should not be hampered by exaggerated fears of unfounded risk. Examples on the use of radio and stable isotopes to study iron and zinc absorptions are given including the radiation exposure and risk calculations.

Dose-Response Relationship, Radiation↗

PubMed1994

A model of galactic cosmic rays for use in calculating linear energy transfer spectra.

The galactic cosmic rays (GCR) contain fully stripped nuclei, from Hydrogen to beyond the Iron group, accelerated to high energies and are a major component of the background radiation encountered by satellites and interplanetary spacecraft. This paper presents a GCR model which is based upon our current understanding of the astrophysics of GCR transport through interstellar and interplanetary space. The model can be used to predict the energy spectra for all stable and long-lived radioactive species from H to Ni over an energy range from 50 to 50,000 MeV/nucleon as a function of a single parameter, the solar modulation level phi. The details of this model are summarized, phi is derived for the period 1974 to present, and results from this model during the 1990/1991 CRRES mission are presented.

Cosmic Radiation↗

PubMed1980

Transferrin-binding and iron-binding proteins of rabbit reticulocyte plasma membranes. Three distinct moieties.

1. Transferrin-membrane complexes and iron-binding membrane complexes were solubilized with sodium dodecyl sulfate from the plasma membranes of reticulocytes that had been incubated with (59Fe,125I)-labeled transferrin. Gel filtration of solubilized material demonstrated 125I-labeled transferrin complexed to two moieties, a minor component (Peak I) of apparent molecular weight 435,000 and a major component (Peak II) of apparent molecular weight 200,000. Most of the membrane 59Fe was located in Peak I. 2. Sepharose-bound anti-transferrin was used to purify the 125I-labeled transferrin-membrane complexes. The 59Fe/125I ratio in the transferrin complex purified from Peak I was the same as in the original transferrin and thus contained membrane-bound transferrin to which the 59Fe was still attached. The 59Fe/125I ratio in the purified Peak II transferrin complex was 0.33 times that of the original transferrin, indicating that more than 60% of its 59Fe had been delivered to the reticulocyte. 3. The purified transferrin complexes analyzed by SDS-polyacrylamide gel electrophoresis demonstrated a single band of apparent molecular weight 78,000 both by Coomassie blue stain for protein and by 125I radioactivity. The specific activity of this material was 0.27 and 0.56 times that of the original transferrin for Peak I and Peak II, respectively, indicating that transferrin in Peak I and II was bound to a membrane component with a molecular weight similar to that of transferrin. 4. The isoelectric focusing pattern of the Peak II transferrin complex showed isoelectric points of pH 6.7 and 6.2 compared to pH 5.4 for transferrin. 5. On the basis of these studies we propose that transferrin is first bound to a membrane protein and then delivers iron to a membrane component distinct and separate from the transferrin-binding moiety. Prior to its release, transferrin markedly depleted of iron is still bound to a component in the plasma membrane.

Animals↗

PubMed1989

Iron fortification of infant cereals: a proposal for the use of ferrous fumarate or ferrous succinate.

Hemoglobin-repletion tests in rats, organoleptic studies, and iron-absorption studies in humans were used to search for Fe sources with high bioavailability that could be added to infant cereals as alternatives to the Fe compounds currently used for fortification. From rat and organoleptic studies on 11 alternative Fe sources, ferrous fumarate, ferrous succinate, and ferric saccharate were selected as the most suitable for infant-cereal fortification and, by use of radioactive labels, absorption of those compounds from fortified cereal was measured in adult human volunteers. There was no difference in absorption between ferrous fumarate and ferrous sulfate whereas the values for ferrous succinate, ferrous saccharate (10% Fe), and ferric pyrophosphate were 92%, 74%, and 39% of the ferrous sulfate values, respectively. We conclude that ferrous fumarate and ferrous succinate are highly available Fe sources in man that can be used to fortify infant cereals without causing fat oxidation or discoloration.

Absorption↗

PubMed1977

Rhodanese-Mediated sulfur transfer to succinate dehydrogenase.

The interaction of the sulfurtransferase rhodanese (EC 2.8.1.1) with succinate dehydrogenase (EC 1.3.99.1), yeast alcohol dehydrogenase (EC 1.1.1.1) and bovine serum albumin was studied. Succinate dehydrogenase incorporates the sulfane sulfur of [35S]rhodanese and, in the presence of unlabelled rhodanese, also incorporates that of [35S]thiosulfate. Rhodanese releases most of its transferable sulfur and is re-loaded in the presence of thiosulfate. Rhodanese undergoes similar modifications with yeast alcohol dehydrogenase but this latter does not bind 35S in amounts comparable to those incorporated in succinate dehydrogenase: nearly all the 35S released by [35S]rhodanese is with low-molecular-weight compounds. Bovine serum albumin also binds very little sulfur and [35S]rhodanese present in the reaction mixture does not discharge its radioactive sulfur nor does it take up sulfur from thiosulfate. Sulfur release from rhodanese appears to depend on the presence of - SH groups in the acceptor protein. Sulfur incorporated into succinate dehydrogenase was analytically determined as sulfide. A comparison of the optical spectra of succinate dehydrogenase preparations incubated with or without rhodanese indicates that there is an effect of the sulfurtransferase on the iron-sulfur absorption of the flavorprotein. The interaction of rhodanese with succinate dehydrogenase greatly decreases the catalytic activity of rhodanese with respect to thiocyanate formation. This is attributed to modifications in rhodanese associated with the reduction of sulfane sulfur to sulfide. Thiosulfate in part protects from this deactivation. The reconstitutive capacity of succinate dehydrogenase increased in parallel with sulfur incorporated in that enzyme following its interaction with rhodanese.

Alcohol Oxidoreductases↗

PubMed2005

ABC transporter FtsABCD of Streptococcus pyogenes mediates uptake of ferric ferrichrome.

BACKGROUND: The Streptococcus pyogenes or Group A Streptococcus (GAS) genome encodes three ABC transporters, namely, FtsABCD, MtsABC, and HtsABC, which share homology with iron transporters. MtsABC and HtsABC are believed to take up ferric (Fe3+) and manganese ions and heme, respectively, while the specificity of FtsABCD is unknown. RESULTS: Recombinant FtsB, the lipoprotein component of FtsABCD, was found to bind Fe3+ ferrichrome in a 1:1 stoichiometry. To investigate whether FtsABCD transports Fe3+ ferrichrome, GAS isogenic strains defective in lipoprotein gene ftsB and permease gene ftsC were generated, and the effects of the mutations on uptake of Fe3+ ferrichrome were examined using radioactive 55Fe3+ ferrichrome. FtsB was produced in the wild-type strain but not in the ftsB mutant, confirming the ftsB inactivation. While wild-type GAS took up 3.6 x 10(4) Fe3+ ferrichrome molecules per bacterium per min at room temperature, the ftsB and ftsC mutants did not have a detectable rate of Fe3+ ferrichrome uptake. The inactivation of ftsB or ftsC also decreased 55Fe3+ ferrichrome uptake by >90% under growth conditions in the case of limited uptake time. Complementation of the ftsB mutant with a plasmid carrying the ftsB gene restored FtsB production and 55Fe3+ ferrichrome association at higher levels compared with the parent strain. The inactivation of mtsA and htsA and Fe-restricted conditions enhanced the production of FtsB and Fe3+ ferrichrome uptake. CONCLUSION: The FtsB protein bound Fe3+ ferrichrome, and inactivation of ftsB or ftsC, but not htsA or mtsA, diminished Fe3+ ferrichrome uptake, indicating that FtsABCD, but not HtsABC and MtsABC, is the transporter that takes up Fe3+ ferrichrome in GAS. Fe acquisition systems are virulence factors in many bacterial pathogens and are attractive vaccine candidates. The elucidation of the FtsABCD specificity advances the understanding of Fe acquisition processes in GAS and may help evaluating the GAS Fe acquisition systems as vaccine candidates.

ATP-Binding Cassette Transporters↗

PubMed2005

Large-scale modeling of reactive solute transport in fracture zones of granitic bedrocks.

Final disposal of high-level radioactive waste in deep repositories located in fractured granite formations is being considered by several countries. The assessment of the safety of such repositories requires using numerical models of groundwater flow, solute transport and chemical processes. These models are being developed from data and knowledge gained from in situ experiments such as the Redox Zone Experiment carried out at the underground laboratory of Aspö in Sweden. This experiment aimed at evaluating the effects of the construction of the access tunnel on the hydrogeological and hydrochemical conditions of a fracture zone intersected by the tunnel. Most chemical species showed dilution trends except for bicarbonate and sulphate which unexpectedly increased with time. Molinero and Samper [Molinero, J. and Samper, J. Groundwater flow and solute transport in fracture zones: an improved model for a large-scale field experiment at Aspö (Sweden). J. Hydraul. Res., 42, Extra Issue, 157-172] presented a two-dimensional water flow and solute transport finite element model which reproduced measured drawdowns and dilution curves of conservative species. Here we extend their model by using a reactive transport which accounts for aqueous complexation, acid-base, redox processes, dissolution-precipitation of calcite, quartz, hematite and pyrite, and cation exchange between Na+ and Ca2+. The model provides field-scale estimates of cation exchange capacity of the fracture zone and redox potential of groundwater recharge. It serves also to identify the mineral phases controlling the solubility of iron. In addition, the model is useful to test the relevance of several geochemical processes. Model results rule out calcite dissolution as the process causing the increase in bicarbonate concentration and reject the following possible sources of sulphate: (1) pyrite dissolution, (2) leaching of alkaline sulphate-rich waters from a nearby rock landfill and (3) dissolution of iron monosulphides contained in Baltic seafloor sediments. Based on these results, microbially mediated processes are postulated as the most likely hypothesis to explain the measured increase of dissolved bicarbonates and sulphates after tunnel construction.

Bicarbonates↗

PubMed2004

Trace elements in Jamaican tobacco.

The concentrations of 28 elements, in hand-made cigars, "rope" tobacco and freshly picked tobacco leaves from the parish of Manchester in central Jamaica, were compared with locally packaged and imported cigarettes and cigars. Except for chromium and vanadium, which are lower in the imported products, the elemental concentrations of all the brands sold in Jamaica are rather similar. The means for aluminium, cadmium, caesium, cerium, chromium, iron, thorium, uranium, vanadium and zinc for the Manchester material exceed the maximum values of the other tobaccos. The significant concentrations of heavy metals, and especially cadmium, which is about 50 times that of commercial cigarettes, reflect the known high concentrations in the soils in the region. This tobacco is not filtered and the smoke contains 50% of the cadmium. This, and the concentrations of radioactive elements, may indicate an additional health risk compared with commercial cigarettes. A study of three samples of marijuana indicates a similar level of risk from heavy metals.

Cannabis↗

PubMed1990

Ferritin determination in elderly people by enzyme immunoassay.

Iron is associated with important biological processes: Cellular and molecular oxidation, muscle contraction and infection resistance. Iron stores can be estimated by Ferritin (FTN) determination. FTN quantitation can be used in the early diagnosis of ferropenic anemia (precedes 3-6 months the clinical appearance of anemia) in pregnant women, children and elderly people. FTN serum levels are associated with high incidence diseases as malignant tumors and hepatopathies. Serum FTN concentration is in the range of ng/ml. So, high sensitivity techniques with radioactive, enzymatic, fluorescent or luminescent tracers are needed for FTN quantitation. An affinity antibody enzyme labelled procedure with a 2.5-500 ng/ml range, compatible with various plastic solid supports was developed to study Ferritinemia in elderly persons. Ferritinemia was found to be less than 20 ng/ml in 12% institutionalized elderly persons.

Aged↗

PubMed1982

Air pollution and lung cancer.

Epidemiological evidence proves conclusively that lung cancer correlates with air pollution. However, data on lung cancer death rates and smoking show that mankind accepts the risk of long-term and low-level exposure to carcinogens. As a rule, immediate benefits are sought and remote hazards ignored. Fear of atmospheric contamination by radioactive fallout seems to be the main factor for awareness of air pollution. Experimental works help us to understand physics of particle deposition in the lungs (inertial impactation, sedimentation, Brownian movement), shed light on carcinogenesis (eg, bay region theory in case of polycyclic aromatic hydrocarbons and surface charge changes regarding asbestos), show that atmospheric particulates accepted as harmless may act as co-carcinogens (eg, iron and benzo(a)pyrene) and stress the importance of in vitro researches (bacterial mutation tests, organ cultures, sister chromatid exchange system) to screen pollutants for their malignant potential and study their pathogenesis.

Aerosols↗

PubMed1988

Interaction of acidic isoferritins with human promyelocytic HL60 cells.

We have used undifferentiated human promyelocytic HL60 cells to study the binding of radioiodinated human ferritin in vitro. Specific binding of human heart ferritin could be demonstrated at 37 degrees C, whereas no binding of liver ferritin could be found. The uptake of labelled heart ferritin was abolished by incubation at 4 degrees C, by prior treatment of the HL60 cells with pronase and by the addition of human plasma to the medium. On the other hand, the addition of excess unlabelled human liver or rat liver ferritin had no effect on the uptake of labelled human heart ferritin. Dissociation studies showed that about 55% of the bound heart ferritin radioactivity could be released by incubation with medium alone and at least 90% with excess unlabelled heart ferritin. Over 70% of the dissociated ferritin could be precipitated with polyclonal anti-ferritin serum or trichloroacetic acid. More than two-thirds of the radioactivity which could not be released after washing in medium alone was recovered in the soluble intracellular fraction following cell lysis. Almost all of the soluble radioactivity could be precipitated with the polyclonal antiserum, indicating that very little lysosomal degradation of internalized heart ferritin had occurred. The present studies demonstrate a protein-mediated binding mechanism for acidic isoferritins on HL60 cells. These observations agree with published evidence that ferritin is often associated with cell membranes and are consistent with a possible role for the protein in the regulation of haematopoiesis or in iron transfer.

Cell Line↗