The use of radioactive isotopes in the investigation of blood disorders.
Explore the source record for details and available documents.
Anemia, Hemolytic↗
SEARCH · PubMed Health
Results for “IRON, RADIOACTIVE”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Liposome-encapsulated desferrioxamine in experimental iron overload.
We have encapsulated desferrioxamine (DF) in multilamellar liposomes (ML) and unilamellar liposomes (UL). Liposomes were prepared either with or without a glycolipid, i..e. galactocerebroside (GC). The average diameter of ML was 0.5 microgram, and that of UL was 0.08 microgram. Less tha 5% of DF leaked out from the liposomes after incubation in mouse plasma for 6 h. 59Fe-ferritin and 59Fe-labelled heat damaged erythrocytes (59Fe-DRBC) were administered to normal and hypertransfused mice as models of iron overload. Ferritin was used to label liver parenchymal cells and DRBC to label the Kupffer cells of the liver. A single injection of ML or UL with or without galactocerebroside into normal and hypertransfused mice enhanced from 3- to 15-fold the urinary excretion of radioiron from 59Fe-ferritin and from 59Fe-DRBC injected mice. For both the normal and hypertransfused mice, liposomes containing GC removed more 59Fe radioactivity from mice receiving 59Fe-DRBC. Thus GAC-liposomes may have a higher affinity for parenchymal cells of the liver, whereas liposomes without the glycolipid may have a higher uptake by the Kupffer cells.
Animals↗
Effects of iron deficiency anemia on delayed cutaneous hypersensitivity in mice.
In the present study, the effect of iron-deficiency anemia on delayed cutaneous hypersensitivity was measured using weanling C57BL/6 female mice which were fed either an ad libitum control diet supplemented with 25 to 30 mg Fe/kg diet (FePO4), an iron-deficient test diet (5 to 6 mg Fe/kg diet), or pairfed control diet (25 to 30 mg Fe/kg diet). When skin sensitizing agent (dinitrofluorobenzene) was applied to these animals and skin responses were measured 3 to 5 days later, anemic mice showed a significantly decreased inflammatory skin response than either control or pairfed mice. Five days after sensitization, the animals were challenged with dinitrofluorobenzene painted on the right ear and an equal dose of only the solvent on the left ear followed by 125I-deoxyuridine injected intraperitoneally. The ratio of either total or DNA associated radioactivity incorporated into the right over the left ears was significantly lower in anemic mice than either control or pairfed mice. A single dose of Imferon injected 24 h before the recall dose of dinitrofluorobenzene restored the ratio of 125I-dUR incorporated in anemic mice without having any significant effect on either the control or pairfed groups. The results suggest that iron is not required for sensitization but is required for an effective inflammatory response.
Anemia, Hypochromic↗
Escherichia coli formate-hydrogen lyase. Purification and properties of the selenium-dependent formate dehydrogenase component.
The formate-hydrogen lyase complex of Escherichia coli decomposes formic acid to hydrogen and carbon dioxide under anaerobic conditions in the absence of exogenous electron acceptors. The complex consists of two separable enzymatic activities: a formate dehydrogenase and a hydrogenase. The formate dehydrogenase component (FDHH) of the formate-hydrogen lyase complex was purified to near homogeneity in two column chromatographic steps. The purified enzyme was composed of a single polypeptide of molecular weight 80,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Metal analysis showed each mole of enzyme contained 3.3 g atoms of iron. Denaturation of FDHH released a compound which, when oxidized, displayed a fluorescence spectrum similar to that of the molybdopterin cofactor found in certain other enzymes. The enzyme contained selenium in the form of selenocysteine as determined by radioactive labeling of the enzyme with 75Se and amino acid analysis. FDHH activity was maximal between pH 7.5 and 8.5; however, the enzyme was maximally stable at pH 5.3-6.4 and highly unstable above pH 7.5. Nitrate and nitrite salts caused a drastic reduction in activity. Although azide inhibited FDHH activity, it also protected the enzyme from inactivation by oxygen.
Amino Acid Sequence↗
[Detection of special radionuclides in waste water from nuclear power plants].
For the nuclear power stations in the Federal Republic of Germany, the emissions of the radionuclides C 14, P 32, Fe 55 and Ni 63 in liquid effluents were investigated for several years. For the seven nuclear power stations, for which C 14 was measured for years, the releases in liquid effluents were in the range of 1 to 67 mCi. Yearly releases of P 32 generally do not exceed 0,5 mCi. Exceptions are boiling water reactors during the first two or three years after starting operation. Yearly releases up to 30 mCi were measured. The releases of Fe 55 and Ni 63 are in the range of 1 to 20 mCi per year and thus, in general, low compared to the releases of other activated corrosion products. As a consequence of decontamination measures especially during long shut down of a facility, yearly releases up to 68 mCi of Fe 55 and 190 mCi of Ni 63 occurred. The hypothetical radiation exposure of the public, resulting from these releases is low. The dose is below 1 mrem/a.
Carbon Radioisotopes↗
[Experience in the clinical use of radioactive indicators for the quantitative assessment of erythropoiesis in chronic lympholeukosis].
Explore the source record for details and available documents.
Anemia↗
Structural evidence for an anion-directing track in the hen ovotransferrin N-lobe: implications for transferrin synergistic anion binding.
The transferrins are a class of iron-binding proteins that require the presence of a synergistic anion for conformation-dependent binding of ferric ions. Bromopyruvate, a known synergistic anion and affinity label of ovotransferrin (oTF) [Bailey, C. T., Patch, M. G., & Carrano, C. J. (1988) Biochemistry 27, 6276-6282], was used to probe the structure of the metal- and anion-binding sites of the functional N- and C-terminal proteolytic halves (oTF/2N and oTF/2C, respectively) of ovotransferrin. Incubation of oTF/2N with [2-14C]bromopyruvate in the presence of Fe3+ ions resulted in the incorporation of 0.70 mol of 14C label/mol of oTF/2N; 14C-labeled oTF/2N was then purified and digested sequentially with trypsin and V8 protease to determine the sites of modification. Quantification of 14C radioactivity, analysis of purified 14C-labeled peptides by gas-phase sequencing and mass spectrometry demonstrated that chemical modification was restricted to nucleophilic residues contained in a fragment corresponding to residues 189-204 of oTF/2N, including Lys 199, Lys 202, and His 196. Lysine 199 was also protected from modification with [3H]CH2O in iron-saturated oTF/2N, suggesting the involvement of this residue in anion binding by the apo conformation [Anderson, B. F., Baker, H. M., Norris, G. E., Rumball, S. V., & Baker, E. N. (1990) Nature 344, 784-787]. Lysine 199 is conserved as a basic residue in the N-terminal metal-binding domains of the transferrins but not in the homologous C-terminal metal-binding domains. Identical trials with oTF/2C showed binding, but not modification, with bromopyruvate. These data suggest that Lys 199, Lys 202 and His 196, which are located on an alpha-helix (8) that terminates at the anion-binding site [Dewan, J. C., Mikame, B. Hirose, M., & Sacchettini (1993) Biochemistry 32, 11963-11968], attract and channel the synergistic anion to the anion-binding site. The presence or absence of basic residues in the metal-binding lobes of transferrins may account for the different anion- and metal-binding characteristics observed for the iron-binding sites of these proteins.
Amino Acid Sequence↗
Tomato metabolism and porphyrin-catalyzed oxidation of pyriproxyfen.
Investigation of the metabolism of [(14)C]pyriproxyfen [4-phenoxyphenyl (R,S)-2-(2-pyridyloxy)propyl ether] in tomato fruits (Lycopersicon esculentum Mill. cv. Ponterosa) was conducted by topical application of acetonitrile solution or emulsifiable concentration formulation three times at 35, 21, and 7 days before harvest. Most of the radioactivity remained on the fruit surface or in the plant tissues as intact pyriproxyfen with minor metabolites formed via hydroxylation at the 4'-position of the phenoxy ring or cleavage of ether linkages. The biomimic chemical oxidation model using iron porphyrin as a catalyst and hydrogen peroxide was found to well reproduce the primary metabolites detected in the metabolism study. The electrophilic reaction indices obtained by AM1 molecular orbital calculations supposing involvement of cytochrome P-450 were successfully applied to evaluate the potentially higher reactive sites in pyriproxyfen.
Acetonitriles↗
Development of studies of TPO gene and its application in nuclear medicine.
Thyroperoxidase (TPO) is a glycosylated protein bound to the apical plasma membrane of thyrocytes. It is the key enzyme in the synthesis of thyroid hormones. Its gene structure and transcriptional regulation have been studied in detail. This article reviews the structure, function and transcriptional regulation of the TPO gene, and the relationship between TPO, thyroid diseases and radioactive iodide therapy.
Amino Acid Sequence↗
Identification of a 29 kDa protein in the envelope of Mycobacterium smegmatis as a putative ferri-exochelin receptor.
Evidence of a direct association between ferri-exochelin, the major extracellular siderophore of Mycobacterium smegmatis, and a 29 kDa protein has been obtained by three separate methods. (1) Direct binding of 55Fe(III)-exochelin by the 29 kDa protein in an envelope preparation from iron-deficient cells was demonstrated by the extraction of a complex with the non-denaturing detergent CHAPS, and subsequent CHAPS-PAGE and autoradiography. (2) Affinity chromatography on a chemically synthesized ferri-exochelin-Sepharose 4B matrix led to the retention of the 29 kDa protein and a 25 kDa protein. The smaller protein was partially eluted with 1 mM ferri-exochelin although it did not form a stable complex with ferri-exochelin. The 29 kDa protein could not be eluted from the affinity matrix with 1 mM ferri-exochelin either alone or with 1 M NaCl. Only 2% (w/v) SDS could do this, but resulted in protein denaturation. (3) Incubation of 55Fe-exochelin with CHAPS-solubilized envelope proteins in free solution followed by ion-exchange chromatography resolved three radioactive peaks; subsequent analysis by SDS-PAGE showed that the peak with the highest 55Fe-binding activity per unit protein contained both the 29 and 25 kDa proteins. A direct association was demonstrated between the 29 kDa protein and 55Fe-exochelin by gel filtration. The evidence suggests that the 29 kDa iron-regulated envelope protein of M. smegmatis is a ferri-exochelin-binding protein and that the 25 kDa protein, which corresponds in size to a previously reported iron-regulated envelope protein in this bacterium, may have a role in the formation or maintenance of this complex. Proteins extracted from the cell envelope of iron-deficient M. smegmatis with CHAPS were dialysed to remove the detergent, incorporated into liposome suspensions and then incubated with 55Fe(III)-exochelin. This increased the retention of 55Fe by 133-fold compared to proteins not placed in liposomes. Retention of 55Fe was dependent upon the protein loading of the liposomes. Gel filtration confirmed that the iron was retained by these vesicles and even after dialysis the majority of 55Fe was still retained by the vesicles. Re-solubilization of the labelled proteo-liposomes in various detergents gave limited recovery of a ferri-exochelin-protein complex. Attempts to resolve this complex by Triton X-100 PAGE led to separation of the two entities. The complex was stable, however, in a CHAPS-PAGE system.
Cholic Acids↗
SufS is a NifS-like protein, and SufD is necessary for stability of the [2Fe-2S] FhuF protein in Escherichia coli.
Escherichia coli fhuF mutants, a sufS::MudI mutant, and a sufD::MudI mutant were found to have the same phenotype: the inability to use ferrioxamine B as an iron source in a plate assay. In addition, the sufS and sufD genes were shown to be regulated by the iron-dependent Fur repressor. Sequence analysis revealed that the sufS open reading frame corresponds to orf f406. The protein SufS belongs to the family of NifS-like proteins, which supply sulfur for [Fe-S] centers. The protein FhuF contains a [2Fe-2S] center. A mutation in the upstream sufD gene (orf f423) caused the same phenotype. The T7 expression system and a His tag allow the isolation in good yield of the FhuF protein from a wild-type strain. In contrast, overproduction of the protein in a DeltasufD strain failed. Radioactive labeling of N-His-FhuF with [35S]methionine showed that the protein was unstable in the DeltasufD mutant.
Amino Acid Sequence↗
Use of the mean transit time of an intravascular contrast agent as an exchange-insensitive index of myocardial perfusion.
A simple two-compartment model was used to study the effects of water exchange on the signal produced by an inversion recovery prepared rapid gradient-echo sequence during the first passage of a low dose of an intravascular contrast agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the vascular and extravascular spaces caused the form of the signal changes during the first pass to be dependent on both the fractional sizes of the vascular and extravascular compartments and on the exchange rate. Unless the effects of exchange are minimized by using a very short inversion time, parameters such as the peak height and area under the curve will be affected by regional and/or pathological variations in the exchange rate and the size of the vascular fraction. The mean transit time (MTT) is, however, less affected by water exchange. Experimental first-pass data produced by intravascular low-dose injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as derived from the first-pass curves, without deconvolution with the arterial input function, was well correlated with the myocardial blood flow (MBF) as measured using radioactive microspheres (r = 0.70, n = 52, P < 0.01). Other first-pass parameters such as the peak height or area under the curve exhibited either a poorer, or no, correlation with the MBF. The data suggest that the MTT of the first pass of an intravascular contrast agent may be a robust, quantitative method for assessing myocardial blood flow in patients.
Animals↗
Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia.
The present study provides evidence for anterograde axonal transport of manganese (Mn) in the basal ganglia. Microinjections of 54Mn into rat substantia nigra or striatum revealed region-specific accumulation and retention of the isotope in globus pallidus, striatum, thalamus and substantia nigra for up to at least 48 or 72 h respectively. Within 4 h after intrastriatal injection of 54Mn, radioactivity accumulated in the substantia nigra, suggesting axonal transport of the metal. Subsequent studies using bilateral 54Mn injections into striatum or substantia nigra and unilateral colchicine injections into or transection of the medial forebrain bundle confirmed axonal transport of Mn through these fibres. Selective destruction of the striatonigral or nigrostriatal pathways using quinolinic acid or 6-hydroxydopamine 2 weeks before injection of the isotope, revealed uptake of 54Mn by cell bodies of both gamma-aminobutyric acidergic striatal and dopaminergic nigral neurons and subsequent anterograde transport through striatonigral or nigrostriatal fibres. In addition, the quinolinic acid-lesioned striatum retained three times more radioactivity than the intact striatum. In conclusion, the present data suggest that both glial cells and striatonigral and nigrostriatal neurons are potential targets for Mn toxicity. These results and the selective neurotoxicity of Mn are discussed with respect to the iron transport protein transferrin, transferrin receptors, the iron storage protein ferritin, and mitochondrial dysfunction.
Animals↗
Radioactive sputter cathodes for 32P plasma-based ion implantation.
The development of clinical treatments involving the use of beta-emitting millimetric and sub-millimetric devices has been a continuing trend in nuclear medicine. Implanted a few nanometers below the surface of endovascular implants, seeds or beads, beta-emitting radioisotopes can be used in a variety of biomedical applications. Recently, new technologies have emerged to enable the rapid and efficient activation of such devices. A pulsed, coaxial electron cyclotron resonance plasma reactor was designed and tested to demonstrate the feasibility of plasma-based radioactive ion implantation (PBRII). It has been shown that such plasma reactors allow for the implantation of radioisotopes (32P) into biomedical devices with higher efficiencies than those obtained with conventional ion beams. Fragments containing radioactive atoms are produced in the implanter by means of a negatively biased solid sputter cathode that is inserted into an argon plasma. Dilute orthophosphoric acid solutions (H3(32)PO4) are used for the fabrication of flat sputter targets, since they offer a high radioisotope content. However, the aggregation of the radioactive solute into highly hygroscopic ring-like deposits rather than flat, thin radioactive films is observed on certain substrates. This article describes the effect of this nonuniform distribution of the radioisotopes on the efficiency of PBRII, and presents a technique which enables a better distribution of 32P by coating the substrates with iron. The iron coating is shown to enable optimal radioisotope sputtering rates, which are essential in 32P-PBRII for the efficient activation of millimetric biomedical devices such as stents or coils.
Gold↗
Haem synthesis from exogenous 5-aminolaevulinate in cultured chick-embryo hepatocytes. Effects of inducers of cytochromes P-450.
The effects of inducers of cytochrome P-450 on haem biosynthesis from 5-aminolaevulinate were examined by using cultured chick-embryo hepatocytes. Cultures treated with either 2-propyl-2-isopropylacetamide or 3-methylcholanthrene contained increased amounts of cytochrome P-450 and haem. After treatment for 3 h with 5-amino[4-14C]laevulinate, the relative amounts of radioactivity accumulating as haem corresponded to the relative amounts of total cellular haem, but not to increases in the amounts of cytochrome P-450. Treatment with 5-aminolaevulinate did not alter cellular haem or cytochrome P-450 concentrations in either control or drug-treated cultures. The mechanism of the enhanced accumulation of radioactivity in haem was investigated. Although 2-propyl-2-isopropylacetamide enhanced the uptake of 5-aminolaevulinate and increased the cellular concentration of porphobilinogen 1.5-fold, these changes did not account for the increases in haem radioactivity. The inducing drugs had no effect on the rates of degradation of radioactive haem, but appeared to enhance conversion of protoporphyrin into haem. This latter effect was shown by: (1) a decreased accumulation of protoporphyrin from 5-aminolaevulinate in cells treated with inducers, and (2) complete prevention of this decrease if the iron chelator desferrioxamine was present. We conclude that inducers of cytochrome P-450 may increase haem synthesis not only by increasing activity of 5-aminolaevulinate synthase, but also by increasing conversion of protoporphyrin into haem.
Allylisopropylacetamide↗
Sorption of uranium(VI) onto ferric oxides in sulfate-rich acid waters.
The mechanisms of the uranium(VI) sorption on schwertmannite and goethite in acid sulfate-rich solutions were studied by Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy. The samples were prepared under N2 atmosphere and initial uranium(VI) concentrations of 1 x 10(-5) (pH 6.5) to 5 x 10(-5) M (pH 4.2). The ionic strength was adjusted using 0.01 M Na2SO4 or 0.01 M NaClO4, respectively. The EXAFS structural parameters for uranium(VI) sorbed on goethite in sulfate-rich, acid and near-neutral solutions indicate that uranium(VI) forms an inner-sphere, mononuclear, bidentate surface complex. This complex is characterized by a uranium-ferric-iron distance of approximately 3.45 A. Uranium(VI) sorbed onto schwertmannite in acid and sulfate-rich solution is coordinated to one or two sulfate molecules with a uranium-sulfur distance of 3.67 A. The EXAFS results indicate formation of binuclear, bidentate surface complexes and partly of mononuclear, monodentate surface complexes coordinated to the structural sulfate of schwertmannite. The formation of ternary uranium(VI)-sulfate surface complexes could not be excluded because of the uncertainty in assigning the sulfate either to the bulk structure or to adsorption reactions. The uranium(VI) adsorption onto schwertmannite in perchlorate solution occurs predominantly as a mononuclear, bidentate complexation with ferric iron due to the release of sulfate from the substrate.
Adsorption↗
Phenolic ethylenediamine derivatives: a study of orally effective iron chelators.
Of 35 potential iron chelators screened for in vivo activity in rats, a group of phenolic compounds with excellent chelating properties were identified. These included N,N'-ethylene-bis(o-hydroxyphenylglycine) (EHPG), N,N'-Bis(o-hydroxybenzyl)-ethylenediamine diacetic acid (HBED), and their respective dimethyl esters (dmEHPG and dmHBED). All four phenolic compounds produced a marked increase in the fecal excretion of hepatocellular radioiron. This amounted to 42% of total body radioactivity with dmEHPG, 58% with EHPG, 63% with HBED, and 80% with dmHBED after a single injection of 40 mg/animal. At a dose of 5 mg/animal, EHPG, HBED, and dmHBED were 9, 12, and 15 times more potent, respectively, than deferoxamine. Both dimethyl esters showed significant oral activity; oral dmEHPG retained 1/3 and dmHBED retained 2/3 of the effect of the same dose given by intramuscular injection. The ester dmHBED combines oral effectiveness with superior chelating ability, selective hepatocellular action, and low apparent toxicity. It may represent a significant advance in the development of new iron chelating drugs.
Administration, Oral↗
Pharmacokinetics of 1-nitrosomelatonin and detection by EPR using iron dithiocarbamate complex in mice.
The N-nitroso-derivative of melatonin, NOM (1-nitrosomelatonin), which has been demonstrated to be a NO* [oxidonitrogen*] donor in buffered solutions, is a new potential drug particularly in neurological diseases. The advantage of NOM, a very lipophilic drug, is its ability to release both melatonin and NO*, an easily diffusible free radical. In order to evaluate the distribution and the pharmacokinetics of NOM, [O-methyl-3H]NOM was administered to and followed in mice. A complementary method for monitoring NOM, EPR, was performed in vitro and ex vivo with (MGD)2-Fe2+ (iron-N-methyl-D-glucamine dithiocarbamate) complex as a spin trap. The behaviour of NOM was compared with that of GSNO (S-nitrosoglutathione), a hydrophilic NO* donor. In the first minutes following [O-methyl-3H]NOM intraperitoneal injection, the radioactivity was found in organs (6% in the liver, 1% in the kidney and 0.6% in the brain), but not in the blood. In both liver and brain, the radioactivity content decreased over time with similar kinetics reflecting the diffusion and metabolism of NOM and of its metabolites. Based on the characterization and the quantification of the EPR signal in vitro with NOM or GSNO using (MGD)2-Fe2+ complex in phosphate-buffered solutions, the detection of these nitroso compounds was realized ex vivo in mouse tissue extracts. (MGD)2-Fe2+-NO was observed in the brain of NOM-treated mice in the first 10 min following injection, revealing that NOM was able to cross the blood-brain barrier, while GSNO was not.
Animals↗