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Decreased bone uptake of technetium-99m polyphosphate in thalassemia major.

Bone scans were performed with Tc-99m stannous polyphosphate on four patients with thalassemia major. Three of the scans show generalized decrease in skeletal uptake of the radiopharmaceutical, associated with renal enlargement and markedly increased renal radioactivity. The skeletal findings are consistent with the known bone abnormalities in thalassemia major, which are secondary to the extensive marrow hyperplasia and include loss of trabeculae and cortical thinning with consequent loss of bone mass. The increased renal uptake is probably due in part to the increased renal excretion (secondary to the poor bone uptake) and in part to the tubular dilatation and renal enlargement associated with thalassemia major. In addition, the presence of excessive amounts of iron in these patients may play a role in both the skeletal and renal findings.

Adult↗

Sodium iron EDTA [NaFe(III)EDTA] as a food fortificant does not influence absorption and urinary excretion of manganese in healthy adults.

NaFe(III)EDTA is a promising iron (Fe) compound for food fortification programs because of its high Fe bioavailability from meals containing dietary inhibitors of Fe absorption such as phytic acid. However, this Fe compound is not currently used in any large-scale fortification program because of concern over its possible negative influence on the metabolism of other essential minerals or its possible influence on the absorption of potentially toxic elements, such as manganese (Mn). In this study, Mn absorption and urinary excretion were studied in adults after intake of an Fe-fortified weaning cereal labeled with 54Mn. In a crossover design, the fortification of the weaning cereal with Fe as NaFeEDTA was compared with ferrous sulfate. Manganese absorption was measured by extrapolation from whole-body retention data 10-30 d after intake, and urinary excretion of 54Mn was measured over 7 d. No significant differences in 54Mn absorption or urinary excretion were found; 1.1 +/- 0.15 and 0.91 +/- 0.35% of the ingested dose was absorbed from the cereal fortified with NaFe(III)EDTA and FeSO4, respectively. Urinary excretion of 54Mn was very low; the total radioactivity in urine represented 1.1 +/- 0.55% of the absorbed dose with NaFe(III)EDTA and 0.72 +/- 0.53% of the absorbed dose with FeSO4. Until now, Fe-fortification programs have met with only limited success. The introduction of NaFeEDTA as a food fortificant could be a useful tool to provide bioavailable Fe to vulnerable groups in the population and thus aid in combating Fe deficiency.

Absorption↗

Scintigraphic biodistribution and plasma kinetics of indium 111-labeled transferrin in dogs.

OBJECTIVE: To determine plasma clearance kinetics and imaging biodistribution of indium 111-labeled transferrin (111In-TF) in dogs. ANIMALS: 7 adult dogs. PROCEDURE: After 30 minutes' incubation of 18.5 MBq (0.5 mCi) of 111InCl3 with 1 ml of serum (n = 3) or 1 ml of plasma (n = 4) at 37 C, dogs were given autologous 111In-TF i.v., and serial blood samples and right lateral and dorsal scintigraphic images were obtained immediately and 1, 3, 5, 9, 22, and 48 hours later. Blood and plasma clearance kinetics were determined from a least-squares, nonlinear fit of the sample radioactivity data. Blood radioactivity was compared with plasma radioactivity to determine the extent of cellular labeling. Imaging biodistribution was characterized by subjective and objective assessment of blood pool, liver, gastrointestinal (abdomen) tract, kidney, and bone marrow activity. RESULTS: 111In-TF plasma clearance was best described by a biexponential fit, with early and late clearance half-times of 6 and 49 hours, respectively. The 111In was not redistributed between transferrin (plasma proteins) and blood cells. Imaging studies documented progressive liver and bone marrow uptake of the 111In-TF over 48 hours. Some radioactivity was evident in the colon of 1 dog on 48-hour images. Decay-corrected count rates (counts/pixel/mCi/kg/min) within the abdominal region of interest increased over the 48-hour imaging period and exceeded the blood pool (cardiac) activity at 20 hours after injection. CONCLUSION: 111In-TF has a biexponential plasma clearance in clinically normal dogs, with early and late clearance half-time of 6 and 49 hours, respectively. Scintigraphically, 111In-TF localizes to sites of iron storage (bone marrow and liver) over time. Some loss of 111In-TF via the gastrointestinal tract may be seen on late 48-hour images. CLINICAL RELEVANCE: 111In-TF appears to be a viable radiopharmaceutical for use in dogs, with specific application for identifying those with protein-losing enteropathy.

Animals↗

Collimation and surface counting in haematology.

The effect on the results obtained in surface counting investigations of using a dual detector counting system and multihole collimators has been investigated. The use of the additional detector results in smoother curves for the uptake of the radionuclide and the use of multihole collimators increases the discrimination of the counting system against the effects of radioactivity outside the region of interest. In a clinical trial to compare multihole collimation with conventional single hole collimation it was found that increased excess counts were obtained over the spleen with the multihole collimators in eight of ten cases.

Blood Cell Count↗

Effect of oxygen free radicals on corneal collagen.

Corneal collagen was labeled in vivo by injection of 14C-proline into the anterior chamber of rabbit eyes. The isolated corneal collagen was incubated in iron-free phosphate buffered saline (pH 7.4) containing 1 mM ascorbate and 0.1 mM CuSO4 for either 1 hour or 3 hours at 37 degrees. Addition of 2 volumes of 8M urea-1 mM dithiothreitol and heating for 1 min at 100 degrees solubilized virutually all of the collagen in the control incubations but left a significant amount of insoluble collagen in specimens exposed to the hydroxyl radical generating system. This residue amounted to 19% and 38% of the initial radioactivity in samples incubated for 1 h and 3 h, respectively. The chromatographic profiles (gel filtration on CL-4B) of the soluble fraction showed an increase in both aggregation and degradation products of collagen in the 1 h incubation mixture, whereas after 3 h there was an increase only in degradation products. These observations suggest that additional crosslinking of the soluble collagen aggregates observed at 1 h may be responsible for their subsequent disappearance at 3 h, with concomitant increase of the insoluble fraction. Collagen degradation by .OH may play a role in corneal ulceration, whereas hydroxyl radical-mediated crosslinking is consistent with age-dependent increases in insoluble collagen.

Animals↗

Use of biotin-labeled nucleic acids for protein purification and agarose-based chemiluminescent electromobility shift assays.

We have employed biotin-labeled RNA to serve two functions. In one, the biotin tethers the RNA to streptavidin-agarose beads, creating an affinity resin for protein purification. In the other, the biotin functions as a label for use in a modified chemiluminescent electromobility shift assay (EMSA), a technique used to detect the formation of protein-RNA complexes. The EMSA that we describe avoids the use not only of radioactivity but also of neurotoxic acrylamide by using agarose as the gel matrix in which the free nucleic acid is separated from protein-nucleic acid complexes. After separation of free from complexed RNA in agarose, the RNA is electroblotted to positively charged nylon. The biotin-labeled RNA is readily bound by a streptavidin-alkaline phosphatase conjugate, allowing for very sensitive chemiluminescent detection ( approximately 0.1-1.0 fmol limit). Using our system, we were able to purify both known iron-responsive proteins (IRPs) from rat liver and assess their binding affinity to RNA containing the iron-responsive element (IRE) using the same batch of biotinylated RNA. We show data indicating that agarose is especially useful for cases when large complexes are formed, although smaller complexes are even better resolved.

Animals↗

Natural radioactivity in the scale of water well pipes.

The natural radioactivity of 226Ra and 228Ra in scale samples taken from pipes used in several local water wells was investigated. The results showed 226Ra activities to be varying from 1284 to 3613 Bq/kg whereas, the 228Ra concentrations did not show any significant variation, all being low, below 30 Bq/kg. The 222Rn exhalations from these scale samples were also measured and compared with the 226Ra contents. The average ratio of 222Rn/226Ra was 31%. Chemical analyses showed that the main constituent of the scale samples was iron. The radiation dose rates from the pipes and scale were up to 100nSv/h. Although not a major hazard this could present a long-term risk if the scale materials were handled indiscriminately.

Environmental Monitoring↗

Reaction mechanisms in the geopolymeric conversion of inorganic waste to useful products.

High-performance materials for construction, waste immobilisation and an ever-growing range of niche applications are produced by the reaction sequence known as 'geopolymerisation'. In this process, an alkaline activating solution reacts with a solid aluminosilicate source, with solidification possible within minutes and very rapid early strength development. Geopolymers have been observed to display remarkable chemical and thermal stability, but due to their largely X-ray amorphous nature have only recently been accurately characterised. It has previously been shown that both fly ash and ground granulated blast furnace slag are highly effective as solid constituents of geopolymer reaction slurries, providing readily soluble alumina and silica that undergo a dissolution-reorientation-solidification process to form a geopolymeric material. Here a conceptual model for geopolymerisation is presented, allowing elucidation of the individual mechanistic steps involved in this complex and rapid process. The model is based on the reactions known to occur in the weathering of aluminosilicate minerals under alkaline conditions, which occur in a highly accelerated manner under the conditions required for geopolymerisation. Transformation of the waste materials to the mixture of gel and nanocrystalline/semicrystalline phases comprising the geopolymeric product is described. Presence of calcium in the solid waste materials affects the process of geopolymerisation by providing extra nucleation sites for precipitation of dissolved species, which may be used to tailor setting times and material properties if desired. Application of geopolymer technology in remediation of toxic or radioactive contaminants will depend on the ability to analyse and predict long-term durability and stability based on initial mix formulation. The model presented here provides a framework by which this will be made possible.

Aluminum Silicates↗

241Am migration in a sandy aquifer studied by long-term column experiments.

The migration behavior of 241Am(III) in a sandy aquifer was studied under near-natural conditions by long-term column experiments of more than 1 year duration. Columns with 50 cm length and 5 cm in diameter were packed with aeolian quartz sand and equilibrated with two different groundwaters having an original dissolved organic carbon concentration (DOC) of 1.1 and 7.2 mg x dm(-3), respectively,from the Gorleben site (Lower Saxony, Germany). In each experiment, 1 cm3 of Am-spiked groundwater ([Am] = 0.2 to 2 micromol x dm(-3)) was injected into the column. The flow rate of the groundwater was adjusted to 0.28 m x d(-1). A small colloid-borne Am fraction was found to elute together with tritiated water. After 414 and 559 days, respectively, the experiments were terminated. Whereas the nonsorbing tracer of tritiated water would have covered a distance of about 350 m in that time period, the maximum of the Am activity was detected between 32 and 40 mm column length. Applying selective dissolution analysis to the sand surface, Am was found to be preferentially bound to iron hydroxide/oxide sites. From this Am distribution, a retardation factor R of about 10(4) was determined and compared to static batch experiments. The Am breakthrough was calculated forthe conditions of the column experiment

Americium↗

Comparison of 99mTc complexes for renal imaging.

The distribution of 17 different agents for renal imaging was compared in the rabbit by organ radioassay at 1 hr. Similarly, 99mTc complexes of iron-ascorbate, glucoheptonate (GHA) and 2,3-dimercaptosuccinic acid (DMS), and 203Hg-chlormerodrin were compared in the dog. The distribution of 99mTc-GHA and DMS was assessed in the human by blood and urinary clearance, external renal measurements, and scintillation camera imaging, and compared with older renal radiopharmaceuticals. Radiation dose estimates, based chiefly on human data, were calculated. Technetium-99m-DMS reaches a high concentration in the renal cortex and its urinary excretion rate and blood clearance are slow. It is excellent for imaging the renal parenchyma without activity in pelvocalyceal collecting system. However, it readily oxidizes and must be used within 30 min of preparation. The biologic distribution of 99mTc-GHA is similar to gluconate and iron-ascorbate complex. Its renal concentration is not as great as that of DMS but its blood and urinary clearances are much faster, resulting in lower radiation doses to most organs. Early camera images with this agent usually demonstrate both the renal parenchyma and collecting system. In later images, ther is excellent demonstration of the parenchyma alone, superior to that obtained with 99mTc-Sn-DTPA. It is a very stable complex and may be used for at least 5 hr after preparation. All radioactive renal agents examined to date have a significant concentration in the liver, making an accurate quantitative comparison between the two kidneys difficult.

Albumins↗

Effect of lactose, copper and iron on manganese retention and tissue distribution in rats fed dextrose-casein diets.

The effect of iron, lactose and copper on manganese retention was studied in rats fed two diets. Thirty-six male albino rats (75 to 100 g) were allotted to six groups of six rats each. Three groups received a purified manganese-free dextrose-casein diet, and three groups received the same purified diet with 17% lactose added at the expense of dextrose. One group fed each of the above diets received either a manganese-free mineral mixture, the mineral mixture with 5 ppm supplemental Cu or the same mineral mixture with Fe removed. After 7 days on the diets, each rat was given, by gavage, 10 muCi of 54Mn activity as 54MnCl2 in a sodium acetate buffer. On the third day after dosing, the rats were sacrificed and samples of liver, kidneys, semitendinosus muscle, spleen and tibia were taken for stable and radioactive manganese analysis. Lactose added to the purified diet depressed 54Mn retention in all tissues studied. Lactose addition also decreased specific activities of the livers and kidneys but tended to increase stable manganese values. Copper apparently had little direct effect on 54Mn retention but tended to reduce the effect of lactose on 54Mn retention. Omission of Fe greatly increased 54Mn retention values in all tissues studied with or without added lactose. Fe omission also significantly increased the specific activities and stable Mn values of livers and the specific activity of kidneys. The results indicate that low dietary Fe may be a contributing factor to the increased manganese retention observed in this study and a previous study.

Animals↗

Effect of water purification on its radioactive content.

We have analyzed the dissolved activity of various radionuclides of natural origin (226Ra and (234,235,235)U) and artificial origins (90Sr and (239+240)Pu), together with other non-radioactive physico-chemical parameters (pH, conductivity, dry residue, [Ca2+], [Mg2+], [K+] and [Fe(2+,3+)], in both pre-potable and potable water from 17 treatment plants in Extremadura (Spain). We have established a series of criteria and complementary techniques to the traditional methods of purification, aimed at the quantitative elimination of the presence in solution of the mentioned radionuclides. We highlight: (a) the increment of the mineral content of the water in its treatment succeeds in eliminating 226Ra, until reaching values close to 70%; (b) the increment of the mineralization of the water by addition of chemical reagents, conducted within the pH values 7.1 and 7.8, succeeds in eliminating up to 90% of the total uranium in dissolution; (c) the elimination of 90Sr during the purification is poor, in general, reaching average levels of only 15% when the purification process is practiced within concrete ranges for potable water (pH > 7, conductivity > 150 microS/cm, dry residue > 150 mg/l, [Ca2+] > 10 mg/l and [Mg2+] > 1.2 mg/l), and finally, (d) the decrease of the solubility of the iron, as low as it can get during the purification process, together with an increase of the conductivity associated, in principle, to parallel increments of other variables not analyzed in this work, such as SO4(2-), CO3(2-), etc., the activity of dissolved (239+240)Pu decreases to 90%. The application of the traditional processes of water purification outside the ranges and criteria formulated can increase the presence in dissolution up to 400%, for some radionuclides, largely the consequence of its redissolution from the non-soluble fraction of the water.

Electric Conductivity↗

Mineralogical compositions of aquifer matrix as necessary initial conditions in reactive contaminant transport models.

Mineralogical compositions and their spatial distributions are important initial conditions for reactive transport modeling. However, popular Kd-based "reactive" transport models only require contaminant concentrations in the pore fluids as initial conditions, and minerals implicitly represent infinite sources and sinks in these models. That situation results in a general neglect of mineralogical characterization in site investigations. This study uses a coupled multi-component reactive mass transport model to predict the natural attenuation of a ground water plume at a uranium mill tailings site in western USA. Numerous ground water geochemistry data are available at this site, but mineralogical data are sketchy. Even given the well-defined pore fluid chemistry, variations of secondary mineral species and mineral abundances in the aquifer resulted in significantly different modeling outcomes. Results show that the amount of calcite in the aquifer determines the distances of plume migration. The possible presence of jurbanite, an aluminum sulfate phase, can store acidity temporarily but cause more severe contamination on a later date. The surfaces of iron oxyhydroxides can store significant amounts of sulfate and protons and serve as a second source for prolonged contamination. These simulations under field conditions illustrate that mineralogical compositions are an essential requirement for accurate prediction of contaminant fate and transport.

Minerals↗

Bioremediation of 60Co from simulated spent decontamination solutions.

Bioremediation of 60Co from simulated spent decontamination solutions by utilizing different biomass of (Neurospora crassa, Trichoderma viridae, Mucor recemosus, Rhizopus chinensis, Penicillium citrinum, Aspergillus niger and, Aspergillus flavus) fungi is reported. Various fungal species were screened to evaluate their potential for removing cobalt from very low concentrations (0.03-0.16 microM) in presence of a high background of iron (9.33 mM) and nickel (0.93 mM) complexed with EDTA (10.3 mM). The different fungal isolates employed in this study showed a pickup of cobalt in the range 8-500 ng/g of dry biomass. The [Fe]/[Co] and [Ni]/[Co] ratios in the solutions before and after exposure to the fungi were also determined. At micromolar level the cobalt pickup by many fungi especially the mutants of N. crassa is seen to be proportional to the initial cobalt concentration taken in the solution. However, R. chinensis exhibits a low but iron concentration dependent cobalt pickup. Prior saturating the fungi with excess of iron during their growth showed the presence of selective cobalt pickup sites. The existence of cobalt specific sorption sites is shown by a model experiment with R. chinensis wherein at a constant cobalt concentration (0.034 microM) and varying iron concentrations so as to yield [Fe/Co]initial ratios in solution of 10, 100, 1000 and 287000 have all yielded a definite Co pickup capacity in the range 8-47 ng/g. The presence of Cr(III)EDTA (3 mM) in solution along with complexed Fe and Ni has not influenced the cobalt removal. The significant feature of this study is that even when cobalt is present in trace level (sub-micromolar) in a matrix of high concentration (millimolar levels) of iron, nickel and chromium, a situation typically encountered in spent decontamination solutions arising from stainless steel based primary systems of nuclear reactors, a number of fungi studied in this work showed a good sensitivity for cobalt pickup.

Biodegradation, Environmental↗

Mutant strains of Rhodopseudomonas spheroides lacking delta-aminolevulinate synthase: growth, heme, and bacteriochlorophyll synthesis.

Two mutant strains of Rhodopseudomonas spheroides were described which lacked delta-aminolevulinate synthase activity. They required delta-aminolevulinate for growth; they did not respond to protoporphyrin or magnesium photoporphyrin, and only poorly to hemin. Synthesis of cytochromes and heme by mutant H-4 was dependent upon delta-aminolevulinate; this strain did not form bacteriochlorophyll either with or without delta-aminolevulinate and, consequently, grew only under aerobic conditions. Mutant H-5 formed bacteriochlorophyll in response to delta-aminolevulinate and grew both anaerobically in the light and aerobically in the dark; the amount of delta-aminolevulinate needed for optimal anaerobic growth was higher than that required aerobically. Synthesis of bacteriochlorophyll and heme by suspensions of mutant H-5 incubated anaerobically in the light was dependent upon delta-aminolevulinate; bacteriochlorophyll production was completely inhibited by high aeration and by puromycin. The mutants differed in their ability to take up radioactive delta-aminolevulinate from the external environment; mutant H-5 was less active than mutant H-4 or the wild type. It was suggested that R. spheroides made only one form of delta-aminolevulinate synthase, which provided delta-aminolevulinate for bacteriochlorophyll and heme synthesis.

Acyltransferases↗

Erythrocyte antioxidant activity, serum ceruloplasmin, and trace element levels in subjects with alcoholic liver disease.

Erythrocyte antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and reduced glutathione, serum ceruloplasmin, and serum trace elements (copper, zinc, iron, and selenium) related to antioxidant enzymes were assayed in subjects with alcoholic liver disease of different degrees of severity. The erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis had an unbalanced antioxidant system (normal superoxide dismutase, low catalase and glutathione peroxidase activities, and low glutathione content). Serum ceruloplasmin levels were in the normal range. Levels of the serum trace elements zinc and selenium were significantly low in subjects with moderate and severe cirrhosis, whose red cell half-life was also significantly short, as measured by radioactive chromium. These data suggest that the erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis are less protected against oxidant stress. The particular erythrocyte antioxidant system and serum trace element pattern may play a role in the genesis of hemolytic disorders and of alcoholic hepatic damage.

Adult↗

Metabolism of hepatic haem and 'green pigments' in rats given 2-allyl-2-isopropylacetamide and ferric citrate. A new model for hepatic haem turnover.

We have studied effects of single doses of 2-allyl-2-isopropylacetamide and ferric citrate on hepatic haem turnover in rats. Haem was pre-labelled by intraperitoneal administration of 5-amino-[4-(14)C]laevulinate 4h before other treatments. Computer-assisted analysis of the haem decay curve showed that at least two exponential components were involved implying two haem pools. In control rats the size of the rapidly-turning-over pool was 38% of the total. Treatment with 2-allyl-2-isopropylacetamide alone resulted in a 2.3-fold increase in the fractional size of this pool. Treatment with ferric citrate alone increased the size of this pool 1.8-fold; treatment with both agents together had no measurable effect beyond that produced by 2-allyl-2-isopropylacetamide. The apparent rate constant for disappearance of labelled haem from the first pool was not affected by treatment with 2-allyl-2-isopropylacetamide or ferric citrate, indicating that these treatments affect hepatic haem turnover primarily by altering the distribution of haem synthesized in the liver. The increased haem degradation after treatment with 2-allyl-2-isopropylacetamide alone was associated with the accumulation of ;green pigments' in the liver. These pigments were detectable 1.5h after drug treatment; their total amount increased steadily for 28h and then declined. Despite this increase in amount, radioactivity of the ;green pigment' fraction fell rapidly in a biphasic fashion. Some of the radioactivity that initially was found in the ;green pigment' fraction was later found in an aqueous fraction, not extractable by acidic ethyl acetate. Rats given ferric citrate together with 2-allyl-2-isopropylacetamide accumulated less ;green pigments'.

Acetamides↗

Improved methods for genotype determination of human alcohol dehydrogenase (ADH) at ADH 2 and ADH 3 loci by using polymerase chain reaction-directed mutagenesis.

The human gene for producing alcohol dehydrogenase (ADH; EC 1.1.1.1) is polymorphic at ADH 2 and ADH 3 loci. Until now, the study of this polymorphism required liver biopsy or allele-specific radioactive probes. We have used directed mutagenesis by the polymerase chain reaction (PCR) to amplify and analyze the genotype of ADH 2 and ADH 3 loci. Thus, we could determine easily and unambiguously the complete genotype at these two loci by using a microsample of blood and restriction fragment length polymorphism after DNA amplification by PCR.

Alcohol Dehydrogenase↗