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PubMed1990

12-[(5-iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoic acid: biological recognition by cholesterol esterase and acyl-CoA:cholesterol O-acyltransferase.

Potential probes of protein cholesterol and fatty acid binding sites, namely, 12-[(5-iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoate (IFA) and its coenzyme A (IFA:CoA) and cholesteryl (IFA:CEA) esters, were synthesized. These radioactive, photoreactive lipid analogues were recognized as substrates and inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol esterase, neutral lipid binding enzymes which are key elements in the regulation of cellular cholesterol metabolism. In the dark, IFA reversibly inhibited cholesteryl [14C]oleate hydrolysis by purified bovine pancreatic cholesterol esterase with an apparent Ki of 150 microM. Cholesterol esterase inhibition by IFA became irreversible after photolysis with UV light and oleic acid (1 mM) provided 50% protection against inactivation. Incubation of homogeneous bovine pancreatic cholesterol esterase with IFA:CEA resulted in its hydrolysis to IFA and cholesterol, indicating recognition of IFA:CEA as a substrate by cholesterol esterase. The coenzyme A ester, IFA:CoA, was a reversible inhibitor of microsomal ACAT activity under dark conditions (apparent Ki = 20 microM), and photolysis resulted in irreversible inhibition of enzyme activity with 87% efficiency. IFA:CoA was also recognized as a substrate by both liver and aortic microsomal ACATs, with resultant synthesis of 125IFA:CEA. IFA and its derivatives, IFA:CEA and IFA:CoA, are thus inhibitors and substrates for cholesterol esterase and ACAT. Biological recognition of these photoaffinity lipid analogues will facilitate the identification and structural analysis of hitherto uncharacterized protein lipid binding sites.

Acyl Coenzyme A↗
PubMed1996

Uranium skeletal dosimetry and distribution in young adult beagles: a guide for calculating uranium skeletal doses in humans.

Uranium isotopes were given via single intravenous injection into 22 young adult beagle dogs of both sexes to determine the metabolism of this element. Animals were given either 232U, 233U, 238U, or a combination of 232 (+) 233U. Calculations to assign a value of skeletal dose for each dog were performed using published radioactive properties of each uranium isotope and the metabolic data (including measured retention and skeletal distribution) derived from this study during a period of up to 2 y after injection. We believe that the procedures illustrated in this communication can serve as a useful pattern for estimating skeletal radiation doses to humans contaminated with 232U, 233U, or 238U.

Animals↗
PubMed2005

Evaluation of novel whole-body high-resolution rodent SPECT (Linoview) based on direct acquisition of linogram projections.

UNLABELLED: Studies of the biodistribution of radiolabeled compounds in rodents frequently are performed during the process of development of new pharmaceutical drugs. This article presents the evaluation of a new whole-body animal SPECT system, called the Linoview SPECT system. METHODS: Linoview SPECT is based on the linear orbit acquisition technique associated with slit-aperture collimators mounted on 4 pixelated CsI(Na) detectors composed of an array of small, individual crystal elements. Sliding iridium rods allow variation of the collimator aperture. Hot-rod and cold-rod phantoms filled with (99m)Tc were imaged. Mice were imaged, and kidney radioactivity was measured after injection of (99m)Tc-dimercaptosuccinic acid and (111)In-diethylenetriaminepentaacetic acid-d-Phe(1)-octreotide ((111)In-pentetreotide; Octreo-Scan(111)). RESULTS: Phantom studies showed that hot rods separated by 0.35 mm can be distinguished and that 0.65-mm-diameter cold rods can be visualized, both at low-counting-rate acquisitions (111 and 59 MBq x h, respectively). In both mouse studies, the SPECT images allowed a clear delineation of the radioactivity concentrated over the cortex area of the kidneys, whereas the pelvis and the pelviureteral junction (1 mm) appeared as cold areas. The quantitative data derived from SPECT were in good agreement with the radioactivity counting obtained with a gamma-counter after isolation of the kidneys. In addition, in the mouse injected with (111)In-pentetreotide, the kidney radioactivity distribution seen with SPECT was in agreement with the ex vivo autoradiograms of the isolated kidneys. CONCLUSION: The phantom studies showed a clear improvement of the spatial resolution over the results reported in the literature with other dedicated small-animal SPECT systems, especially in cold-rod phantom studies. The increased performance can be ascribed to the high stability of the system with regard to the statistical noise present in the acquired data. The mouse studies showed that this system will be most useful for in vivo high-resolution SPECT and quantitative biodistribution studies in rodents, even with medium-energy radioisotopes that are difficult to image, such as (111)In.

Animals↗
PubMed1989

Assessment of milk transfer coefficients for use in prediction models of radioactivity transport.

The transfer coefficient (Fm) which is widely used to predict the fraction of ingested radionuclides found in milk is an important parameter for modelling. The accuracy of estimates can be improved by considering the following factors that influence the Fm; (1) the physical-chemical form of the radionuclide in the feed of cows, (2) the hay to concentrate ratio of cows diets and (3) correcting for a steady state situation for feed intake and milk concentrations. Factors such as stable element intake, soil intake, milk production rate, metabolic rate and inhalation do not appear to have significant effects upon the transfer coefficient.

Accidents↗
PubMed1993

Absorption and accumulation of cadmium, lead and mercury from foods by rats.

The purpose of this study was to estimate the apparent absorbability of cadmium (Cd), lead (Pb) and mercury (Hg) from different foods by young rats when these elements occur intrinsically. The study consisted of three independent experiments. In the first experiment rats were fed a casein control diet, a corn-silage diet or an activated-sludge diet. Although the amount of Cd, Pb and Hg ingested from the sludge diet was orders of magnitude higher than that from the casein or corn-silage diet, the absorption of the metals was significantly less (P < 0.02) because these were present as poorly-soluble phosphates. In the second experiment, rats were fed either a commercial fish-meal control diet or an experimental fish-meal diet, with or without the addition of sodium phytate, based on catches from metal-polluted waters. No reduction in absorption resulted from the diet containing phytate as compared with the diet without phytate. The third experiment used the radioactive tracers Cd-115m, Pb-210 and Hg-203 intrinsically incorporated individually into maturing corn ears, on which the three experimental diets were based. The liver and kidney were the main target organs for all three elements (liver: Cd 0.6%, Pb 1.4% and Hg 0.6%; kidney: Cd 0.8%, Pb 0.9% and Hg 1.3%).

Administration, Oral↗
PubMed2003

Availability of 99Tc in undisturbed soil cores.

Models for safety assessment of radioactive waste repositories need accurate values of the soil-to-plant transfer of radionuclides. In oxidizing environments, (99)Tc is expected to occur as pertechnetate ((99)TcO(4)(-)). Due to its high mobility, leaching of this element in the field might be important, potentially affecting the reliability of estimated transfer parameters of (99)Tc as measured in closed experimental systems such as hydroponics or pot experiments. The aim of this experiment was to measure the leaching of (99)Tc in undisturbed irrigated soil cores under cultivation as well as plant uptake and to study the possible competition between the two transfer pathways. Undisturbed soil cores (50 x 50 cm) were sampled from a Rendzic Leptosol (R), a colluvial Fluvic Cambisol (F) and a Dystric Cambisol (D) using PVC tubes (three cores sampled per soil type). Each core was equipped with a leachate collector at the bottom, allowing the monitoring of (99)Tc leaching through the cores. Cores were placed in a greenhouse and maize (Zea mays L., cv. DEA, Pioneer) was sown. After 135 d, maize was harvested and radioactivity determined in both plant and water samples. Results showed that during the growing period, leaching of (99)Tc was limited, due to the high evapotranspiration rate of maize. After harvest, leaching of (99)Tc went on because of the absence of evapotranspiration. Effective uptake (EU) of (99)Tc in leaves and grains was calculated. EU reached 70% of the input in the leaves and was not significantly different among soils. These results confirmed those obtained from pot experiments, even though leaching was allowed to occur in close-to-reality hydraulical conditions. As a consequence, it was concluded that pot experiments are an adequate surrogate for more complex "close-to-reality" experimental systems for measuring transfer factors.

Biological Availability↗
PubMed1984

Metabolism of cerebrosides and sulfatides in subcellular fractions of developing rat brain.

Previous studies on myelinating rat brain indicated that microsomes, Golgi-enriched and cytosol fractions may process galactolipids destined for myelin. To extend these findings we labeled brain galactolipids in vivo and determined the specific radioactivity of cerebrosides and sulfatides in several subcellular fractions. 17-day-old rats were treated by intracranial injection with [14C]galactose 60 min prior to and [3H]galactose 15 min prior to killing. Subcellular fractions were prepared from brain stem, and concentrations of cerebrosides and sulfatides were determined, their radioactivity measured and the 3H/14C ratio compared. Our results showed that the heavier Golgi-enriched fraction (designated Fraction 2) is unique in its low galactolipid content and high specific radioactivities of cerebrosides and sulfatides. The low ratio of the specific activity of cerebroside to that of sulfatide in Fraction 2 compared to other fractions indicates that it may be the site of most rapid conversion of newly synthesized cerebrosides to sulfatides. The specific radioactivities of cerebrosides and sulfatides in cytosol are intermediate between those in Golgi-enriched Fraction 2 and microsomes and those in myelin, consistent with the role postulated for cytoplasmic elements in the transport of cerebrosides and sulfatides to myelin.

Animals↗
PubMed2004

Distribution and flux of 238Pu, 239,240Pu, 241Am, 137Cs and 210Pb to high arctic lakes in the Thule district (Greenland).

Environmental samples (soil, sediment and lake water) in the Thule area (NW Greenland) have been studied to assess the contamination of radionuclides originating from a nuclear weapons accident (the Thule accident in 1968). Four lakes were chosen at different distances from the point of impact with the Thule air base community situated in between. The sedimentation rates in the lakes varied from 0.4 mm a(-1) (5 mg cm(-2) a(-1)) to 1.6 mm a(-1) (82 mg cm(-2) a(-1)). With these sedimentation rates, it is not possible to resolve the (239,240)Pu global fallout peak from a possible (239,240)Pu "accident" peak in the sediment depth profiles. However, the (239,240)Pu/(137)Cs and the (238)Pu/(239,240)Pu ratios agreed well with global fallout ratios, indicating that plutonium originating from the accident had not reached these lakes. This also indicates that the Thule air base community has probably only been exposed to radionuclides from the accident to a very limited extent. A limited study showed that (210)Pb could not be used as a normalizing nuclide to explain the transport of transuranic elements from the catchment area to the lake, i.e. (210)Pb has a different transport mechanism from that of the transuranic elements studied in this investigation.

Arctic Regions↗
PubMed2006

Formation of silver nanoparticles in poly(perfluorosulfonic) acid membrane.

The formation of silver nanoparticles by chemical reduction of Ag+-loaded Nafion-117 membrane with NaBH4 was studied using radioactivity tagged ions. The counterion-exchange method (Ag(m)+ <--> Na(s)+) was used to obtain a membrane sample with a varying proportion of Ag+ ions. The X-ray elemental mapping across the thickness of the membrane by energy-dispersive X-ray spectrometer attached to the environmental scanning electron microscope (ESEM/EDAX) indicated that Na+ and Ag+ were uniformly distributed in the membrane samples before reduction. The average size of nanoparticles formed after reduction was found to be 15 +/- 3 nm, irrespective of the concentration of silver ions present in the membrane before reduction. Energy-dispersive X-ray fluorescence (EDXRF) analyses of the membrane samples, carried out before and after reduction, indicated that the Ag concentration on the membrane surface was considerably increased after reduction. EDXRF measurements of the membrane samples, obtained from reduction carried out in a dead end cell, indicated that Ag nanoparticles were formed only on the membrane surface exposed to NaBH4 solution. Reduction carried out with NaBH4 tagged with 22Na showed that the formation of Ag nanoparticles involved exchange of Ag+ ions from ion-exchange sites in the interior of the membrane with Na+ ions, followed by reduction of Ag+ ions with BH4- ions at the surface of membrane. The study of self-diffusion of water, Na+, and Cs+ ions in the membrane loaded with Ag nanoparticles indicated that formation of Ag nanoparticles did not affect the diffusional transport properties of the membrane. The ion-exchange capacity and water uptake capacity were also not affected by the formation of Ag nanoparticles in the membrane. The spatial distribution of Ag nanoparticles across the thickness of the membrane obtained by ESEM/EDAX showed that Ag nanoparticles were confined to a few-micrometer surface layer of the membrane. Based on these observations, an attempt has been made to explain the mechanism of the formation of Ag nanoparticles in the membrane.

Journal Article↗
PubMedDate not supplied

Radiolabeled microorganisms: comparison of different radioisotopic labels.

Radioactively labeled microorganisms are very useful in assessing the in vitro phagocytic capability of human granulocytes and macrophages. Since microorganisms contain amino acids and nucleic acids, they can be radiolabeled by addition of radioactive amino acid and/or nucleic acid components to the culture medium. The isotopes 3H, 14C, 32P, 35S, and 75Se-have been used for bacterial radiolabeling. All of these commonly used isotopes with the exception of 75Se are beta emitters; 75Se is a gamma emitter. The half-lives of these isotopes vary from 14 days for 32P to 5,730 years for 14C. Because of the differences in their physical properties, they pose very different handling problems and require different kinds of safety precautions. In the event of either external or internal contamination, beta emitters deliver a larger localized radiation dose than do gamma emitters. In the case of internal contamination, the radiation dose increases with increases in the half-life of the radioactive isotope. Gamma radiation, on the other hand, is more penetrating than are beta particles and thus a gamma emitter requires appropriate shielding. Both the cost and the special problem of manipulation associated with these radioactive chemicals should be carefully considered before deciding which radioisotope is preferable for the labeling of microorganisms in the laboratory. In spite of the limitations of 75Se as a nonphysiologic element, it offers the simplest methods of handling among the isotopes considered in this review.

Bacteria↗
PubMed1983

Measurement techniques for radium and the actinides in man at the Center for Human Radiobiology.

Various techniques are employed to determine the amounts, retention, and distribution of radioactivity in human subjects in vivo. The principal method is gamma-ray spectrometry with large NaI(Tl) scintillation crystals ("whole-body counting"). The geometries used include an arc of 1.5-m radius in which all parts of the body are roughly equidistant from the detector, a reclining chair and a flat bed with detectors placed above and below the subject. When a sufficient amount of radioactivity is present in a subject, scanning techniques assist in determining its distribution in the body. Specialized instruments such as a xenon-filled proportional counter and a dual-crystal (phoswich) detector are used to measure low-energy photon emitters, primarily plutonium and americium. americium. There are three primary methods of calibrating the detectors. The first is analytical, in which a rigorous mathematical treatment is employed; the second involves the administration of tracer amounts of radioactivity to human volunteers; the third consists of determining detector response to known amounts of radioactivity in a phantom. All three methods can be intercompared, and further evaluated by comparing the results of measurements in vivo with those of postmortem analyses. For both radium and thorium cases measured in vivo, the interpretation of the results is complicated by the fact that neither radium nor thorium emit gamma rays of any consequence. Instead, the observed gamma rays result from the decay of 214Bi (RaC) and 208Tl (ThC"), respectively. Since each of these nuclides is preceded in the decay chain by an isotope of the noble gas radon, some of which is exhaled, its activity is not equal to that of the parent radium or thorium. Therefore, breath samples are collected to determine the exhalation rate of the precursor isotope, 222Rn (radon) or 220Rn (thoron). The total body content is then the sum of the gamma activity and the exhaled radioactivity, referred to as the retained and emanating fractions, respectively.

Actinoid Series Elements↗
PubMed2001

Non-combustible waste vitrification with plasma torch melter.

Non-combustible radioactive wastes generated from Nuclear Power Plants (NPPs) are composed of concrete, glass, asbestos, metal, sand, soil, spent filters, etc. The melting tests for concrete, glass, sand, and spent filters were carried out using a 60 kW plasma torch system. The surrogate wastes were prepared for the tests. Non-radioactive Co and Cs were added to the surrogates in order to simulate the radioactive waste. Several kinds of surrogate prepared by their own mixture or by single waste were melted with the plasma torch system to produce glassy waste forms. The characteristics of glassy waste forms were examined for the volume reduction factor (VRF) and the leach rate. The VRFs were estimated through the density measurement of the surrogates and the glassy waste forms, and were turned out to be 1.2-2.4. The EPA (Environmental Protection Agency) Toxicity Characteristic Leaching Procedure (TCLP) was used to determine the leach resistance for As, Ba, Hg, Pb, Cd, Cr, Se, Co, and Cs. The leaching index was calculated using the total content of each element in both the waste forms and the leachant. The TCLP tests resulted in that the leach rates for all elements except Co and Cs were lower than those of the Universal Treatment Standard (UTS) limits. There were no UTS limits for Co and Cs, and their leach rate & index from the experiments were resulted in around 10 times higher than those of other elements.

Chemical Phenomena↗
PubMed1994

Future directions for establishing mineral/trace element requirements.

The amount of an element needed to prevent frank deficiency may not be sufficient to support optimal nutrition, but amounts to support optimal nutrition have not been established. Minerals and trace elements are toxic in excess and the interval between the required and toxic amount of some elements is narrow. Thus, lower and upper limits of an optimal range must be established. Before establishing dietary recommendations to support optimal nutriture for minerals, we need (1) sensitive and reliable methods for assessing status of most elements and (2) a better understanding of the influence of nutrient and non-nutrient components of diets upon requirements. Functions such as immune function, anti-oxidant status, muscle strength, glucose metabolism, and blood clotting can be affected by inadequate or excessive amounts of an element and may be more sensitive than specific status indices. Since such functions are not specific, studies must be designed so that a cause and effect relationship between the mineral and the functional index can be established. Two approaches to mineral status assessment may be both sensitive and specific: (1) tests of metalloenzyme function and (2) tracer studies using stable isotopes of minerals. Not only can stable isotopes be used to follow the metabolic fate of a mineral without exposure to radioactivity, they can be used in conjunction with compartmental modeling to predict kinetics and pool sizes in tissues not accessible in humans.

Absorption↗
PubMed1996

Role for sterol regulatory element binding protein in the regulation of farnesyl diphosphate synthase and in the control of cellular levels of cholesterol and triglyceride: evidence from sterol regulation-defective cells.

In order to define the factors involved in the regulation of farnesyl diphosphate (FPP) synthase, we used sterol regulation-defective (SRD) cell lines that constitutively express either high (SRD-2) or low (SRD-6) levels of transcriptionally active sterol regulatory element binding protein (SREBP). FPP synthase mRNA levels were high in SRD-2 cells and low in SRD-6 cells and were unaffected by the addition or removal of sterols from the media. In contrast, the mRNA levels in parental CHO-7 cells were regulated by sterols. SRD-2, SRD-6, and CHO-7 cells were also transiently transfected with plasmids containing FPP synthase promoter-reporter genes. Reporter gene activity was significantly higher in SRD-2 cells than in either SRD-6 or CHO-7 cells, consistent with a higher rate of transcription of the reporter gene in SRD-2 cells. The high expression of the reporter gene in SRD-2 cells was not observed when the FPP synthase promoter contained a three base pair mutation within an SREBP binding site, termed sterol regulatory element-3 (SRE-3). These observations are consistent with the hypothesis that high levels of transcription of the FPP synthase gene are dependent on the availability of transcriptionally active SREBP. We also demonstrate that the incorporation of radioactive acetate into both cholesterol and fatty acids was enhanced in SRD-2 cells as compared to CHO-7 or SRD-6 cells. Finally, we demonstrate that the concentrations of cholesterol, cholesteryl ester, and triglyceride were all significantly elevated in SRD-2 cells. We conclude that SREBP is involved not only in the regulation of FPP synthase and cholesterogenesis but also in fatty acid and triglyceride synthesis.

Acetates↗
PubMed1997

The ecosystem study on Rongelap Atoll.

During the 1950's and 1960's, the Laboratory of Radiation Biology at the University of Washington carried out an intensive study of this Atoll, which was contaminated with radioactive fallout from the "Bravo shot" in 1954. This study involved many aspects of the environment and the plant and animal life: soils, land plants, marine life, birds, geology and hydrology, and human diets as well. In much of the research, the fortuitiously present radioactive isotopes, especially 137Cs and 90Sr, were tracers. Although the term "ecosystem study" was not in vogue at that time, it is clear that this was an early use of the ecosystem approach. Soil types and their development, the distribution of mineral elements in plants and soils, including predominant radionuclides, distribution and growth of native terrestrial plants in relation to topography and salinity, some aspects of the human diets, micronutrient nutrition of the coconut palm, island and islet development and stability, were given attention in the studies. Some of the findings in the various areas of study will be presented and discussed.

Animals↗
PubMed2001

Analysis of radioactive particles from the Kola Bay area.

Two types of radioactive particle were identified in marine sediment and lichen samples collected from the Kola Bay, NW Russia. The particles were identified by means of gamma-ray spectrometry and autoradiography, separated and subjected to various analysis techniques. Several complementary techniques are needed to characterise particle properties thoroughly. 137Cs was present in the sediment matrix in large (approximately 100 microns) greenish particles that were most probably pieces of paint. Although their element composition was heterogeneous, 137Cs was found to be evenly distributed. 60Co in the lichen matrix was present in small (approximately 1 micron) particles. No U or transuranium elements were detected in either type of particle.

Autoradiography↗
PubMed1994

Metabolic and toxicological studies on cobalt.

In this study, the following in vitro and in vivo experiments were carried out: (a) Rats were exposed to the radionuclide 57Co2+ ions in single intraperitoneal or intravenous doses (from 10 ng to 1 mg Co/rat) or to 50 ng Co/rat/day through drinking water for 109 days. The target tissue for cobalt depended on the dosage and route of administration (e.g. lung, kidney or bone). Excretion took place mainly through urine (i.p. and i.v. administration) or feces. At 24 h, testis of rats i.v. injected with 10 ng Co/rat contained 0.056% of the dose, with approximately 0.036% in the epididymus, and 0.08% in the deferens. No radioactivity was found in the germinal cells. (b) In vitro incorporation of cobalt in rat sperm. Cobalt enters the germinal cells suggesting that in vivo barriers against the incorporation of the element in sperms may occur. (c) Dose-effect relationships in BALB/3T3 cell cultures exposed to concentrations of cobalt from 1000 to 1 microM of Co2+. Cobalt induced a dose dependent cytotoxic response. At 10 microM, cell growth was reduced to about 30%. No inhibition was found at 1 microM. Morphological transformation assays gave negative results when the cells were exposed to 1000 microM of cobalt.

3T3 Cells↗