Radioisotope Analysis Research Articles

A Defensin Defense Against Diabetes?

The treatment of diabetes has focused on either replacing insulin or increasing sensitivity to it. Noting that plasma concentrations of human neutrophil α-defensins (HNPs) activate Akt, a component of the insulin signaling pathway, and that severe bacterial infections (which are associated with increased plasma HNPs) are often accompanied by hypoglycemia, Liu et al . investigated the role of HNPs in regulating hepatic glucose production. Intravenous administration of HNP-1 decreased blood glucose concentration in both wild-type mice and Zucker diabetic fatty rats [ZDF rats, a model of type II (insulin-resistant) diabetes]. Under conditions in which hyperinsulinemia was maintained in ZDF rats by means of the continuous infusion of insulin, HNP-1 increased the rate of glucose infusion required to maintain euglycemia. Radioisotopic analysis indicated that this depended on a decrease in glucose production, rather than an increase in uptake by skeletal muscle. HNP-1 inhibited pharmacologically stimulated gluconeogenesis and glycogenolysis in isolated mouse hepatocytes and also inhibited the pharmacologically stimulated increase in mRNAs encoding the gluconeogenic enzymes glucose-6-phosphatase and phosphoenoylpyruvate carboxyl kinase (PEPCK) and activation of a gene reporter under the control of the PEPCK promoter. Like insulin, HNP-1 and -2 stimulated phosphorylation of Akt and FoxO1 in hepatoma cells and primary mouse hepatocytes. Whereas insulin stimulated the phosphorylation of IRS1 but not that of c-Src, HNP-1 stimulated the phosphorylation of c-Src but not that of IRS-1. Furthermore, c-Src activation was required for the effects of HNP-1 on glucose-6-phosphatase mRNA expression and gluconeogenesis but not for those of insulin. Thus, the authors conclude that HNP-1 can inhibit hepatic glucose production through a pathway distinct from that mediated by insulin, a finding that may have implications for the treatment of diabetes. H.-Y. Liu, Q. F. Collins, F. Moukdar, D. Zhuo, J. Han, T. Hong, S. Collins, W. Cao, Suppression of hepatic glucose production by human neutrophil α-defensins through a signaling pathway distinct from insulin. J. Biol. Chem . 283 , 12056-12063 (2008). [Abstract] [Full Text]

Pharmacokinetic Studies in Microdosing and Phase 0 Trials

Pharmacokinetic Studies in Microdosing and Phase 0 Trials

Intracellular localization of natural and modified oligonucleotides in primary human endothelial cells

Intracellular localization of natural and fluorescent-labeled oligonucleotides in primary human endothelial cells was studied by means of fluorescence microscopy and radioisotope analysis. Transport and distribution of oligonucleotides in endotheliocytes depended on their structure and resistance to hydrolysis under the effect of cell nucleases. Modification of 5'-terminal phosphate and 3'-terminal oligonucleotide increased the stability and ensures nuclear localization of oligonucleotides in cells.

Sedimentation rates in relation to sedimentary processes of the Yangtze Estuary, China

Radioisotope analysis and Digital Elevation Model (DEM) method were combined to examine sedimentation rates and associated sedimentary processes in the Yangtze River Estuary. The major depocenter is validated at the delta front sedimentary facies above the normal wave base (NWB), where accumulation exceeds erosion. This alternated sedimentation does not accommodate Pb-210 and Cs-137 measurement, although sedimentation rates of less than 0.2–5.0 cm yr −1 were recorded in the fine-grained (silty) sediments, which were interbedded with coarse-grained (sandy) sediments. However, historical DEM data provide more detailed information on sedimentation in the delta front facies, where accumulation is dominant in the sandy shoals (1.73–8.30 cm yr −1) and delta front slope (5.22 cm yr −1) facies. The DEM data also show that erosion (1.61–7.32 cm yr −1) dominates in the northern estuarine distributaries, and accumulation (3.01–4.97 cm yr −1) prevails in the southern ones, primarily owing to the superimposed runoff and ebb tidal currents. Pb-210 and Cs-137 measurements reveal sedimentation rate from 2.0 cm yr −1 to 6.3–6.6 cm yr −1 in the delta front slope facies, which progressively decreases to <0.8 cm yr −1 in the prodelta facies and is unmeasurable in the delta-shelf transition zone. DEM analysis detects minor erosion in the delta front slope and prodelta facies, although accumulation predominates there. The present sedimentological database will be useful for estuarine environmental assessment after the Three-Gorges Dam is completed in 2009.

The Villalbeto de la Peña meteorite fall: I. Fireball energy, meteorite recovery, strewn field, and petrography

An impressive daylight fireball was observed from Spain, Portugal, and the south of France at 16h46m45s UTC on January 4, 2004. The meteoroid penetrated into the atmosphere, generating shock waves that reached the ground and produced audible booms. The associated airwave was recorded at a seismic station located 90 km north of the fireball trajectory in Spain, and at an infrasound station in France located 750 km north-east of the fireball. The absolute magnitude of the bolide has been determined to be -18 ± 1 from a casual video record. The energy released in the atmosphere determined from photometric, seismic, and infrasound data was about 0.02 kilotons (kt). A massive fragmentation occurred at a height of 28 ± 0.2 km, resulting in a meteorite strewn field of 20 ± 6 km. The first meteorite specimen was found on January 11, 2004, near the village of Villalbeto de la Pena, in northern Palencia (Spain). To date, about 4.6 kg of meteorite mass have been recovered during several recovery campaigns. The meteorite is a moderately shocked (S4) L6 ordinary chondrite with a cosmic-ray-exposure age of 48 ± 5 Ma. Radioisotope analysis shows that the original body had a mass of 760 ± 150 kg, which is in agreement with the estimated mass obtained from photometric and seismic measurements.

LINEAR ACCELERATOR MASS SPECTROMETRY WITH PIXE CALIBRATION

AMS is commonly used in radioisotope analysis because it can detect isotopes down to levels of 10-15 by abundance, but applications for trace element analysis are few. Therefore, we propose a new kind of AMS for trace element analysis using a linear accelerator (LINAC), an Electron Cyclotron Resonance Ion Source (ECRIS), and calibration methods with PIXE analysis. Abundance ratios of each element measured by PIXE are applied to create distribution charts of particles and charge states, and these charts are used for quantitative analysis. We report the concepts behind our AMS and calibration methods in this paper.

Interface of a particle collector with an on-line electrochemically-modulated separation system for analysis of airborne radioisotopes

The International Monitoring System is part of the global verification system of the Comprehensive Nuclear-Test-Ban Treaty and comprises an atmospheric radioactivity monitoring network of 80 particulate stations, 40 of which are to be equipped with noble-gas-detection capability. The network is supported by 16 radionuclide laboratories. The equipment has to be tailored to different environments and its reliability is proving to be an operational challenge.

Anabolic Effect of Natural and Synthetic Antioxidants

The order of responses of cell systems of organs and changes in the content of some proteins of mouse and dog blood in response to addition of natural (alpha-tocopherol) and synthetic (ionol) antioxidants was studied at the whole-body level using ERP spectroscopy, radioisotope analysis, and chemiluminescence technique. Responses were evaluated by the temporary and concentration-dependence changes in the activity of ribonucleotide reductase and the rate of protein and DNA synthesis in organs of mice, as well as by the changes in the pools of Fe3+ -transferrin and Cu2+ -ceruloplasmin in blood and the antiradical activity of blood plasma of dogs and mice. During the first 24 h of exposure to alpha-tocopherol, the activity ribonucleotide reductase in bone marrow rapidly increased, whereas the activity of this enzyme and the rate of DNA synthesis in the thymus and spleen were suppressed by 30-50% compared to the control. The changes in these parameters had a phase mode with maxima on days 2-3 and 6-8. The stimulatory effect of the antioxidant on the processes of synthesis was concentration-dependent. We found that the optimal stimulation of the synthesis of deoxyribonucleotides, DNA, and protein was achieved by single administration of alpha-tocopherol at a dose of 20 mg per dog with an average weight of 15 kg and 17 mg/kg in the case of mice. Single or repetitive administration of higher doses of alpha-tocopherol was either ineffective or even suppressed the synthesis of DNA and deoxyribonucleotides. Ionol administered at a dose of 60 mg/kg increased DNA and protein synthesis in mouse organs in 2-4 and 1.2-1.5 times, respectively, compared to the control. It was also shown that single and repetitive administration of alpha-tocopherol to dogs increased the pool of Fe3+ -transferrin and Cu2+ -ceruloplasmin in blood in 2-3 times and by 20-30%, respectively, compared to the control. It is suggested that changes in Fe3+ -transferrin pool in peripheral blood may be used for evaluation of the stimulatory effect of antioxidants on the synthesis of macromolecules in organs and for the determination of dependence of this effect on the concentration of antioxidants.

Radioisotopic evaluation of bone repair after experimental surgical trauma

Scientific approach of the bone reaction after surgical procedures provides valuable information on methods and techniques. The purpose of this study was to follow this process using a radioisotope marker of bone remodelling. Two bone cavities were created (one for every tibia) in adult Wistar male rats using a 0.5 mm spherical burr; left tibial cavities were filled with bovine freeze-dried bone; the right ones were left unfilled for control. Scintigrams were done with sodium methylene diphosphonate (MDP) labelled with radioactive pertechnetate (99mTcO4-) to evaluate the inflammatory response and the local osteoblastic activity. The evolution of bone repair was additionally evaluated by light microscopy. Our results have shown that the highest bone activity was recorded between the 7th and the 14th day after surgery. The morphological analysis confirmed the results obtained with radioisotope analysis and did not reveal significant differences regarding the evolution of bone repair between the filled and the unfilled defects. We confirmed that 99mTc -MDP is a valuable tool to study bone repair, as it was able to show subtle alterations of bone activity even in lesions as small as those created herein (0.5 mm wide, 0.5 mm deep).

Efficient three-step, two-color ionization of plutonium using a resonance enhanced 2-photon transition into an autoionizing state

Resonance ionization mass spectrometry (RIMS) has proven to be a powerful method for isotope selective ultra-trace analysis of long-lived radioisotopes. For plutonium detection limits of $\rm 10^{6}$ to $\rm 10^{7}$ atoms have been achieved for various types of samples. So far a three-step, three-color laser excitation scheme was applied for efficient ionization. In this work, a two-photon transition from an excited state into a high-lying autoionizing state, will be presented, yielding a similar overall efficiency as the three-step, three-color ionization scheme. In this way, only two tunable lasers are needed, while the advantages of a three-step, three-color excitation (high selectivity, good efficiency and low non-resonant background) are preserved. The two-photon transition has been characterized with respect to saturation behavior and line width. The three-step, two-color ionization is a possibility for an improved RIMS procedure.

In vitro microleakage of adhesive-sealed dentin with lactic acid and saliva exposure: a radio-isotope analysis.

The aim of this study was to evaluate the dentin-protective potential of two dentin-bonding systems (Syntac and Clearfil SE Bond) on artificial saliva and lactic acid exposure. Radiochemical analysis in combination with polarization-microscopy was used in the current study. Different applications in MOD preparations in irradiated human molars were compared. Untreated cavities and cavities covered with flowable resin served as controls. Forty-eight specimens were immersed in artificial saliva (pH 7.5), 48 in lactic acid (pH 4). Activity of (32)P was measured between days 1 and 21 and loss of mineralized tissue was estimated. In lactic acid, cavities sealed with single bond, double bond or bond plus cavity sealer application resulted in significantly lower mineralized tissue loss compared to negative controls (p < 0.05). Upon both saliva and lactic acid exposure, bonding plus sealer application proved to be the most protective treatment (p < 0.05). Based on these in vitro findings it may be advisable to use a filled cavity sealer or a flowable resin to protect dentin from demineralization. The radiochemical analysis appeared to be valuable in evaluating the protective potential of bonding agents against dentin demineralization.

Collision cell chemistry for the analysis of radioisotopes by inductively coupled plasma mass spectrometry

The application of reaction and collisional chemistry with inductively coupled plasma mass spectrometry for the measurement of 90Sr, 135Cs, 137Cs, 210Pb, and 226Ra were investigated. Improvement in sensitivity of all the aforementioned radioisotopes was found by optimization of the collision cell parameters. It was demonstrated that the measurements of radiocesium and radiostrontium require different collision cell parameters if they are measured in the presence or absence of Ba and Zr. The detection limits were improved by a factor of 100, 33, 22, 500, and 50 for 90Sr, 135Cs, 137Cs, 210Pb, and 226Ra, respectively.

Ultratrace analysis and isotope ratio measurements of long-lived radioisotopes by resonance ionization mass spectrometry (RIMS).

Resonance Ionization Mass Spectrometry (RIMS) is a sensitive and selective method for ultratrace analysis of long-lived radioisotopes and isotope ratio measurements. It provides extremely high isobaric suppression and good overall efficiency. The experimental limits of detection are as low as 10(6) atoms per sample and isotopic selectivities of 5x10(12) have been obtained. The widespread potential of RIMS, using different experimental arrangements, is demonstrated for the determination of the radiotoxic isotopes Pu-238 to Pu-244 and Sr-89/Sr-90 in various environmental samples as well as for Ca-41 in nuclear reactor components and biomedical samples.

Historical Assessment of the Impacts of Chemical Contaminants in Sediments on Benthic Invertebrates in the Tidal Passaic River, New Jersey

A historical impact assessment was conducted for chemical contaminants in sediments of the tidal Passaic River in northern New Jersey. The assessment was based on sediment cores collected from 1990 to 1995. Each sediment core was segregated into fractions and the fractions dated using radioisotope analysis. Chemical concentrations, including a variety of metals and organic compounds, were estimated by decade for most of the 20th century in five reaches of the River. The chemical data for each decade were compared to available benchmark sediment quality values that represent levels of chemicals that may be toxic to benthic invertebrates in estuarine systems. Benchmark exceedances in the River were then calculated and characterized spatially and temporally using quantitative Geographic Information System (GIS) analyses, and the area of “impacted” sediments was calculated for each chemical and decade. Results of this assessment suggest that the ability of Passaic River sediments to support “normal” benthic invertebrate populations was limited by sediment contaminants throughout the 20th century. Conditions have improved somewhat since the 1950s, although impacts to benthic populations remain from several metals and organic compounds despite some overall improvements in sediment quality in recent years.

Sampling of sub-seafloor aquifers by a temporary well for CFC age dating and natural tracer investigations

Based on a sediment vibro corer, a tool for the sampling of sub-seafloor groundwater aquifers has been developed and successfully deployed in a coastal area of the western Baltic. The device was designed to obtain pure groundwater samples from coarse sediments to be used for tracer investigations and CFC age dating. Operated from a medium size research vessel, a well pipe tipped with a filter segment is vibrated into the sediment down to the aquifer. Groundwater entering the filter is pumped to the ship by a conventional submersible pump situated in the well's filter tip. Groundwater is continuously analysed on board for O 2, salinity, pH, Eh and temperature, prior to sampling for CFC and radioisotope analysis. All parameters indicate that pure groundwater had been obtained. CFC concentrations are very low suggesting that the groundwater of this shallow sub-seafloor aquifer recharged prior to 1950. This finding is in accordance with other hydrogeological evidence that this aquifer, located only 4–5 m below the seafloor, is connected to fairly deep confined sandy aquifers on land of Pleistocene or Miocene age. Applying the method described, it is possible to obtain sufficient sample volumes for analyses of natural groundwater tracers such as radon-222 and CFCs which can be used to trace submarine groundwater discharge as well as the origin of groundwater in such environments.

Trace analysis of plutonium in environmental samples by resonance ionization mass spectroscopy (RIMS)

Resonance ionization mass spectroscopy (RIMS) is well suited for trace analysis of long-lived radioisotopes in environmental, biological and technical samples. By multiple resonant laser excitation and ionization of the elemental atoms under investigation, an extremely high element selectivity can be achieved. In addition, isotope selectivity is obtained by subsequent mass analysis. The excellent sensitivity results from the large atomic cross-sections in the excitation–ionization process and the good detection efficiency for ions. The element selectivity of RIMS allows a simplified procedure for the chemical preparation of the samples compared to the requirements of thin sources for α-spectroscopy. Various samples have been determined by RIMS with respect to their content and the isotopic composition of plutonium in the ultra-trace regime. A detection limit of 10 6 to 10 7 plutonium atoms has been achieved for all isotopes, independent of their half-life and decay mode. For 239Pu, this value is distinctly below the radiometric detection limit.

Discriminating between Sources of Arsenic in the Sediments of a Tidal Waterway, Tacoma, Washington

Various industries located along the Hylebos Waterway in Tacoma, WA, and runoff from slag used for road ballast are potential sources of elevated arsenic concentrations found in the waterway sediments. To discriminate between specific sources of As to the waterway, the history of arsenic deposition was reconstructed using 137Cs sediment age-dating combined with characterization of arsenic solid phases. In a sediment core collected near a former powdered metals facility, As occurred primarily in metal sulfides, reaching peak concentrations in the mid-1950s, consistent with the operational history of that facility. In a second core collected near a pesticide plant that historically discharged soluble arsenic, total arsenic was present predominantly as surface-bound species in sediment pre-dating the mid-1980s, decreasing in recent sediments coincident with initiation of remedial measures in 1981. Ferro-alloy and smelter slags were recent and optically distinguishable. The combination of optical microscopy and electron and laser-ion microprobe techniques in conjunction with historical information and radioisotopic analysis provides a powerful tool to differentiate between metal sources to sediments.

Application of laser mass spectrometry for trace analysis of plutonium and technetium / Anwendung der Lasermassenspektrometrie zur Spurenanalytik von Plutonium und Technetium.

Resonance ionization mass spectrometry (RIMS) is a highly selective and sensitive method for trace analysis of radiotoxic elements in environmental, biological or technical samples. By multiple resonant laser excitation and ionization of the element under investigation, an extremely high element selectivity is achieved. Additionally, isotope selectivity is obtained by subsequent mass analysis in a magnetic, time-of-flight or quadrupole mass spectrometer which serves for efficient background suppression as well. High sensitivity results from the large optical cross sections in the photo-ionization process and the high detection efficiency for ions. The outstanding element selectivity of RIMS permits a simplification of the chemical separation method. RIMS has been used for ultra-trace analysis of long-lived radioisotopes of Pu and Tc in various samples. The detection limit determined experimentally is of the order of 10 6 atoms per sample. For some of the most important long-lived radioisotopes, this value is distinctly below the radiometric detection limit.

Precision and resolution in mammalian chronostratigraphy: principles, practices, examples

ABSTRACT This paper addresses the principles and practices applicable to developing highly resolved correlations in mammalian chronostratigraphy. A FAD (first appearance datum) is only as sound as the precision and accuracy of the LSDs (lowest stratigraphic datums) of which it is composed. Precision in boundary definition stems from improved analytical procedures in morphological as well as radioisotopic analysis, magnetostratigraphic correlations, and consideration of the completeness of stratigraphic sections. The so-called Hipparion Datum is examined as an example of these topics. More correctly known as the Hippotherium Datum, this event apparently took place at about 10.8 Ma and is resolvable within an interval of about 0.5 my. Discussion of evolutionary rates ends with a proposal for developing a catalog of such rates in geologically young situations in which the ± factors of the radioisotopic ages are less than the intervals being discriminated. These examples then may be compared with those develo...

Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora.

The pathways of short-chain fatty acid (SCFA; acetate, propionate, and butyrate) formation from glucose were determined for the human fecal microbial communities of two subjects. The pathways were identified by radioisotope analysis of the SCFA and CO2 obtained after incubation of fecal suspensions with glucose under 20% CO2 with [1-14C]glucose, [3,4-14C]glucose, or 14CO2. Acetate was chemically degraded to learn the labeling of the methyl and carboxyl carbons. The labeling of CO2 and acetate showed that the major route of glucose catabolism was the Embden-Meyerhof-Parnas pathway, with production of CO2 from pyruvate carboxyl carbon. Labeling of the methyl and carboxyl carbons of acetate by 14CO2 or [3,4-14C]glucose proved that acetate was formed from CO2 by the Wood-Ljungdahl pathway. CO2 reduction accounted for about one-third of the acetate formed by suspensions from subject 1 and about one-fourth of the acetate formed by suspensions from subject 2. Propionate was formed by a CO2 fixation pathway, and butyrate was formed by classical routes of acetyl-S coenzyme A condensation. The amount of CO2 formed from [1-14C] glucose and acetate labeling patterns obtained with the other 14C precursors indicated that the Entner-Doudoroff, transketolase-transaldolase, and heterolactic pathways were not significant. Fermentation of cabbage cellulose by subject 1 followed the same pathways as were used for glucose. The results with suspensions from subject 2 suggested that some radioactive acetate was formed from the C-3 of glucose by the Bifidobacterium pathway.