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Comparison of 99mTc-sestamibi-18F-fluorodeoxyglucose dual isotope simultaneous acquisition and rest-stress 99mTc-sestamibi single photon emission computed tomography for the assessment of myocardial viability.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

Adult↗

Almost twenty years' search of transuranium isotopes in effluents discharged to air from nuclear power plants with VVER reactors.

Airborne effluents of 5 stacks (stacks 1-5) of three nuclear power plants, with 9 pressurized water reactors VVER of 4,520 MWe total power, were searched for transuranium isotopes in different time periods. The search started in 1985. The subject of this work is a presentation of discharge data for the period of 1998-2003 and a final evaluation. It was found that 238Pu, 239,240Pu, 241Am, 242Cm, and 244Cm can be present in airborne effluents. Transuranium isotope contents in most of the quarterly effluent samples from stacks 2, 4 and 5 were not measurable. Transuranium isotopes were present in the effluents from stack l during all 9 years of the study and from stack 3 since the 3rd quarter of 1996 as a result of a defect in the fuel cladding. A relatively high increase of transuranium isotopes in effluents from stack 3 occurred in the 3rd quarter of 1999, and a smaller increase occurred in the 3rd quarter of 2003. In each instance 242Cm prevailed in the transuranium isotope mixtures. 238Pu/239,240Pu, 241Am/239,240Pu, 242Cm/239,240Pu, and 244Cm/239,240Pu ratios in fuel for different burn-up were calculated, and comparison of these ratios in fuel and effluents was performed.

Air Pollutants, Radioactive↗

Helium diffusion through H2O and D2O amorphous ice: observation of a lattice inverse isotope effect.

The diffusion of He through both H2O and D2O amorphous solid water (ASW) has been measured between 55 and 110 K. We find the diffusion rate is dependent on the isotopic composition of the ASW lattice. This lattice isotope effect is the "inverse" of a normal isotope effect in that diffusion is faster in the heavier (D2O) isotope. Transition state theory calculations show that the inverse isotope effect is due to a tight transition state and predominantly arises from the zero-point vibrational energy associated with the frustrated rotational modes of water in the lattice.

Journal Article↗

Effect of Varying CO(2) Partial Pressure on Photosynthesis and on Carbon Isotope Composition of Carbon-4 of Malate from the Crassulacean Acid Metabolism Plant Kalanchoë daigremontiana Hamet et Perr.

Intact leaves of Kalanchoë daigremontiana were exposed to CO(2) partial pressures of 100, 300, and 1000 microbars. Malic acid was extracted, purified, and degraded in order to obtain isotopic composition of carbon-1 and carbon-4. From these data, it is possible to calculate the carbon isotope composition of newly fixed carbon in malate. In all three treatments, the isotopic composition of newly introduced carbon is the same as that of the CO(2) source and is independent of CO(2) partial pressures over the range tested. Comparison with numerical models described previously (O'Leary 1981 Phytochemistry 20: 553-567) indicates that we would expect carbon 4 of malate to be 4 per thousand more negative than source CO(2) if diffusion is totally limiting or 7 per thousand more positive than source CO(2) if carboxylation is totally limiting. Our results demonstrate that stomatal aperture adjusts to changing CO(2) partial pressures and maintains the ratio of diffusion resistance to carboxylation resistance approximately constant. In this study, carboxylation and diffusion resistances balance so that essentially no fractionation occurs during malate synthesis. Gas exchange studies of the same leaves from which malate was extracted show that the extent of malate synthesis over the whole night is nearly independent of CO(2) partial pressure, although there are small variations in CO(2) uptake rate. Both the gas exchange and the isotope studies indicate that the ratio of external to internal CO(2) partial pressure is the same in all three treatments. Inasmuch as a constant ratio will result in constant isotope fractionation, this observation may explain why plants in general have fairly invariable (13)C contents, despite growing under a variety of environmental conditions.

Journal Article↗

Short-term measurement of carbon isotope fractionation in plants.

Combustion-based studies of the carbon-13 content of plants give only an integrated, long-term value for the isotope fractionation associated with photosynthesis. A method is described here which permits determination of this isotope fractionation in 2 to 3 hours. To accomplish this, the plant is enclosed in a glass chamber, and the quantity and isotopic content of the CO(2) remaining in the atmosphere are monitored during photosynthesis. Isotope fractionation studies by this method give results consistent with what is expected from combustion studies of C(3), C(4), and Crassulacean acid metabolism plants. This method will make possible a variety of new studies of environmental and species effects in carbon isotope fractionation.

Journal Article↗

Correlation between the Carbon Isotope Discrimination in Leaf Starch and Sugars of C(3) Plants and the Ratio of Intercellular and Atmospheric Partial Pressures of Carbon Dioxide.

Carbon isotope discrimination (Delta) was analyzed in leaf starch and soluble sugars, which represent most of the recently fixed carbon. Plants of three C(3) species (Populus nigra L. x P. deltoides Marsh., Gossypium hirsutum L. and Phaseolus vulgaris L.) were kept in the dark for 24 hours to decrease contents of starch and sugar in leaves. Then gas exchange measurements were made with constant conditions for 8 hours, and subsequently starch and soluble sugars were extracted for analysis of carbon isotope composition. The ratio of intercellular, p(i), and atmospheric, p(a), partial pressures of CO(2), was calculated from gas exchange measurements, integrated over time and weighted by assimilation rate, for comparison with the carbon isotope ratios in soluble sugars and starch. Carbon isotope discrimination in soluble sugars correlated strongly (r = 0.93) with p(i)/p(a) in all species, as did Delta in leaf starch (r = 0.84). Starch was found to contain significantly more (13)C than soluble sugar, and possible explanations are discussed. The strong correlation found between Delta and p(i)/p(a) suggests that carbon isotope analysis in leaf starch and soluble sugars may be used for monitoring, indirectly, the average of p(i)/p(a) weighted by CO(2) assimilation rate, over a day. Because p(i)/p(a) has a negative correlation with transpiration efficiency (mol CO(2)/mol H(2)O) of isolated plants, Delta in starch and sugars may be used to predict differences in this efficiency. This new method may be useful in ecophysiological studies and in selection for improved transpiration efficiency in breeding programs for C(3) species.

Journal Article↗

Oxygen-18 Content of Atmospheric Oxygen Does Not Affect the Oxygen Isotope Relationship between Environmental Water and Cellulose in a Submerged Aquatic Plant, Egeria densa Planch.

We determined that the oxygen isotopic composition of cellulose synthesized by a submerged plant, Egeria densa Planch., is related to the isotopic composition of environmental water by a linear function, delta(18)O cellulose = 0.48 delta(18)O water + 24.1% per thousand. The observation of a slope of less than 1 indicates that a portion of cellulose oxygen is derived from an isotopically constant source other than water. We tested whether this source might be molecular oxygen by growing plants in the presence of high concentrations of (18)O in the form of O(2) bubbled into the bottom of an aquarium. Cellulose synthesized during this experiment did not have significantly different oxygen isotope ratios than that synthesized by control plants exposed to O(2) of normal (18)O abundance. We propose that oxygen in organic matter recycled from senescent portions of the plant is incorporated into cellulose. Our findings indicate that paleoclimatic models linking the oxygen isotope composition of environmental water to cellulose from fossil plants will have to be modified to account for contributions of oxygen from this or other sources besides water.

Journal Article↗

Fractionation of Carbon Isotopes during Biogenesis of Atmospheric Isoprene.

The stable carbon isotope composition of isoprene emitted from leaves of red oak (Quercus rubra L.) was measured. Isoprene was depleted in (13)C relative to carbon recently fixed by photosynthesis. The difference in isotope composition between recently fixed carbon and emitted isoprene was independent of the isotopic composition of the source CO(2). beta-Carotene, an isoprenoid plant constituent, was depleted in (13)C relative to whole leaf carbon to the same degree as isoprene, but fatty acids were more depleted. Isoprene emitted from leaves fed abscisic acid was much less depleted in (13)C than was isoprene emitted from unstressed leaves. We conclude that isoprene is made from an isoprenoid precursor that is derived from acetyl-CoA made from recent photosynthate. The carbon isotope composition of isoprene in the atmosphere is likely to be slightly more negative (less (13)C) than C(3) plant material but when plants are stressed the isotopic composition could vary.

Journal Article↗

Investigation of the swollen limb with isotope lymphography.

The usefulness of isotope lymphography was evaluated in patients with chronic lower leg swelling. Forty patients (15 male, 25 female, age range 5 months-67 years) were assigned one of six clinical diagnoses based on clinical assessments, venography and lymphography. All the patients and seven normal controls were examined with bilateral isotope lymphography involving subcutaneous injection of 0.15 ml 99mTc-antimony sulphide colloid into the first web space of each foot. The percentage uptake of isotope-colloid in the inguinal lymph nodes at 1 and 2 h was equated with lymphatic function. Highly significant (P = 0.0001) differences existed between the different clinical groups and isotope lymphography discriminated well between oedema of lymphatic and non-lymphatic origin. Isotope lymphography appears to be a safe and useful test of lymphatic function.

Adolescent↗

Deuterium isotope effects as a tool in the study of ethanol oxidation in rat liver microsomes.

The apparent kinetic deuterium isotope effect (I) on the oxidation of ethanol to acetaldehyde by washed rat liver microsomes was measured with (1-R)-[1-2H2, 1-14C]-ethanol (I1) and [1-2H2, 2-14C]-ethanol (I2) as substrates by a competitive technique involving only measurements of radioactivity. The average values were for non-induced rats, I1 = 1.57 and I2 = 2.23. When these two substrates were used with stereospecific enzymes (alcohol dehydrogenase and catalase) a small secondary effect was observed, causing I2 to be about 10% higher than I1. With non-stereospecific systems I2 was much larger than I1, and the values were connected by a simple formula. This relation in combination with use of the inhibitors, sodium azide and thiourea, made it possible to calculate tentatively the contribution to microsomal ethanol oxidation of catalase, a non-identified stereospecific enzyme, and non-stereospecific catalytic systems, as well as the isotope effects of the latter two systems. Measurements were made in microsomes from normal, phenobarbital treated, and acetone treated rats. For the stereospecific component an isotope effect of 1.4-1.5 was calculated for all three groups. For the non-stereospecific enzyme in acetone treated rats a value of 4.0 was found. Both the other groups showed a value about 2.7. The activity of the non-stereospecific system was about twice the normal in barbiturate treated, and 3 times the normal in the acetone treated group, where it contributed 70% of the total activity. The isotope effects on the changes in ethanol oxidation (the 'differential isotope effect') caused by inhibitors and activators were utilized to decide whether inhibitors were specific for a single reaction. Thus azide while inhibiting catalase completely, also inhibited other reactions. The large increase (5-6 times) in rate caused by Fe-ESDTA has an I2 of 1.6, equal to that for oxidation of ethanol by hydroxyl radicals.

Acetone↗

Effect of iron type on kinetics and carbon isotopic enrichment of chlorinated ethylenes during abiotic reduction on Fe(0).

Four samples of two commercially available iron brands used as substrate for iron permeable reactive barriers (PRBs) were tested for suitability for remediation of perchloroethylene (PCE), trichloroethylene (TCE), cis-dichloroethylene (cDCE) and vinyl chloride (VC). Kinetic studies indicate that rates of reaction are enhanced for cDCE and VC on Connelly iron (2.8 x 10(-4) to 6.9 x 10(-4) L/m2/hr and 2.0 x 10(-4) to 9.0 x 10(-4) L/m2/hr, for cDCE and VC, respectively) vs. Peerless iron (3.1 x 10(-5) to 4.6 x 10(-5) L/m2/hr and 2.4 x 10(-5) to 4.1 x 10(-5) L/m2/hr, for cDCE and VC, respectively). Carbon isotopic analyses of the residual chlorinated ethylene (CE) during degradation indicate significant fractionation occurs during reductive dechlorination, with, for example, up to 70% enrichment in carbon isotopic values observed when VC is more than 99% degraded. Comparison of fractionation factors (epsilon) indicates significant differences in carbon isotopic fractionation for different iron types and for different CEs. For the lower CEs (cDCE and VC) in particular, both slower reaction rates and larger fractionation are observed for degradation on Peerless vs. Connelly iron. This is the first study to establish a correlation between the rate of abiotic degradation on Fe(0) and the extent of isotopic fractionation, and the first to confirm consistent differences in these two parameters as a function of iron type. The possibility that these differences in kinetics and carbon isotopic fractionation for cDCE and VC are related to differences in branching ratios between competing hydrogenolysis and beta-elimination reactions during reductive dechlorination on the iron surfaces is discussed.

Environmental Pollutants↗

Osmium isotope heterogeneity in the constituent phases of mid-ocean ridge basalts.

Radiogenic isotope variations in mid-ocean ridge basalts (MORB) are commonly attributed to compositional variations in Earth's upper mantle. For the rheniumosmium isotope system, constituent MORB phases are shown to possess exceptionally high Re/Os (parent/daughter) ratios, consequently radiogenic 187Os is produced from the decay of 187Re over short periods of time. Thus, in the absence of precise age constraints, Os isotope variations cannot be unambiguously attributed to their source, although Re-Os isotope data for constituent minerals can yield crystallization ages, details of equilibration, and initial Os isotope values that relate directly to the mantle source.

Journal Article↗

Oxygen and iron isotope studies of magnetite produced by magnetotactic bacteria

A series of carefully controlled laboratory studies was carried out to investigate oxygen and iron isotope fractionation during the intracellular production of magnetite (Fe(3)O(4)) by two different species of magnetotactic bacteria at temperatures between 4 degrees and 35 degrees C under microaerobic and anaerobic conditions. No detectable fractionation of iron isotopes in the bacterial magnetites was observed. However, oxygen isotope measurements indicated a temperature-dependent fractionation for Fe(3)O(4) and water that is consistent with that observed for Fe(3)O(4) produced extracellularly by thermophilic Fe(3+)-reducing bacteria. These results contrast with established fractionation curves estimated from either high-temperature experiments or theoretical calculations. With the fractionation curve established in this report, oxygen-18 isotope values of bacterial Fe(3)O(4) may be useful in paleoenvironmental studies for determining the oxygen-18 isotope values of formation waters and for inferring paleotemperatures.

Journal Article↗

Rate-limiting steps in cytochrome P-450-catalysed reactions: studies on isotope effects in the O-de-ethylation of 7-ethoxycoumarin.

Primary deuterium isotope effects ranging from 2 to 6 were measured for the O-de-ethylation of 7-ethoxycoumarin catalysed by microsomal and purified cytochrome P-450 isozymes. Interpretation of the observed deuterium isotope effect in terms of the contribution of the C-H bond-cleavage step to the overall rate requires the determination of the intrinsic isotope effect. Evidence is presented that at least one irreversible step occurs before C-H bond cleavage which kinetically divides the cytochrome P-450 reaction cycle into two portions. Intermolecular primary isotope effects are shown to provide kinetic information only about steps following the irreversible step. Consequently, the isotope effect may be a measure of the rate limitation imposed by the C-H bond-cleavage step in the sequence of events following the irreversible step but be totally independent of other slow steps preceding the irreversible step. These results indicate that multiple rate-limiting steps may exist in cytochrome P-450-catalysed reactions.

7-Alkoxycoumarin O-Dealkylase↗

Effect of prostate size and isotope selection on dosimetric quality following permanent seed implantation.

PURPOSE: The aim of this study was to assess retrospectively the influence of prostate size and the effect of isotope selection on implant quality in patients undergoing transperineal ultrasound-guided permanent prostate brachytherapy. PATIENTS AND METHODS: Two hundred forty-eight consecutive patients without prior transurethral resection of the prostate gland underwent permanent seed implantation using either iodine 125 or palladium 103 as monotherapy or a boost following moderate doses of external-beam radiation therapy from January 1998 through November 1999. Postimplant dosimetry was obtained on day 0 using thin slice computed tomography (CT) scans. Dosimetric quality was reported in terms of the following parameters: D90, V100, V150, and V200, where D90 is defined as the minimum dose covering 90% of the prostate volume, and V100, V150, and V200 are defined as the percentage volume of the prostate receiving at least 100%, 150%, and 200% of the prescribed minimal peripheral dose (mPD), respectively. In addition, the urethral dose was evaluated. Preimplant prostate size was divided into the following categories: <20, 20-30, 30-40, 40-50, and >50 cm3. Prostate volume was determined via transrectal ultrasound volumetric study. In addition, within each of the five size categories, the effect of isotope on implant quality was evaluated. RESULTS: No statistically significant volume dependence in D90, V100, or urethral doses was discerned, whereas V150 and V200 were volume dependent. Between isotopes, the following differences in dosimetric quality were statistically significant: V100, V150, V200, and mean and medial urethral dose. 125I implants had higher values of V100 (95% vs. 94%, p = .004) and urethral dose (118% vs. 110% of mPD, p < .001), and 103Pd implants had higher V150 and V200 (57% vs. 51% and 31% vs. 22%, respectively). Only the isotopic differences in V200 persisted for all the volumetric subgroups. There was no significant overall volume dependence based on neoadjuvant hormone use or nonuse for any of the quality parameters analyzed. CONCLUSIONS: The most important indicators of the quality of dosimetric coverage, V100 and D90, were not dependent on preimplant prostate volume or use of neoadjuvant hormones. The mean, median, and maximum urethral doses also showed no dependence on prostate size. Although there were isotopic differences in day 0 dosimetric parameters following permanent prostate brachytherapy, we do not consider the magnitude of any of these differences to be clinically significant.

Aged↗

Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans.

A stable isotope dilution method is described that allows measurement of cholic acid (CA) kinetics, that is, pool size, fractional turnover rate (FTR), and synthesis rate in mice, rats, and humans. Decay of administered [2,2,4,4-2H4]CA enrichment was measured in time in 50-microl plasma samples by gas-liquid chromatography/electron capture negative chemical ionization-mass spectrometry, applying the pentafluorobenzyl-trimethylsilyl derivative. The kinetic data expressed species-dependent differences. The CA pool sizes were 16.8 +/- 2.1, 10.6 +/- 1.2, and 2.4 +/- 0.7 micromol/100 g body weight for mice, rats, and humans, respectively. The FTR values were 0.44 +/- 0.03, 0.88 +/- 0.10, and 0.46 +/- 0.14 per day for mice, rats, and humans. The corresponding synthesis rates were 7.3 +/- 1.6, 9.3 +/- 0.1, and 1.0 +/- 0.2 micromol/100 g body weight per day. The human data agreed well with literature data obtained by conventional isotope dilution techniques. For rats and mice these are the first reported isotope dilution data. The method was validated by confirmation of isotopic equilibrium between biliary CA and plasma CA in the rat. Its applicability was demonstrated by the observation of increased CA FTR and CA synthesis rate in rats fed cholestyramine, which is known to increase fecal bile acid excretion. The presented stable isotope dilution method enables the determination of CA kinetic parameters in small plasma samples. The method can be applied in unanesthetized rodents with an intact enterohepatic circulation and may also be valuable when studying the development of human neonatal bile acid kinetics.

Adult↗

Kinetic deuterium isotope effects on the N-demethylation of tertiary amides by cytochrome P-450.

Liver microsomal cytochrome P-450 readily N-dealkylates N,N-dimethylamides. N-Methyl-N-hydroxymethyl amides were isolated as intermediates and characterized by gas chromatography-mass spectrometry as their trimethylsilyl ethers. Intramolecular kinetic deuterium isotope effects measured for the enzymic N-demethylation of a series of 12 aromatic and aliphatic N-methyl-N-trideuteriomethyl amides, RCON(CH3)CD3, varied from 3.6 to 6.9 but were independent of both amide bond rotation rate and substrate oxidation potential. These values, which represent a lower limit to the intrinsic isotope effect (Dkintrinsic), are significantly larger than those observed for anodic N-demethylation and are consistent with a mechanism involving hydrogen atom abstraction. On the other hand, with N,N-dimethylbenzamide the intermolecular kinetic deuterium isotope effects on Vmax and Vmax/Km were found to be much smaller (1.23 and 1.75, respectively) indicating substantial suppression of the intrinsic isotope effect. Such suppression indicates the occurrence of a rate-limiting step other than the isotopically sensitive step together with a strong commitment to catalysis.

Amides↗

Mechanistic investigations of Escherichia coli cytidine-5'-triphosphate synthetase. Detection of an intermediate by positional isotope exchange experiments.

CTP synthetase from Escherichia coli catalyzes exchange of 18O from the beta gamma-bridge position of [gamma-18O4] ATP into the beta-nonbridge position. This positional isotope exchange occurs in the presence of UTP and MgCl2 but in the absence of NH3. The enzyme also has an ATPase activity in the presence of UTP that occurs under conditions that are identical to those used in the positional isotope exchange experiments. These data provide evidence for the stepwise nature of the reactions catalyzed by CTP synthetase with the initial step involving phosphorylation of UTP by ATP. The relative rate of the isotope exchange reaction is approximately 3 times faster than the ATPase reaction, but the isotope exchange rate is approximately 3% of the overall rate in the presence of NH3. These results are consistent with the ATPase reaction involving attack of water on the phosphorylated intermediate (4-phospho-UTP). The positional isotope exchange reaction is independent of the UTP concentration above saturating levels of UTP demonstrating that the order of addition of substrates is UTP followed by ATP and then NH3.

Adenosine Triphosphatases↗