Rendimiento diagnóstico de diferentes protocolos de estrés cardiaco usados en imagen de perfusión miocárdica para el diagnóstico de enfermedad coronaria usando una cámara de cadmio-zinc-telurio con correlación con angiografía coronaria / Diagnostic performance of different cardiac stress protocols for myocardial perfusion imaging for the diagnosis of coronary artery disease using a cadmium-zinc-telluride camera with invasive coronary angiography correlation

Objetivo Evaluar el rendimiento diagnóstico de tres protocolos diferentes de estrés cardiaco utilizados en imagen de perfusión miocárdica (IPM), usando una cámara de cadmio-zinc-telurio (CZT) en correlación con angiografía coronaria (AC) para el diagnóstico de enfermedad arterial coronaria (EAC) en una población de alto riesgo. Métodos Estudio retrospectivo realizado en 263 pacientes (96 mujeres y 167 varones, edad media 68 años), de los cuales 119 realizaron una prueba de estrés con bicicleta (PEB), 113 una prueba de estrés farmacológica (PEF) y 31 una combinación de ambas (PEC), entre septiembre de 2014 y diciembre de 2018. Posteriormente realizaron una IPM, seguida de AC dentro de los seis meses posteriores a la IPM. La probabilidad preprueba media para EAC según los criterios de la Sociedad Europea de Cardiología fue de 36%. La IPM se realizó en una cámara CZT cardio dedicada (D-SPECT Spectrum Dynamics) con un protocolo de dos días, de acuerdo con las guías de la Asociación Europea de Medicina Nuclear (EANM). Resultados No se observaron diferencias significativas entre los diferentes protocolos de estrés en términos de precisión diagnóstica (PEB 85%, PEF 88%, PEC 84%). La exactitud diagnóstica general de IPM para identificar pacientes con cualquier EAC obstructiva en AC fue de 86%, sensibilidad de 93%, especificidad de 54%, VPP de 90% y VPN de 63%. Conclusión La cámara CZT D-SPECT logra resultados generales satisfactorios en el diagnóstico de la EAC, sin encontrar diferencias significativas en el rendimiento diagnóstico cuando la prueba de esfuerzo se realizó como PEB, PEF o PEC. (AU)

Purpose To evaluate the diagnostic performance of three different cardiac stress protocols for myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) camera with invasive coronary angiography (ICA) correlation for the diagnosis of coronary artery disease in a high risk population. Methods Retrospective study of 263 patients (96 women and 167 males, mean age 68 years) from which 119 patients performed a bicycle stress test (BST), 113 pharmacological stress test (PST) and 31 a combination of the two (CST) between September 2014 and December 2018. The patients then underwent myocardial perfusion imaging (MPI), followed by ICA and evaluated by means of quantitative angiography software, within six months after the MPI. The mean pre-test probability score for coronary disease according to the European Society of Cardiology criteria was 36% for the whole population. The MPI was performed in a dedicated CZT cardio camera (D-SPECT Spectrum Dynamics) with a two-day protocol, according to the European Association of Nuclear Medicine guidelines. Results No significant difference was observed between the three stress protocols in terms of diagnostic accuracy (BST 85%, PST 88% and CST 84%). The overall diagnostic accuracy of MPI to identify patients with any obstructive CAD at ICA was 86%, Sensitivity 93%, Specificity 54%, PPV 90% and NPV 63%. Conclusion The CZT D-SPECT camera achieves overall satisfactory results in the diagnosis of CAD, observing no significant differences in the diagnostic performance when the stress test was performed as a BST, PST or CST (AU)

Inclusion of a GaAs detector model in the Photon Counting Toolkit software for the study of breast imaging systems.

We present an upgraded version of the Photon Counting Toolkit (PcTK), a freely available by request MATLAB tool for the simulation of semiconductor-based photon counting detectors (PCD), which has been extended and validated to account for gallium arsenide (GaAs)-based PCD(s). The modified PcTK version was validated by performing simulations and acquiring experimental data for three different cases. The LAMBDA 60 K module planar detector (X-Spectrum GmbH, Germany) based on the Medipix3 ASIC technology was used in all cases. This detector has a 500-µm thick GaAs sensor and a 256 × 256-pixel array with 55 µm pixel size. The first validation was a comparison between simulated and measured spectra from a 109Cd radionuclide source. In the second validation study, experimental measurements and simulations of mammography spectra were generated to observe the performance of the GaAs version of the PcTK with polychromatic radiation used in conventional x-ray imaging systems. The third validation study used single event analysis to validate the spatio-energetic model of the extended PcTK version. Overall, the software provided a good agreement between simulated and experimental data, validating the accuracy of the GaAs model. The software could be an attractive tool for accurate simulation of breast imaging modalities relying on photon counting detectors and therefore could assist in their characterization and optimization.

Formation of 107Cd radionuclide impurities during 18F production.

Cd isotopes (107Cd and 109Cd) are generated from the silver target body during the bombardment of [18O]water in the routine production of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) for PET (Positron Emission Tomography) diagnosis. Cadmium isotopes contribute significantly to the total activity of generated impurities and, due to being potentially radiotoxic to living organisms, they should be effectively reduced from FDG to prevent accidental injection of even small concentrations into patients. Purification of the final [18F]FDG can be based on a set of columns, fulfilling various functions in the cleaning process. To assess cadmium impurities and the efficiency of the purification process, a low background gamma spectrometry system with high resolution has been applied. Even activity of 3.5 kBq and 290 kBq has been measured on QMA (Sep-Pak Light Accell Plus QMA) columns for 109Cd and 107Cd isotopes, respectively. 107Cd activity in the five column set was higher than that of 109Cd. The rate of 18F production process was about 1 GBq/min, while that of 107Cd and 109Cd radionuclides was about 4.2 kBq/min and 50 Bq/min respectively. The same purification efficiency of both isotopes has been obtained at each step of the process. The production rate of 107Cd and 109Cd radionuclides was insignificant compared to the 18F production rate. Therefore [18F]FDG final product for use in injections before PET diagnostics was efficiently purified from cadmium radionuclide impurities.

Using isotopes to trace freshly applied cadmium through mineral phosphorus fertilization in soil-fertilizer-plant systems.

Applications of mineral phosphorus (P) fertilizer can lead to cadmium (Cd) accumulation in soils and can increase Cd concentrations in edible crop parts. To determine the fate of freshly applied Cd, a Cd source tracing experiment was conducted in three soil-fertilizer-wheat systems by using a mineral P fertilizer labeled with the radio isotope 109Cd and by exploiting natural differences in Cd stable isotope compositions (δ114/110Cd). Source tracing with stable isotopes overestimated the proportion of Cd in plants derived from the P fertilizer, because the isotope ratios of the sources were not sufficiently distinct from those of the soils. Despite indistinguishable extractable Cd pools between control and treatments, the addition of P fertilizer resulted in a more negative apparent isotope fractionation between soil and wheat. Overall, the radio isotope approach provided more robust results and revealed that 6.5 to 15% of the Cd in the shoot derived from the fertilizer. From the introduced Cd, a maximum of 2.2% reached the wheat shoots, whilst 97.8% remained in the roots and soils. The low recoveries of the fertilizer derived Cd suggest that continuous P fertilizer application in the past decades can lead to a build-up of a residual Cd pool in soils.

Dietary metal bioavailability in razor clam Sinonovacula constricta under fluctuating seston environments.

To understand the potential risks of dietary metals to marine bivalves, it is important to study the interaction between dietary metal bioaccumulation and bivalve feeding behavior. Key processes in affecting the dietary metal influx are the selection of different particles during the ingestion process as well as the differential assimilation of metals during the digestion process. In this study, we quantified the influences of seston quality and quantity on the dietary assimilation of Cd and Zn as well as pre-ingestion particle selectivity in a razor clam Sinonovacula constricta following feeding on radiolabeled diatoms and sediments with different mixtures at four food concentrations. Bioavailability of 109Cd and 65Zn from seston was measured by assimilation efficiency (AE) using a pulse-chase feeding technique. The AEs of Cd and Zn were significantly affected by the seston quantity and quality (higher for Zn than they were for Cd and higher for diatoms than for suspended sediments), but were independent of the presence of other particles during the feeding process. Dual gamma radiotracer technique was further employed to study pre-ingestion particle selectivity. Particle selectivity was weak during pre-ingestion in razor clams, although there was evidence that clams might be able to differentiate particles during the process of pseudofeces production. Our study demonstrated that seston composition and quantity substantially affected the bioavailability of Cd and Zn to the razor clams. The results are important to understand the bioaccumulation of metals in clams living in dynamic food environments of estuary.

Effects of ocean acidification on 109Cd, 57Co, and 134Cs bioconcentration by the European oyster (Ostrea edulis): Biokinetics and tissue-to-subcellular partitioning.

The uptake and depuration kinetics of dissolved 109Cd, 57Co and 134Cs were determined experimentally in the European flat oyster Ostrea edulis (Linnaeus, 1758) under different pH conditions (i.e., 8.1, 7.8 and 7.5) for 59 days. Uptake and depuration rates were variable within these elements; no effects were observed under different pH conditions for the uptake biokinetics of 109Cd and 57Co and depuration of 109Cd and 134Cs in oyster. The uptake and depuration rate constants of 134Cs differed during the exposure phase between treatments, while the steady state concentration factors (CFss) were similar. The resulting Cs activity that was purged during short- and long-term depuration phases differed, while the remaining activities after thirty-nine days depuration phase (RA39d) were similar. Co-57 depuration was affected by pCO2 conditions: RA39d were found to be significantly higher in oysters reared in normocapnia (pCO2 = 350 µatm) compared to high pCO2 conditions. Co-57 tissue distribution did not differ among the variable pCO2 conditions, while 109Cd and 134Cs accumulated in soft tissue of oysters were found to be higher under the highest pCO2. Additionally, Cd, Co and Cs were stored differently in various compartments of the oyster cells, i.e. cellular debris, metal-rich granules (MRG) and metallothionein-like proteins (MTLP), respectively. The subcellular sequestration of the elements at the end of the depuration phase did not differ among pH treatments. These results suggest that bioconcentration and tissue/subcellular distribution are element-specific in the oyster, and the effects of higher pCO2 driven acidification and/or coastal acidification variably influence these processes.

Comparing single-feeding and multi-feeding approaches for experimentally assessing trophic transfer of metals in fish.

Diet is an important pathway for metal uptake in marine organisms, and assimilation efficiency is one of the most relevant parameters to quantify trophic transfer of metals along aquatic food webs. The most commonly used method to estimate this parameter is pulse-chase feeding using radiolabeled food. This approach is, however, based on several assumptions that are not always tested in an experimental context. The present study aimed to validate the approach by assessing single-feeding and multiple-feeding approaches, using a model species (the turbot Scophthalmus maximus). Using the kinetic data obtained from the single-feeding experiment, the reconstruction of a multi-feeding experiment was tested for consistency with data provided by an actual multi-feeding performed under the same experimental conditions. The results validated the single-feeding approach. Environ Toxicol Chem 2017;36:1227-1234. © 2016 SETAC.

Cadmium-109 Radioisotope Adsorption onto Polypyrrole Coated Sawdust of Dryobalanops aromatic: Kinetics and Adsorption Isotherms Modelling.

A radiotracer study was conducted to investigate the removal characteristics of cadmium (109Cd) from aqueous solution by polypyrrole/ sawdust composite. Several factors such as solution pH, sorbent dosage, initial concentration, contact time, temperature and interfering metal ions were found to have influence on the adsorption process. The kinetics of adsorption was relatively fast, reaching equilibrium within 3 hours. A lowering of the solution pH reduced the removal efficiency from 99.3 to ~ 46.7% and an ambient temperature of 25°C was found to be optimum for maximum adsorption. The presence of sodium and potassium ions inhibited 109Cd removal from its aqueous solution. The experimental data for 109Cd adsorption showed a very good agreement with the Langmuir isotherm and a pseudo-first order kinetic model. The surface condition of the adsorbent before and after cadmium loading was investigated using BET, FESEM and FTIR. Considering the low cost of the precursor's materials and the toxicity of 109Cd radioactive metal, polypyrrole synthesized on the sawdust of Dryobalanops aromatic could be used as an efficient adsorbent for the removal of 109Cd radioisotope from radionuclide-containing effluents.

A feasibility study to determine the potential of in vivo detection of gadolinium by x-ray fluorescence (XRF) following gadolinium-based contrast-enhanced MRI.

The feasibility of using a (109)Cd γ-ray induced K x-ray fluorescence (K-XRF) system for the in vivo detection of gadolinium (Gd) in bone has been investigated. The K-XRF bone measurement system employs an array of four detectors, and is normally used for the non-invasive study of bone lead levels. The system was used to measure bone simulating phantoms doped with varying levels of gadolinium and fixed amounts of sodium (Na), chlorine (Cl) and calcium (Ca). The detection limits for bare bone phantoms, using a source of activity 0.17 GBq, were determined to be 3.9 ppm and 6.5 ppm (µg Gd per gram phantom) for the Kα1 and Kα2 Gd x-ray peaks, respectively. This leads to an overall detection limit of 3.3 ppm (µg Gd per gram phantom). Layers of plastic were used to simulate overlying soft tissue and this permitted prediction of a detection limit, using the current strength of our radioisotope source, of 6.1 ppm to 8.6 ppm (µg Gd per gram phantom) for fingers with 2-4 mm of overlying tissue. With a new source of activity 5 GBq, we predict that this system could achieve a detection limit of 4-5.6 µg Gd g(-1) Ca. This is within the range of levels (2-30 µg Gd g(-1) Ca) previously found in the bone of patients receiving Gd based contrast imaging agents. The technique is promising and warrants further investigation.

Hyperfine local probe study of alkaline-earth manganites SrMnO3 and BaMnO3.

We report perturbed angular correlation measurements with (111m)Cd/(111)Cd and (111)In/(111)Cd probes, at the ISOLDE-CERN facility, in the manganite compounds BaMnO3, with the 6H and 15R polymorphs, and SrMnO3, with the 4H polymorph. The electric field gradient (EFG) is measured, and found approximately constant in a large temperature range for all the compounds. The EFG is also calculated from first principles with density functional theory, and compared with experimental results by considering diluted substitutional Cd impurities. Based on the results, we assign as sites for the probes the Ba (for BaMnO3-6H, 15R) and Sr (for SrMnO3-4H) sites, apart from fractions of undetermined origin in the case of BaMnO3-6H. We predict the hyperfine parameters in the recently synthesized multiferroic manganite Sr(0.5)Ba(0.5)MnO3, and its variation with the structure and electric polarization, which is found to be very small.

A microautoradiographic method for fresh-frozen sections to reveal the distribution of radionuclides at the cellular level in plants.

Microautoradiography (MAR) is a conventional imaging method based on the daguerreotype. The technique is used to visualize the distribution of radionuclide-labeled compounds within a tissue section. However, application of the classical MAR method to plant tissue sections is associated with several difficulties. In this study, we report an MAR method applicable to fresh-frozen plant sections. Our method had two features: (i) the sample was kept frozen from plant tissue collection to radioisotope detection, making it possible to fix solutes without solvent exchange; and (ii) 1.2 µm thick polyphenylene sulfide film was inserted between the fresh-frozen plant section and the photosensitive nuclear emulsion to separate the section from the emulsion before autoradiography was conducted, which significantly improved the quality of the section until microscopic detection, the quality of the MAR image and the success rate. Then, the passage of cadmium (Cd) through vegetative rice stem tissue after 24 h of (109)Cd absorption was described for the first time using the MAR method. MAR clearly revealed the distribution of (109)Cd at the tissue level with high resolution. The (109)Cd concentration in phloem cells was found to be particularly high, whereas the xylem cells contained only small amounts of (109)Cd. The MAR method was also applicable for detecting (109)Cd and [(33)P]phosphate in roots. The MAR method developed here is expected to provide distribution images for a variety of compounds and ions in plant tissue.

Selective uptake, distribution, and redistribution of (109)Cd, (57)Co, (65)Zn, (63)Ni, and (134)Cs via xylem and phloem in the heavy metal hyperaccumulator Solanum nigrum L.

The focus of this article was to explore the translocation of (109)Cd, (57)Co, (65)Zn, (63)Ni, and (134)Cs via xylem and phloem in the newly found hyperaccumulator Solanum nigrum L. Two experiments with the uptake via the roots and transport of (109)Cd, (57)Co, and (65)Zn labeled by roots, and the redistribution of (109)Cd, (65)Zn, (57)Co, (63)Ni, and (134)Cs using flap label in S. nigrum in a hydroponic culture with a standard nutrient solution were conducted. The results showed that (109)Cd added for 24 h to the nutrient medium of young plants was rapidly taken up, transferred to the shoot, and accumulated in the cotyledons and the oldest leaves but was not efficiently redistributed within the shoot afterward leading to a rather low content in the fruits. In contrast, (57)Co was more slowly taken up and released to the shoot, but afterward, this element was redistributed from older leaves to younger leaves and maturing fruits. (65)Zn was rapidly taken up and transferred to the shoot (mainly to the youngest leaves and not to the cotyledons). Afterward, this radionuclide was redistributed within the shoot to the youngest organs and finally accumulated in the maturing fruits. After flap labeling, all five heavy metals tested ((109)Cd, (57)Co, (65)Zn, (63)Ni, (134)Cs) were exported from the labeled leaf and redistributed within the plant. The accumulation in the fruits was most pronounced for (63)Ni and (65)Zn, while a relatively high percentage of (57)Co was finally found in the roots. (134)Cs was roughly in the middle of them. The transport of (109)Cd differed from that previously reported for wheat or lupin and might be important for the potential of S. nigrum to hyperaccumulate cadmium.

Evaluation of in vivo detection properties of 22Na, 65Zn, 86Rb, 109Cd and 137Cs in plant tissues using real-time radioisotope imaging system.

In plant research, radioisotope imaging provides useful information about physiological activities in various tissues and elemental transport between plant organs. To expand the usage of imaging techniques, a new system was developed to visualize beta particles, x-rays and gamma-rays emitted from plant bodies. This real-time radioisotope imaging system (RRIS) visualizes radioactivity after conversion into light with a CsI(Tl) scintillator plate. Herein, the RRIS detection properties of the gamma-ray emitters (22)Na, (65)Zn, (86)Rb, (109)Cd and (137)Cs were evaluated in comparison with those of radioluminography (RLG) using an imaging plate. The lower quantitative detection limit (Bq mm(-2)) during a 15 min period ranged from 0.1 to 4, depending on the nuclide, similar to that of RLG. When the quantitative ability to detect radiation from various Arabidopsis tissues was analyzed, the quantitative capability in silique and the thick internode tended to be low. In an EGS5 simulation, beta particles were the greatest contributors to RRIS imaging of (22)Na, (86)Rb and (137)Cs, and low-energy x-rays contributed significantly to (65)Zn and (109)Cd detection. Thus, both self-absorption and air space between the sample and scintillator surface could impair quantitative RRIS imaging. Despite these issues, RRIS is suggested for quantitative time-course measurements of radionuclide motion within plants.

Characterization of rapid intervascular transport of cadmium in rice stem by radioisotope imaging.

Participation of the intervascular transport system within the rice stem during cadmium (Cd) partitioning was investigated by characterizing (109)Cd behaviour in the shoot. In addition, (45)Ca, (32)P, and (35)S partitioning patterns were analysed for comparison with that of (109)Cd. Each tracer was applied to the seedling roots for 15 min, and the shoots were harvested either at 15 min (i.e. immediately after tracer application) or at 48 h. Distribution patterns of each element at 15 min were studied to identify the primary transport pathway before remobilization was initiated. (32)P was preferentially transported to completely expanded leaf blades having the highest transpiration rate. The newest leaf received minimal amounts of (32)P. In contrast, the amount of (35)S transported to the newest leaf was similar to that transported to the other mature leaf blades. Preferential movement towards the newest leaf was evident for (109)Cd and (45)Ca. These results directly indicate that elemental transport is differentially regulated in the vegetative stem as early as 15 min before the elements are transported to leaves. Cd behaviour in the stem was investigated in detail by obtaining serial section images from the bottom part of shoots after (109)Cd was applied to a single crown root. At 30 min, the maximum amount of (109)Cd was distributed in the peripheral cylinder of the longitudinal vascular bundles (PV) and, interestingly, some amount of (109)Cd was transported downwards along the PV. This transport manner of (109)Cd provides evidence that Cd can be loaded on the phloem at the stem immediately after Cd is transported from the root.

In situ analysis of cadmium uptake in four sections of the gastro-intestinal tract of rainbow trout (Oncorhynchus mykiss).

This study links results from past in vitro and in vivo experiments, by implementing an in situ experiment in order to determine the relative importance for cadmium (Cd) uptake of different sections of the gastro-intestinal tract (GIT) of rainbow trout. Transport of Cd from four sections of the GIT of adult rainbow trout (~220 g) was individually examined by infusing ligated sections of the GIT in live, free-swimming fish with 50 µM Cd spiked with radiolabelled (109)Cd (0.5 µCi ml(-1)). Fish were exposed for an 8-h period. The percentage of the total injected (109)Cd which was internalized from the different segments was only between ~0.1 and ~7%, indicating low uptake efficiency. The stomach is the most important GIT segment for Cd transport into the internal compartment of the animal, while the posterior intestine also plays a significant role. The majority of (109)Cd recovered at the end of the flux period was detected within gut material (ranging from 28 to 95%); the portion of Cd which was internalized was largely found in the carcass (32 to 60%). Distribution between the measured organs varied with uptake from the various GIT sections. Our results also confirm that the GIT acts as a protective barrier against Cd uptake from dietary exposure.

Standardization of 125I and 109Cd by the photon-photon coincidence method in PTKMR-BATAN.

A photon-photon coincidence system was constructed for the standardization of (125)I and (109)Cd in PTKMR-BATAN, Indonesia. Two NaI(Tl) detectors of 76 mm diameter × 6mm thickness with 0.5mm aluminum window were used, which were positioned approximately symmetrically to the source holder. The electronic chain was almost the same as for a 4πß-γ system. The CANBERRA Multiport II multi channel analyzer was used for energy calibration and a Philips type PM3092 oscilloscope for visualization of the pulses. A polyethylene plastic was used as the source substrate for the (125)I and (109)Cd samples. The activity of a (125)I solution was measured by the photon-photon coincidence and the efficiency extrapolation method (Schrader and Walz, 1987), whereas the activity of a (109)Cd solution was determined by a tracer method using (125)I (Schrader, 2006). The result of the (125)I activity showed good agreement with the result of measurements using a calibrated ionization chamber, and the result of (109)Cd also showed good agreement with the measurements result using a LEGe detector.

Real-time imaging and analysis of differences in cadmium dynamics in rice cultivars (Oryza sativa) using positron-emitting 107Cd tracer.

BACKGROUND: Rice is a major source of dietary intake of cadmium (Cd) for populations that consume rice as a staple food. Understanding how Cd is transported into grains through the whole plant body is necessary for reducing rice Cd concentrations to the lowest levels possible, to reduce the associated health risks. In this study, we have visualized and quantitatively analysed the real-time Cd dynamics from roots to grains in typical rice cultivars that differed in grain Cd concentrations. We used positron-emitting 107Cd tracer and an innovative imaging technique, the positron-emitting tracer imaging system (PETIS). In particular, a new method for direct and real-time visualization of the Cd uptake by the roots in the culture was first realized in this work. RESULTS: Imaging and quantitative analyses revealed the different patterns in time-varying curves of Cd amounts in the roots of rice cultivars tested. Three low-Cd accumulating cultivars (japonica type) showed rapid saturation curves, whereas three high-Cd accumulating cultivars (indica type) were characterized by curves with a peak within 30 min after 107Cd supplementation, and a subsequent steep decrease resulting in maintenance of lower Cd concentrations in their roots. This difference in Cd dynamics may be attributable to OsHMA3 transporter protein, which was recently shown to be involved in Cd storage in root vacuoles and not functional in the high-Cd accumulating cultivars. Moreover, the PETIS analyses revealed that the high-Cd accumulating cultivars were characterized by rapid and abundant Cd transfer to the shoots from the roots, a faster transport velocity of Cd to the panicles, and Cd accumulation at high levels in their panicles, passing through the nodal portions of the stems where the highest Cd intensities were observed. CONCLUSIONS: This is the first successful visualization and quantification of the differences in whole-body Cd transport from the roots to the grains of intact plants within rice cultivars that differ in grain Cd concentrations, by using PETIS, a real-time imaging method.

In vitro characterization of cadmium transport along the gastro-intestinal tract of freshwater rainbow trout (Oncorhynchus mykiss).

An in vitro gut sac technique was used to examine the mechanism(s) of cadmium (Cd) uptake along the gastro-intestinal tract (GIT) of rainbow trout (Oncorhynchus mykiss). The spatial distribution of Cd between three compartments (mucus-binding, mucosal epithelium, and transport into blood space) was determined using a modified Cortland saline containing 50µM Cd (as CdCl(2)) labeled with (109)Cd radiotracer. Taking into account total surface areas, the order of relative importance for total Cd uptake rate was: posterior intestine>anterior intestine>stomach>mid intestine. Cd transport was not inhibited by experimentally reducing fluid transport rates by manipulation of osmotic gradients using mannitol, but was sensitive to internal luminal pressure changes, suggesting a mechanosensitive pathway. Q(10) values (1, 11, and 19°C) indicated a facilitated transport of Cd in the anterior- and mid-intestine. The effects of 10mM Ca on the kinetics of Cd uptake suggest the presence of a common uptake pathway for Cd and Ca in the stomach, anterior-, and mid-intestine. Further evidence of a shared route of entry was found using three Ca channel blockers, lanthanum, verapamil, and nifedipine: both voltage-insensitive and voltage-sensitive Ca channels appear to be present in either some, or all portions of the GIT. Elevated Fe (500µM), Mg (50mM), and Zn (500µM) showed varying degrees of inhibition of Cd transport depending on the compartment and segment of the GIT. Overall it appears that there are multiple sites, and mechanisms, of Cd uptake along the GIT of rainbow trout.

Characterization of basolateral-to-apical transepithelial transport of cadmium in intestinal TC7 cell monolayers.

Cadmium (Cd) is a toxic metal with an extremely long half-life in humans. The intestinal absorption of Cd has been extensively studied but the role the intestinal epithelium may play in metal excretion has never been considered. The basolateral (BL)-to-apical (AP) transepithelial transport of Cd was characterized in TC7 human intestinal cells. Both AP and BL uptakes varied with days in culture, and BL uptake was twofold higher compared to AP in differentiated cultures. A 50% increase in the BL uptake of 0.5 µM (109)Cd was observed at pH 8.5 in a chloride but not nitrate medium, suggesting the involvement of a pH-sensitive mechanism of transport for chloro-complexes. Fe and Zn inhibited the BL uptake of Cd whereas complexation by albumin had no effect, but the stimulatory effect of pH 8.5 was lost in the presence of albumin. The BL uptake of [(3)H]-MPP(+) and (109)Cd were both inhibited by decynium22 without reciprocal inhibition. MRP2 and MDR1 mRNA levels increased as a function of days in culture. A 25 and 20% decrease in the cellular AP efflux of Cd was observed in the presence of verapamil and probenecid, respectively. In cells treated with BSO, which lowered by 26% the total cellular thiol content, the inhibitory effect of verapamil increased, whereas that of probenecid decreased. These results reveal the existence of a decynium22-sensitive mechanism of transport for Cd at the BL membrane, and suggest the involvement of MDR1 and MRP2 in cellular Cd efflux at the AP membrane. It is conceivable that the intestinal epithelium may contribute to Cd blood excretion.