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1.
Radiat Res ; 192(6): 649-661, 2019 12.
Article in English | MEDLINE | ID: mdl-31609677

ABSTRACT

Assessment of health effects from low-dose radiation exposures in patients undergoing diagnostic imaging is an active area of research. High-quality dosimetry information pertaining to these medical exposures is generally not readily available to clinicians or epidemiologists studying radiation-related health risks. The purpose of this study was to provide methods for organ dose estimation in pediatric patients undergoing four common diagnostic fluoroscopy procedures: the upper gastrointestinal (UGI) series, the lower gastrointestinal (LGI) series, the voiding cystourethrogram (VCUG) and the modified barium swallow (MBS). Abstracted X-ray film data and physician interviews were combined to generate procedure outlines detailing X-ray beam projections, imaged anatomy, length of X-ray exposure, and presence and amount of contrast within imaged anatomy. Monte Carlo radiation transport simulations were completed for each of the four diagnostic fluoroscopy procedures across the 162-member (87 males and 75 females) University of Florida/National Cancer Institute pediatric phantom library, which covers variations in both subject height and weight. Absorbed doses to 28 organs, including the active marrow and bone endosteum, were assigned for all 162 phantoms by procedure. Additionally, we provide dose coefficients (DCs) in a series of supplementary tables. The DCs give organ doses normalized to procedure-specific dose metrics, including: air kerma-area product (µGy/mGy · cm2), air kerma at the reference point (µGy/µGy), number of spot films (SF) (µGy/number of SFs) and total fluoroscopy time (µGy/s). Organs accumulating the highest absorbed doses per procedure were as follows: kidneys between 0.9-25.4 mGy, 1.1-16.6 mGy and 1.1-9.7 mGy for the UGI, LGI and VCUG procedures, respectively, and salivary glands between 0.2-3.7 mGy for the MBS procedure. Average values of detriment-weighted dose, a phantom-specific surrogate for the effective dose based on ICRP Publication 103 tissue-weighting factors, were 0.98 mSv, 1.16 mSv, 0.83 mSv and 0.15 mSv for the UGI, LGI, VCUG and MBS procedures, respectively. Scalable database of organ dose coefficients by patient sex, height and weight, and by procedure exposure time, reference point air kerma, kerma-area product or number of spot films, allows clinicians and researchers to compute organ absorbed doses based on their institution-specific and patient-specific dose metrics. In addition to informing on patient dosimetry, this work has the potential to facilitate exposure assessments in epidemiological studies designed to investigate radiation-related risks.


Subject(s)
Databases, Factual , Fluoroscopy/methods , Phantoms, Imaging , Radiation Dosage , Radiometry/methods , Adolescent , Adult , Barium/pharmacokinetics , Child , Computer Simulation , Female , Humans , Male , Monte Carlo Method , Radiography , Tissue Distribution
2.
Chemosphere ; 219: 836-844, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30572235

ABSTRACT

Macrophytes are widely used in water treatment and have potential for remediation of flooded soils. Many techniques have been proposed to increase the phytoextraction of metals by macrophytes, however, the knowledge of periods of maximum absorption and translocation is essential and is a gap in the management of phytoremediation. To evaluate the absorption and translocation of Ba over time by Eleocharis acutangula, a greenhouse experiment was conducted and the dry matter production of plants, Ba content in the roots and aerial parts, mass of Ba accumulated in plants, translocation factors and removal coefficients of Ba, and Ba content in two layers of the soil (0.0-0.1 m and 0.1-0.2 m) were determined. The highest translocation rates were observed after 105 days of cultivation, when the plants reached a state of hyperaccumulation. The maximum accumulation of barium occurred in the aerial parts of the plants at 105 days and in the roots at both 120 and 180 days. The barium content was reduced up to 120 days, as a result of an increase in available barium content in the soil layer of 0.0-0.1 m up to 105 days and in the layer 0.10-0.20 m up to 120 days, favoring the intense accumulation of Ba during this period. After 120 days of cultivation, the accumulation in the roots maintained a high coefficient of removal of Ba from the soil to the plant. After 180 days the available barium in the soil was depleted due to this high rate of removal by the roots.


Subject(s)
Barium/pharmacokinetics , Biodegradation, Environmental , Eleocharis/metabolism , Floods , Barium/analysis , Plant Roots/metabolism , Soil/chemistry , Soil Pollutants/analysis , Time Factors
3.
Environ Sci Pollut Res Int ; 24(34): 26634-26645, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28956246

ABSTRACT

The present study was designed to investigate the hematotoxicity, sero-biochemical and histological changes due to the accumulation of BaCl2 and BaCO3, the most important barium salts in our daily lives, in different soft tissues including the liver, kidney, heart, and spleen of adult rats after an oral exposure for 30 consecutive days, and to explain the different mechanisms by which this metal can exert these impacts. For this purpose, adult male rats were divided into three main groups of 15 animals each: group I, serving as controls, group II, receiving BaCl2 orally in a dose of 179 mg barium/kg b.wt, and group III, receiving BaCO3 orally in a dose of 418 mg barium/kg b.wt. for 30 consecutive days. Obviously, normocytic normochromic anemia was evident in both barium groups. Serum biochemical analysis revealed significant declines in glutathione peroxidase, catalase, superoxide dismutase, and urea with significant elevations in malondialdehyde, lactate dehydrogenase, and creatine kinase levels. Hyperphosphatemia, hypokalemia, hypocalcemia, and hypochloremia were also evident in both barium groups. Besides, residual analysis of both barium salts in different body organs revealed significantly abundant barium residues in the liver, spleen, heart, and kidney, respectively in both barium salts groups. Moreover, splenic tissue showed hemosiderosis, peritubular congestion, and necrotic glomeruli with intratubular hemorrhage. Sever subepicardial congestion with intramuscular edema was evident in the heart. In conclusion, BaCl2 and BaCO3 were able to deliver mortalities, antioxidant enzymes exhaustion, and a sort of normocytic normochromic anemia, as well as marked disturbances in cardiac, hepatic, and renal functions due to the accumulation of these two salts in the soft tissues. Therefore, these results demonstrate the unrecognized toxicity of those two barium salts due to their accumulation in various soft tissues of the body and so, this needs to reconsider about barium exposure.


Subject(s)
Anemia/chemically induced , Barium Compounds/toxicity , Barium/toxicity , Carbonates/toxicity , Chlorides/toxicity , Kidney/metabolism , Liver/metabolism , Myocardium/metabolism , Anemia/blood , Anemia/enzymology , Animals , Antioxidants/metabolism , Barium/pharmacokinetics , Barium Compounds/pharmacokinetics , Carbonates/pharmacokinetics , Chlorides/pharmacokinetics , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Male , Myocardium/pathology , Rats , Rats, Sprague-Dawley , Tissue Distribution
4.
PLoS One ; 12(7): e0180324, 2017.
Article in English | MEDLINE | ID: mdl-28683124

ABSTRACT

Current photon counting x-ray detector (PCD) technology faces limitations associated with spectral fidelity and photon starvation. One strategy for addressing these limitations is to supplement PCD data with high-resolution, low-noise data acquired with an energy-integrating detector (EID). In this work, we propose an iterative, hybrid reconstruction technique which combines the spectral properties of PCD data with the resolution and signal-to-noise characteristics of EID data. Our hybrid reconstruction technique is based on an algebraic model of data fidelity which substitutes the EID data into the data fidelity term associated with the PCD reconstruction, resulting in a joint reconstruction problem. Within the split Bregman framework, these data fidelity constraints are minimized subject to additional constraints on spectral rank and on joint intensity-gradient sparsity measured between the reconstructions of the EID and PCD data. Following a derivation of the proposed technique, we apply it to the reconstruction of a digital phantom which contains realistic concentrations of iodine, barium, and calcium encountered in small-animal micro-CT. The results of this experiment suggest reliable separation and detection of iodine at concentrations ≥ 5 mg/ml and barium at concentrations ≥ 10 mg/ml in 2-mm features for EID and PCD data reconstructed with inherent spatial resolutions of 176 µm and 254 µm, respectively (point spread function, FWHM). Furthermore, hybrid reconstruction is demonstrated to enhance spatial resolution within material decomposition results and to improve low-contrast detectability by as much as 2.6 times relative to reconstruction with PCD data only. The parameters of the simulation experiment are based on an in vivo micro-CT experiment conducted in a mouse model of soft-tissue sarcoma. Material decomposition results produced from this in vivo data demonstrate the feasibility of distinguishing two K-edge contrast agents with a spectral separation on the order of the energy resolution of the PCD hardware.


Subject(s)
Contrast Media/pharmacokinetics , Photons , Radiographic Image Interpretation, Computer-Assisted/methods , Sarcoma/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Animals , Barium/pharmacokinetics , Calcium/pharmacokinetics , Iodine/pharmacokinetics , Mice , Phantoms, Imaging , Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Tomography, X-Ray Computed/methods
5.
Chemosphere ; 144: 1421-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26495826

ABSTRACT

Barite contamination of soil commonly occurs from either barite mining or explorative drilling operations. This work reported in vitro data for barite contaminated soils using the physiologically based extraction test (PBET) methodology. The existence of barite in plant tissue and the possibility of 'biomineralised' zones was also investigated using Scanning Electron Microscopy. Soils with low barium (Ba) concentrations showed a higher proportion of Ba extractability than barite rich samples. Barium uptake to spinach from soil was different between short term spiking studies and field weathered soils. Furthermore, Ba crystals were not evident in spinach tissue or acid digest solutions grown in barium nitrate spiked soils despite high accumulation. Barite was found in the plant digest solutions from barite contaminated soils only. Results indicate that under the conservative assumptions made, a child would need to consume extreme quantities of soil over an extended period to cause chronic health problems.


Subject(s)
Barium Sulfate/pharmacokinetics , Barium/pharmacokinetics , Soil Pollutants/pharmacokinetics , Spinacia oleracea/metabolism , Biological Availability , Child , Child, Preschool , Humans , Risk Assessment , South Australia , Stomach/chemistry
6.
Environ Geochem Health ; 36(4): 797-814, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24844320

ABSTRACT

There is an increasing public awareness of the relatively new and expanded industrial barium uses which are potential sources of human exposure (e.g., a shale gas development that causes an increased awareness of environmental exposures to barium). However, absorption of barium in exposed humans and a full spectrum of its health effects, especially among chronically exposed to moderate and low doses of barium populations, remain unclear. We suggest a systematic literature review (from 1875 to 2014) on environmental distribution of barium, its bioaccumulation, and potential and proven health impacts (in animal models and humans) to provide the information that can be used for optimization of future experimental and epidemiological studies and developing of mitigative and preventive strategies to minimize negative health effects in exposed populations. The potential health effects of barium exposure are largely based on animal studies, while epidemiological data for humans, specifically for chronic low-level exposures, are sparse. The reported health effects include cardiovascular and kidney diseases, metabolic, neurological, and mental disorders. Age, race, dietary patterns, behavioral risks (e.g., smoking), use of medications (those that interfere with absorbed barium in human organism), and specific physiological status (e.g., pregnancy) can modify barium effects on human health. Identifying, evaluating, and predicting the health effects of chronic low-level and moderate-level barium exposures in humans is challenging: Future research is needed to develop an understanding of barium bioaccumulation in order to mitigate its potential health impacts in various exposured populations. Further, while occupationally exposed at-risk populations exist, it is also important to identify potentially vulnerable subgroups among non-occupationally exposed populations (e.g., elderly, pregnant women, children) who are at higher risk of barium exposure from drinking water and food.


Subject(s)
Barium/analysis , Barium/toxicity , Environmental Exposure/adverse effects , Administration, Oral , Animals , Barium/pharmacokinetics , Drinking Water , Environmental Exposure/analysis , Humans , Industry , Risk Assessment
7.
Environ Sci Technol ; 47(9): 4670-6, 2013 May 07.
Article in English | MEDLINE | ID: mdl-23484806

ABSTRACT

Barium (Ba) is a nonessential element to terrestrial organisms and is known to be toxic at elevated concentrations. In this study, the bioavailability and toxicity of Ba in barite (BaSO4) contaminated soils was studied using standard test organisms (Lactuca sativa L. "Great Lakes", Eisenia fetida). Contamination resulted from barite mining activities. Barium concentrations in contaminated soils determined by X-ray fluorescence were in the range 0.13-29.2%. Barite contaminated soils were shown to negatively impact both E. fetida and L. sativa relative to control soil. For E. fetida, pore-water concentrations and acid extractable Ba were linearly related to % body weight loss. In L. sativa, pore-water Ba and exchangeable Ba were both strongly related to shoot Ba and shoot biomass production. A negative linear relationship was observed between shoot Ba content and shoot weight (P < 0.0004, R(2) = 0.39), indicating that Ba accumulation is likely to have induced phytotoxicity. Plant weights were correlated to % weight loss in earthworm (r = -0.568, P = 0.028). Barium concentrations in pore-water were lower than predicted from barite solubility estimates but strongly related to exchangeable Ba, indicating an influence of ion exchange on Ba solubility and toxicity to E. fetida and L. sativa.


Subject(s)
Barium Sulfate/toxicity , Barium/pharmacokinetics , Invertebrates/metabolism , Plants/metabolism , Soil Pollutants/toxicity , Animals , Barium Sulfate/pharmacokinetics , Biological Availability , Humans , Oligochaeta , Soil Pollutants/pharmacokinetics
8.
J Agric Food Chem ; 60(38): 9543-52, 2012 Sep 26.
Article in English | MEDLINE | ID: mdl-22950648

ABSTRACT

Two field experiments were conducted to investigate the effects of previous cultivation of an arbuscular mycorrhizal (AM) host plant and manure application on the concentration of 19 mineral elements in soybean ( Glycine max L. Merr. cv. Tsurumusume) seeds. Each experiment ran for two years (experiment 1 took place in 2007-2008, and experiment 2 took place in 2008-2009) with a split plot design. Soybeans were cultivated after growing either an AM host plant (maize, Zea mays L. cv. New dental) or a non-AM host plant (buckwheat, Fagopyrum esculentum Moench. cv. Kitawase-soba) in the first year in the main plots, with manure application (0 and 20 t/ha) during the soybean season in split plots from both main plots. On the basis of the two experiments, manure application significantly increased the available potassium (K) and decreased the available iron (Fe) and cesium (Cs) in the soil. However, higher concentrations of cadmium (Cd) and barium (Ba) and lower concentrations of Cs in the seed were induced by the application of manure. Cd levels in the seed were decreased by prior cultivation with the AM host plant. The present study showed that the identity of the prior crop and manure application changed the mineral contents of the soybean seed and suggests a connection between environmental factors and food safety.


Subject(s)
Glycine max/physiology , Manure , Mycorrhizae , Seeds/chemistry , Barium/pharmacokinetics , Cadmium/pharmacokinetics , Calcium/pharmacokinetics , Cesium/pharmacokinetics , Crops, Agricultural , Fagopyrum , Fertilizers , Iron/pharmacokinetics , Potassium/pharmacokinetics , Seeds/metabolism , Soil , Glycine max/microbiology , Zea mays
9.
Neurotoxicology ; 33(5): 1276-83, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22884792

ABSTRACT

PURPOSE: We continuously ingest barium as a general element by drinking water and foods in our daily life. Exposure to high-dose barium (>100mg/kg/day) has been shown to cause physiological impairments. Direct administration of barium to inner ears by vascular perfusion has been shown to cause physiological impairments in inner ears. However, the toxic influence of oral exposure to low-dose barium on hearing levels has not been clarified in vivo. We analyzed the toxic influence of oral exposure to low-dose barium on hearing levels and inner ears in mice. EXPERIMENTAL DESIGN: We orally administered barium at low doses of 0.14 and 1.4 mg/kg/day to wild-type ICR mice by drinking water. The doses are equivalent to and 10-fold higher than the limit level (0.7 mg/l) of WHO health-based guidelines for drinking water, respectively. After 2-week exposure, hearing levels were measured by auditory brain stem responses and inner ears were morphologically analyzed. After 2-month exposure, tissue distribution of barium was measured by inductively coupled plasma mass spectrometry. RESULTS: Low-dose barium in drinking water caused severe hearing loss in mice. Inner ears including inner and outer hair cells, stria vascularis and spiral ganglion neurons showed severe degeneration. The Barium-administered group showed significantly higher levels of barium in inner ears than those in the control group, while barium levels in bone did not show a significant difference between the two groups. Barium levels in other tissues including the cerebrum, cerebellum, heart, liver and kidney were undetectably low in both groups. CONCLUSIONS: Our results demonstrate for the first time that low-dose barium administered by drinking water specifically distributes to inner ears resulting in severe ototoxicity with degeneration of inner ears in mice.


Subject(s)
Barium/administration & dosage , Hearing Loss/chemically induced , Water Pollutants, Chemical/administration & dosage , Acoustic Stimulation , Acoustics , Animals , Barium/pharmacokinetics , Brain/drug effects , Brain/metabolism , Brain/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Evoked Potentials, Auditory, Brain Stem/drug effects , Female , Kidney/metabolism , Kidney/pathology , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred ICR , Microscopy, Electron, Transmission , Myocardium/metabolism , Myocardium/pathology , Neurons/pathology , Neurons/ultrastructure , Spectrophotometry, Atomic/methods , Spiral Ganglion/pathology , Time Factors , Tissue Distribution/drug effects , Water Pollutants, Chemical/pharmacokinetics
10.
Int J Pharm ; 431(1-2): 90-100, 2012 Jul 15.
Article in English | MEDLINE | ID: mdl-22546295

ABSTRACT

Gastric retention is postulated as an approach to improve bioavailability of compounds with narrow absorption windows. To elucidate the role of image size on gastric retention and pharmacokinetics, formulations with different image sizes and swelling kinetics but similar dissolution rates were designed and imaged in dogs. Diet had a clear effect, with increasing calorific intake prolonging retention in the dog model. In contrast to clinical observations, no obvious effect of image size on gastric retention was observed in the dog, with the larger gastric retentive (GR) and smaller controlled release (CR) formulations both demonstrating similar gastric emptying. Comparable pharmacokinetic profiles were observed for the two formulations, corroborating the imaging data and providing evidence of similar in vivo dissolution rates and dosage form integrity in the dog. Food, specifically meal composition, resulted in comparable enhancements in exposure in the dog and clinic due to prolonged gastric retention. However, differentiating retention based on image size in the dog was not feasible due to the smaller pyloric aperture compared to humans. This work illustrates that the dog is capable of determining the pharmacokinetic advantage of gastric retention relative to immediate release (IR) or CR formulations, however, has limited value in differentiating between CR and GR formulations.


Subject(s)
Gastric Emptying , Metformin/pharmacokinetics , Animals , Barium/pharmacokinetics , Biological Availability , Cellulose/chemistry , Cellulose/pharmacokinetics , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Diagnostic Imaging , Dogs , Drug Compounding , Energy Intake , Fasting , Food-Drug Interactions , Hypromellose Derivatives , Lactose/chemistry , Lactose/pharmacokinetics , Male , Metformin/blood , Metformin/chemistry , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Methylcellulose/pharmacokinetics , Solubility , Stearic Acids/chemistry , Stearic Acids/pharmacokinetics
11.
J Med Primatol ; 40(3): 181-7, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21320131

ABSTRACT

BACKGROUND: Lengthy social separation and prolonged fasting time contribute to increased risks associated with anesthesia in captive primates. This study is an initial attempt to identify a safe pre-anesthetic fasting procedure by identifying gastric emptying time (GET) and gastrointestinal transit time (GTT) of captive chimpanzees, Pan troglodytes. METHODS: Seven adult chimpanzees at the North Carolina Zoo immobilized for annual physical examinations were fed barium-impregnated polyethylene spheres to measure GET. Eleven animals were individually fed a color dye marker and fecal passage was observed to determine GTT. RESULTS: Gastric emptying time (GET) was approximated to be >3 hours but <16 hours. The mean GTT was 16.5 hours. CONCLUSIONS: This study indicates that a fasting time of 3 hours would allow for complete gastric emptying and could potentially replace the current overnight fast (≥16 hour) to help minimize complications associated with pre-anesthetic fasting in captive primates.


Subject(s)
Anesthesia/veterinary , Fasting , Gastric Emptying , Gastrointestinal Transit , Pan troglodytes/physiology , Veterinary Medicine/methods , Animals , Barium/administration & dosage , Barium/pharmacokinetics , Coloring Agents/administration & dosage , Coloring Agents/pharmacokinetics , Female , Gastrointestinal Tract/diagnostic imaging , Gastrointestinal Tract/physiology , Male , Polyethylene/administration & dosage , Polyethylene/pharmacokinetics , Radiography , Time Factors
12.
J Hazard Mater ; 181(1-3): 1148-57, 2010 Sep 15.
Article in English | MEDLINE | ID: mdl-20579810

ABSTRACT

A long-term experiment was carried out under field conditions in Jaboticabal, SP, Brazil, with the objective of evaluating the concentration of Ba in soil and in maize plants grown in a soil treated with sewage sludge for nine consecutive years. During 2005/2006, maize was used as test plants and the experimental design was in randomized complete blocks with four treatments and five replicates. Treatments consisted of: 0.0, 45.0, 90.0 and 127.5 t ha(-1) sewage sludge (dry basis). Sewage sludge application increased soil Ba concentration. Barium accumulated in the parts of maize plants were generally affected by the successive applications of sewage sludge to the soil. However, the concentration of Ba in maize grain did not exceed the critical levels of Ba for human consumption. Sewage sludge applied to soil for a long time did not affect dry matter and grain production, nevertheless had the similar effect of mineral fertilization.


Subject(s)
Barium/pharmacokinetics , Sewage/chemistry , Zea mays/metabolism , Biodegradation, Environmental , Fertilizers , Humans , Longitudinal Studies , Soil Pollutants/analysis
13.
Am J Physiol Renal Physiol ; 296(5): F966-75, 2009 May.
Article in English | MEDLINE | ID: mdl-19297448

ABSTRACT

The cortical collecting duct (CCD) plays a key role in regulated K(+) secretion, which is mediated mainly through renal outer medullary K(+) (ROMK) channels located in the apical membrane. However, the mechanisms of the regulation of urinary K(+) excretion with regard to K(+) balance are not well known. We took advantage of a recently established mouse CCD cell line (mCCD(cl1)) to investigate the regulation of K(+) secretion by mineralocorticoid and K(+) concentration. We show that this cell line expresses ROMK mRNA and a barium-sensitive K(+) conductance in its apical membrane. As this conductance is sensitive to tertiapin-Q, with an apparent affinity of 6 nM, and to intracellular acidification, it is probably mediated by ROMK. Overnight exposure to 100 nM aldosterone did not significantly change the K(+) conductance, while it increased the amiloride-sensitive Na(+) transport. Overnight exposure to a high K(+) (7 mM) concentration produced a small but significant increase in the apical membrane barium-sensitive K(+) conductance. The mRNA levels of all ROMK isoforms measured by qRT-PCR were not changed by altering the basolateral K(+) concentration but were decreased by 15-45% upon treatment with aldosterone (0.3 or 300 nM for 1 and 3 h). The paradoxical response of ROMK expression to aldosterone could possibly work as a preventative mechanism to avoid excessive K(+) loss which would otherwise result from the increased electrogenic Na(+) transport and associated depolarization of the apical membrane in the CCD. In conclusion, mCCD(cl1) cells demonstrate a significant K(+) secretion, probably mediated by ROMK, which is not stimulated by aldosterone but increased by overnight exposure to a high K(+) concentration.


Subject(s)
Kidney Tubules, Collecting/cytology , Kidney Tubules, Collecting/physiology , Mineralocorticoids/metabolism , Potassium Channels, Inwardly Rectifying/genetics , Potassium/pharmacokinetics , Amino Acid Sequence , Animals , Barium/pharmacokinetics , Bee Venoms/pharmacology , Cell Line , Cell Polarity/physiology , Culture Media/pharmacology , Dose-Response Relationship, Drug , Gene Expression/drug effects , Gene Expression/physiology , Isomerism , Kidney Cortex/cytology , Kidney Cortex/physiology , Mice , Molecular Sequence Data , Potassium Channels, Inwardly Rectifying/chemistry , Potassium Channels, Inwardly Rectifying/metabolism , RNA, Messenger/metabolism
14.
Pflugers Arch ; 455(5): 913-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17909852

ABSTRACT

The recently reported alpha1D Ca channel in the heart is known to be regulated by protein kinase C (PKC) at the whole cell level and has been implicated in atrial fibrillation. The biophysical basis of this regulation at the single-channel level is not known. Therefore, the effect of PKC activation was studied on alpha1D Ca channel expressed in tsA201 cells using cell-attached configuration. Unitary currents were recorded in the presence of 70 mM Ba2+ as the charge carrier at room temperature. Under basal condition, channel activity was rare and infrequent; however, Bay K 8644 (1 microM) induced channel openings with a conductance of 22.3 pS. Single channel analysis of open and closed time distributions were best fitted with a single exponential. PKC activation by 4alpha-phorbol 12-myristate 13-acetate (PMA; 10 nM), a phorbol ester derivative, resulted in a decrease in open probability and increase in closed-time without any significant effect on the conductance of the alpha1D Ca channel. This is consistent with a decreased entry of alpha1D Ca channel into open states in the presence of PMA. PMA effects could not be reproduced by 4-alpha Phorbol, an inactive PMA analogue. These data show, for the first time, (1) the alpha1D Ca channel activity at the single-channel level and (2) the biophysical basis by which PKC activation inhibits the alpha1D Ca channel. The shortening of the open-time and the lengthening of the closed-time constants and the increase in blank sweeps may explain the inhibition of the previously reported whole-cell alpha1D Ca current. Altogether, these data are essential for understanding the complex role of alpha1D Ca channel not only in physiological settings but also in pathological settings such as atrial fibrillation.


Subject(s)
Atrial Fibrillation/physiopathology , Calcium Channels, L-Type/physiology , Ion Channel Gating/physiology , Protein Kinase C/metabolism , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology , Animals , Atrial Fibrillation/metabolism , Barium/pharmacokinetics , Calcium Channel Agonists/pharmacology , Carcinogens/pharmacology , Cell Line , Enzyme Activation/drug effects , Enzyme Activation/physiology , Humans , Ion Channel Gating/drug effects , Kidney/cytology , Kinetics , Patch-Clamp Techniques , Rats , Tetradecanoylphorbol Acetate/pharmacology
15.
Cell Mol Neurobiol ; 27(7): 901-8, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17934806

ABSTRACT

(1) Voltage-gated Ca2+ (CaV) channels are multi-subunit membrane complexes that allow depolarization-induced Ca2+ influx into cells. The skeletal muscle L-type CaV channels consist of an ion-conducting CaV1.1 subunit and auxiliary alpha2delta-1, beta1 and gamma1 subunits. This complex serves both as a CaV channel and as a voltage sensor for excitation-contraction coupling. (2) Though much is known about the mechanisms by which the alpha2delta-1 and beta1 subunits regulate CaV channel function, there is far less information on the gamma1 subunit. Previously, we characterized the interaction of gamma1 with the other components of the skeletal CaV channel complex, and showed that heterologous expression of this auxiliary subunit decreases Ca2+ current density in myotubes from gamma1 null mice. (3) In the current report, using Western blotting we show that the expression of the CaV1.1 protein is significantly lower when it is heterologously co-expressed with gamma1. Consistent with this, patch-clamp recordings showed that transient transfection of gamma1 drastically inhibited macroscopic currents through recombinant N-type (CaV2.2/alpha2delta-1/beta3) channels expressed in HEK-293 cells. (4) These findings provide evidence that co-expression of the auxiliary gamma1 subunit results in a decreased expression of the ion-conducting subunit, which may help to explain the reduction in Ca2+ current density following gamma1 transfection.


Subject(s)
Calcium Channels, L-Type/genetics , Calcium Channels, L-Type/metabolism , Muscle, Skeletal/physiology , Protein Subunits/genetics , Protein Subunits/metabolism , Animals , Barium/pharmacokinetics , Cell Line , Down-Regulation/physiology , Humans , Kidney/cytology , Patch-Clamp Techniques , Rabbits , Transfection
16.
Environ Sci Technol ; 41(13): 4813-20, 2007 Jul 01.
Article in English | MEDLINE | ID: mdl-17695934

ABSTRACT

Barium is a heavy metal to which human and animal receptors may be exposed in various settings--for example, in mineral extraction industries where the mining and milling of ores occurs. Aluminum is also an element abundant in soil and dust to which human and animal receptors may be exposed in association with such industries. This study investigated the solubility and bioaccessibility of barium and aluminum in simulated gastric fluids using an in vitro test method previously validated for lead. Soil samples were collected from the vicinity of a mine and transport road that generated fugitive dust containing barium as barite (BaSO4). It was found that barium bioaccessibility in different tundra soil and fugitive dust source materials varied greatly, between 0.07 and 66.0%, depending on sample location, grain size, solid-to-fluid ratio used in the in vitro experiments, and the analytical method selected for determining total barium concentrations in the sample substrates. For X-ray fluorescence spectrometry (XRF) analytical methods and a solid-to-fluid ratio of 1:100, barium bioaccessibility from the barite-rich mine waste rock and gyro crusher ore dust source materials was very low (0.07-0.36%). By contrast, the bioaccessibility of barium in tundra soil samples affected by fugitive dust deposition ranged from 3.8 to 19.5%. The relative solubility of barium measured in the simulated gastric fluids of this study is consistent with time-dependent dissolution of barite in mine waste rock and ore dust, and the presence of more soluble chemical forms in tundra soil. Laboratory XRF analysis was the only analytical method used in this study that accurately characterized total barium concentrations for all sample substrates. Aluminum bioaccessibility was distinguished from barium bioaccessibility by its generally lower values and smaller dependence on grain size and solid-to-fluid ratios. The range of aluminum bioaccessibility values (0.31-4.0%) is consistent with the predominance of aluminum in relatively insoluble aluminosilicate minerals.


Subject(s)
Aluminum/chemistry , Barium/chemistry , Dust , Mining , Aluminum/pharmacokinetics , Barium/pharmacokinetics , Biological Availability , Solubility , Spectrometry, Fluorescence/methods
17.
AJR Am J Roentgenol ; 189(2): W56-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17646438

ABSTRACT

OBJECTIVE: The objective of our study was to evaluate the feasibility and efficacy of a radiologic technique in increasing colon visibility in colonic transit time studies. Three radiologists counted segmental colonic radiopaque markers in two patient groups, based on classic criteria in the first group and also on a colonic barium trace in the second. Agreement between marker counts was assessed using method comparison analysis. CONCLUSION: With the barium trace technique, the anatomic conspicuity of colonic segments is improved, a correct segmental marker count can be obtained, and colonic inertia can be more easily distinguished from distal constipation.


Subject(s)
Colon/diagnostic imaging , Colon/physiopathology , Constipation/diagnostic imaging , Constipation/physiopathology , Gastrointestinal Transit , Radiography, Abdominal , Adult , Aged , Aged, 80 and over , Analysis of Variance , Barium/pharmacokinetics , Contrast Media/pharmacokinetics , Feasibility Studies , Female , Humans , Male , Middle Aged , Reproducibility of Results , Time Factors
18.
J Neurosci ; 25(30): 7071-80, 2005 Jul 27.
Article in English | MEDLINE | ID: mdl-16049184

ABSTRACT

P/Q-type Ca2+ currents through presynaptic CaV2.1 channels initiate neurotransmitter release, and differential modulation of these channels by neuronal calcium-binding proteins (nCaBPs) may contribute to synaptic plasticity. The nCaBPs calcium-binding protein 1 (CaBP1) and visinin-like protein-2 (VILIP-2) differ from calmodulin (CaM) in that they have an N-terminal myristoyl moiety and one EF-hand that is inactive in binding Ca2+. To determine whether myristoylation contributes to their distinctive modulatory properties, we studied the regulation of CaV2.1 channels by the myristoyl-deficient mutants CaBP1/G2A and VILIP-2/G2A. CaBP1 positively shifts the voltage dependence of CaV2.1 activation, accelerates inactivation, and prevents paired-pulse facilitation in a Ca2+-independent manner. Block of myristoylation abolished these effects, leaving regulation that is similar to endogenous CaM. CaBP1/G2A binds to CaV2.1 with reduced stability, but in situ protein cross-linking and immunocytochemical studies revealed that it binds CaV2.1 in situ and is localized to the plasma membrane by coexpression with CaV2.1, indicating that it binds effectively in intact cells. In contrast to CaBP1, coexpression of VILIP-2 slows inactivation in a Ca2+-independent manner, but this effect also requires myristoylation. These results suggest a model in which nonmyristoylated CaBP1 and VILIP-2 bind to CaV2.1 channels and regulate them like CaM, whereas myristoylation allows differential, Ca2+-independent regulation by the inactive EF-hands of CaBP1 and VILIP-2, which differ in their positions in the protein structure. Differential, myristoylation-dependent regulation of presynaptic Ca2+ channels by nCaBPs may provide a flexible mechanism for diverse forms of short-term synaptic plasticity.


Subject(s)
Calcium Channels, N-Type/metabolism , Calcium-Binding Proteins/metabolism , Myristic Acid/metabolism , Neurocalcin/metabolism , Neuronal Plasticity/physiology , Animals , Barium/pharmacokinetics , Calcium/metabolism , Calcium Channels, N-Type/genetics , Calcium-Binding Proteins/genetics , Cells, Cultured , Humans , Ion Channel Gating/physiology , Kidney/cytology , Membrane Potentials/physiology , Mutagenesis, Site-Directed , Neurocalcin/genetics , Neurotransmitter Agents/metabolism , Patch-Clamp Techniques , Rats , Transfection
19.
Brain Res ; 1045(1-2): 116-23, 2005 May 31.
Article in English | MEDLINE | ID: mdl-15910769

ABSTRACT

Mechanical forces can alter the gating of several kinds of ion channels in many types of cells, but the mechanisms underlying the mechanosensitivity are not clearly understood. To date, there are very few reports on mechanosensitivity of Ca2+ channels, particularly neuronal Ca2+ channels. We examined the mechanical sensitivity of human recombinant L-type Ca2+ channels in response to fluid flow. Neuronal L-type Ca2+ channels (Ca(v) 1.2) were expressed transiently in HEK293 cells using expression cDNA clones of human alpha1C, alpha2delta, and beta subunits along with green fluorescent protein (GFP) as a reporter protein. Current (I(Ba)) through these heterologously-expressed channels was measured using whole cell recording technique with 20 mM Ba2+ as charge carrier. Transfected cells were exposed to a constant, increased fluid flow from a separate pipette during current recording. The L-type I(Ba) was found to be very sensitive to the flow-induced shear forces. Peak current amplitude increased by as much as approximately 50% during fluid flow as compared to that in the absence of fluid pressure. However, no change was observed in the amplitude of the average current during the final 5 ms of the 150-ms voltage step. Current amplitude promptly returned to normal control levels upon stopping fluid flow. The current-voltage relationship was not altered by fluid flow. The flow-induced increase in current amplitude exhibited an apparent shift in steady-state inactivation toward more negative potentials; inactivation was faster but was not voltage dependent. Activation was slightly faster under flow. Thus, increased mechanical tension associated with fluid flow can alter the fundamental properties of voltage-gated Ca2+ channels, even for channels which might not normally be exposed to fluid flow shear forces in their native environment.


Subject(s)
Barium/metabolism , Calcium Channels, L-Type/genetics , Cell Membrane/physiology , Ion Channel Gating/genetics , Mechanotransduction, Cellular/physiology , Barium/pharmacokinetics , Calcium Channels, L-Type/drug effects , Cell Membrane/drug effects , Cells, Cultured , Extracellular Fluid/metabolism , Humans , Ion Channel Gating/drug effects , Mechanotransduction, Cellular/drug effects , Membrane Potentials/drug effects , Membrane Potentials/physiology , Patch-Clamp Techniques , Recombinant Fusion Proteins/genetics
20.
J Environ Radioact ; 81(2-3): 255-67, 2005.
Article in English | MEDLINE | ID: mdl-15795038

ABSTRACT

Radium is one of the prominent potential contaminants linked with industries extracting or processing material containing naturally occurring radionuclides. In this study we investigate if 133Ba and 85Sr can be used as tracers for predicting 226Ra soil-to-plant transfer. Three soil types were artificially contaminated with these radionuclides and transfer to ryegrass and clover was studied. Barium is considered a better tracer for radium than strontium, given the significant linear correlation found between the Ra and Ba-TF. For strontium, no such correlation was found. The relationship between soil characteristics and transfer factors was investigated. Cation exchange capacity, exchangeable Ca+Mg content and soil pH did not seem to influence Ra, Ba or Sr uptake in any clear way. A significant relation (negative power function) was found between the bivalent (Ca+Mg) concentration in the soil solution and the Ra-TF. A similar dependency was found for the Sr and Ba-TF, although less significant.


Subject(s)
Barium/pharmacokinetics , Radium/pharmacokinetics , Soil Pollutants, Radioactive/pharmacokinetics , Strontium/pharmacokinetics , Barium/analysis , Environmental Monitoring/methods , Lolium/chemistry , Lolium/growth & development , Plant Roots , Radium/analysis , Soil Pollutants, Radioactive/analysis , Strontium/analysis
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