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Biomedical subjects

D E Carter

Publications and source records attributed to D E Carter.

At least 37 records · Page 2Linked to original sources
PubMed1996

Environmental health and hazardous waste issues related to the U.S.-Mexico border.

Environmental health and environmental quality issues along the U.S.-Mexico border have been of concern for several years. The enactment of the North American Free Trade Agreement and the presence of the maquiladoras (foreign-owned industries using imported raw materials) have intensified those concerns recently. Efforts to assess these issues are complicated by the fact that many of the issues affecting the border region are within federal jurisdiction, but the problems are regional and local in nature. Thus, state and local governments become involved with public concerns about real and potential problems. One major problem is that environmental health data from this region are lacking, particularly from Mexico. Some new agencies such as the Border Environment Cooperation Commission, the United States-Mexico Border Health Commission, and the North American Commission on Environmental Cooperation have joined several existing agencies at the federal and state level to address environmental quality and health. Several studies have been initiated to determine air and water quality, but little is being done in the areas of hazardous waste and health assessment. Several problems are anticipated in the generation of such data, such as its format and accessibility. Data gaps and research needs are discussed.

Environmental Health↗
PubMed1996

Inorganic mercury chloride-induced apoptosis in the cultured porcine renal cell line LLC-PK1.

HgCl2 is known to be a renal toxin, but its mechanisms of toxicity are not well understood. The cell line LLC-PK1 was used as a model for renal proximal tubule cells, and the effects of different concentrations of HgCl2 were studied. Apoptosis in response to 35 microM HgCl2 was confirmed by observation of morphological features characteristic of apoptotic cells as well as cleavage of chromosomal DNA into fragments of multiples of 200 base pairs. Ten percent of LLC-PK1 cells in a monolayer underwent apoptosis. These cells detached from the culture flask before apoptosis. Measurement of transepithelial resistance (TER) was used as a functional assay of junctional complex integrity in a novel approach to characterize preapoptotic events in this cell line. Monolayers of LLC-PK1 cells that contained apoptotic cells showed a transient decrease in TER followed by a recovery of TER to the initial levels. The decrease in TER was accompanied by a loss of hemicysts within the monolayer. These data indicate a temporary loss of junctional complexes within the monolayer during apoptosis. One hundred micromolar HgCl2 caused all cells to become necrotic within 3 hr. HgCl2 (10 microM) caused some changes in cell morphology, but no cell death.

Animals↗
PubMed1995

Effect of arsenic exposure on alveolar macrophage function. II. Effect of slightly soluble forms of As(III) and As(V).

The pulmonary toxicity of a substance depends on a number of chemical and physical characteristics, including the solubility of the compounds. In the lung, insoluble forms of metals may be more tumorigenic than soluble forms despite the fact that this effect has not been quantitated and the mechanism of action has not been elucidated. The toxic effects of slightly soluble forms of As(III) and As(V) were evaluated by determining alteration in function of pulmonary alveolar macrophages (PAM) following in vivo and in vitro exposure. Male Sprague-Dawley rats were used throughout. Twenty-four hours following intratracheal instillation of 1 mg/kg (as arsenic) of either arsenic trisulfide (As(III)) or calcium arsenate (As(V)), PAM were lavaged and analyzed for alterations in superoxide (O2-), and tumor necrosis factor (TNF-alpha) production. There were no differences in bronchoalveolar lavage fluid TNF-alpha. PAM lavaged from As(V)-exposed animals showed significant increases in O2- production and in basal release of TNF-alpha. PAM lavaged from animals receiving As(III) did not show significant alterations. To test the direct effects of arsenic, PAM were lavaged from control animals and exposed to concentrations of 0.1 to 300 micrograms/ml arsenic in vitro for up to 24 hr. Doses used were not cytotoxic to PAM, since LDH release was not significantly increased. Significant dose-dependent inhibition of O2- production was only evident after 24 hr exposure to arsenicals. Both As(III) and As(V) produced inhibition at concentrations of 10 micrograms/ml. Suppression of LPS-induced release of TNF-alpha also occurred at similar concentrations for both arsenicals (4-5 micrograms/ml). Neither arsenical inhibited prostaglandin E2 production. Measurement of soluble arsenic concentrations indicated dissolution of the compounds could not account for all of the effects seen. Arsenic-induced alteration in PAM function may compromise host defense.

Animals↗
PubMed1995

An in vitro model for arsine toxicity using isolated red blood cells.

A novel test system using isolated red blood cells (RBCs) and arsine (AsH3) in aqueous solution was developed to allow quantitation of AsH3 exposure and to study the toxicity of AsH3 in vitro. In this system AsH3 gas was generated and dissolved in aqueous solution, the concentration was measured, and the standardized solution was mixed with rat or dog red blood cells (RBCs). AsH3 was found to be stable in solution at neutral pH for several hours, but was lost quickly from solution as the acidity was increased to pH 2. Approximately 74% of the initial 0.56 mM AsH3, measured as total arsenic, was found to be taken up by, or strongly associated with, dog RBCs within 5 min of incubation and 82% of the initial 0.49 mM AsH3 was found in rat RBCs after 10 min incubation. Following hypotonic lysis of rat RBCs, 55% of the cell-associated arsenic was found in the membrane fraction with the balance found in the cytosolic fraction. The in vitro technique was used to examine factors influencing AsH3 toxicity using hemolysis as the end point. Hemolysis levels in dog and rat RBC incubations were found to increase with time after exhibiting a lag phase of about 30 min. At the AsH3 concentrations used, maximum levels of hemolysis were observed by 2 hr; maximum hemolysis at room temperature for dog RBCs was 20% and for rat RBCs was 22%. Increasing the temperature from room temperature to 37 degrees C resulted in increased hemolysis in dog RBCs (36%) and rat RBCs (90%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Interactions of rat red blood cell sulfhydryls with arsenate and arsenite.

Arsenic-thiol interactions were investigated by determining changes in rat blood sulfhydryls after exposure to arsenate, As(V), or arsenite, As(III). Incubation with As(V) resulted in time- and dose-dependent depletion of nonprotein sulfhydryls (NPSH), specifically glutathione (GSH). At the highest As(V) concentration (10 mM), significant loss of glutathione was only observed after 3 h of incubation, but by 5 h 0.5 mM As(V) and higher was sufficient to deplete GSH. As(V) was reduced to As(III) at all dose levels, indicating a redox interaction with GSH, but oxidized glutathione (GSSG) was not formed in sufficient quantities to account for losses in GSH. This may be due to formation of another oxidized species such as a protein-mixed-disulfide (ProSSG). Further evidence that glutathione reduces arsenate was obtained by pretreating cells with the sulfhydryl derivatizing agent N-ethylmaleimide (NEM). Removal of thiols with NEM severely inhibited the formation of As(III) in these incubations, indicating that the main pathway for arsenate reduction in red cells is sulfhydryl dependent. As(III) demonstrated a completely different profile of sulfhydryl interaction. Sulfhydryls (NPSH and GSH) were depleted but the losses were primarily accounted for by oxidation to GSSG. As(III) was also a more potent sulfhydryl depleting agent, requiring only 0.1 mM As(III) to significantly reduce GSH after 5 h of incubation. Significant levels of GSSG formed at all doses of As(III). Evidence is presented to suggest that As(III) also formed mixed complexes with protein and glutathione. Samples that were acid precipitated displayed loss of cytosolic glutathione, which could be reversed if NEM was added prior to protein precipitation. Arsenic was detected in high quantities in the protein precipitates, and this was also found to be reversible by NEM treatment. The fact that both GSH depletion and protein binding were reversible by NEM treatment points to formation of a mixed complex of protein, GSH, and As(III), possibly ProS-As-(SG)x. Arsenic affinity chromatography and polyacrylamide gel electrophoresis were used to characterize arsenic binding proteins in red-cell cytosol. The main arsenic binding protein appeared to be hemoglobin.

Animals↗
PubMed1995

Oxidation-reduction reactions of metal ions.

Several metal or metalloid ions exist in multiple oxidation states and can undergo electron transfer reactions that are important in biological and environmental systems. There are endogenous metal ions such as iron, copper, and cobalt that participate in oxidation-reduction reactions with species of oxygen like molecular dioxygen, superoxide, and hydrogen peroxide. These reactions may be modulated by endogenous reducing agents such as glutathione, ascorbate, and tocopherol. The reactions can be described in terms of thermodynamics through the use of standard electrode potentials. A favorable reaction will depend on the concentrations of the reactants and may depend on the pH and/or on the presence of organic ligands that form complexes with the metal or metalloid. Arsenate (As(V)) can react with glutathione in buffered aqueous solutions to produce arsenite (As(III)) and oxidized glutathione. This reaction may be important in the methylation reactions of arsenic. Arsenic species can decrease the red blood cell levels of reduced glutathione, but the products of oxidation and the mechanism of oxidation are more complex than those found in water alone. Chromium (VI) is thought to interact with DNA after first reacting with a reducing agent such as glutathione to form lower oxidation states of chromium. These examples illustrate the importance of oxidation-reduction reactions for toxic metals and metalloids.

Carcinogens, Environmental↗
PubMed1995

Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices.

The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl2 and NaAsO2 is not clear. The metals are known to react with endogenous sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 10(-4) M HgCl2 or 10(-3) M NaAsO2 +/- stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10(-4) M Hg(SG)2 or 10(-3) M As(SG)3]. Incubations were performed at 37 degrees C in DME-F12 buffer (95/5 O2/CO2) for 8 hr. Hg(SG)2 reduced slice K+/DNA content, as an indicator of viability, significantly less than HgCl2. As(SG)3 exhibited a 2-hr delay in K+/DNA content reduction compared to NaAsO2. This delay in toxicity was not correlated to changes in uptake. Arsenic and mercury accumulation, determined by proton-induced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCl2 cytotoxicity and was correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had limited if any protective effects against cytotoxicity by NaAsO2 and a decrease in As accumulation was not observed. Complex metal-GSH interactions appear to exist and impact on the uptake and toxicity of these metals.

Animals↗
PubMed1994

Effect of arsenic exposure on alveolar macrophage function. I. Effect of soluble as(III) and as(V).

Despite potential differences in the mechanism and potency of toxicity between the two common oxidation states of arsenic (As(III) and As(V)), assessments of the risk from inhaled arsenic generally ignore the oxidation state of inorganic arsenicals. Differences between potency and toxicity of As(III) and As(V) were evaluated by determining alteration in function of pulmonary alveolar macrophages (PAM) following in vivo and in vitro exposure to soluble arsenic. Male Sprague-Dawley rats were used throughout. One day following intratracheal instillation of 1 mg/ml (as arsenic) of either sodium arsenite (As(III)) or sodium arsenate (As(V)), PAM were lavaged and analyzed for alterations in superoxide (O2-), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF-alpha) production. There were no differences in bronchoalveolar lavage fluid PGE2 or TNF-alpha. PAM lavaged from As(V)-exposed animals showed significant increases in O2- production. In vivo exposure to either oxidative form of arsenic decreased basal and lipopolysaccharide (LPS)-induced release of TNF-alpha production by PAM, but did not suppress LPS-induced production of PGE2. To test the direct effects of arsenic on PAM function, PAM were lavaged from control animals and exposed, in vitro, to either arsenical for up to 24 hr to concentrations of 0.1 to 300 micrograms/ml arsenic. Doses used were not cytotoxic to PAM, since LDH release was not significantly increased, even at the highest dose. Significant dose-dependent inhibition of O2- production was only evident after 24 hr exposure to arsenicals. As(III) was more potent than As(V), inhibiting O2- at concentrations as low as 0.1 micrograms/ml compared to 1.0 micrograms/ml of As(V). Suppression of LPS-induced release of TNF-alpha also occurred at lower concentrations of As(III), 50% inhibition at 0.15 micrograms/ml, compared to As(V), 50% inhibition at 1.8 micrograms/ml. While As(III) exposure had no affect on PGE2 production, As(V) caused inhibition of LPS-induced PGE2 production at concentrations above 1.0 micrograms/ml. Differences between As(III) and As(V) indicate that different mechanisms and/or potencies exist between the two arsenic species. Arsenic-induced alteration in PAM function may compromise host defense against infections and alter immune surveillance.

Animals↗
PubMed1994

Tissue distribution and elimination of indium in male Fischer 344 rats following oral and intratracheal administration of indium phosphide.

The use of indium phosphide (InP) in the semiconductor industry has raised concerns about potential occupational exposure. The tissue distribution and elimination of indium were investigated in adult male Fischer 344 rats following either a single or 14 consecutive daily oral doses, or following an intratracheal instillation of InP (10 mg/kg). The concentrations of indium ions in blood, urine, feces, and tissues were quantified either using direct acid digestion followed by electrothermal atomic absorption spectrophotometry (ET-AAS) or using an extraction method with methyltricapryl ammonium ions to remove indium from the matrix followed by ET-AAS. Indium was poorly absorbed from the gastrointestinal tract in both single and multiple oral dose studies. Upon its absorption, indium was relatively evenly distributed among the major organs such as liver, kidney, lung, spleen, and testes. By 96 h after oral dose treatment, less than 0.11% of the dose of indium was recovered from tissues in the single- or multiple-dose experiment. At 96 h, retention of indium in the body was about 0.36% of the dose (except for lung) following intratracheal instillation of InP. Following oral dose administration, the majority of indium was recovered from the gastrointestinal tract and its contents. The high recovery of indium (73% of the dose) in the feces after intratracheal instillation presumably reflects mucociliary clearance and/or biliary excretion of indium. Urinary indium accounted only for 0.08-0.23% of the dose during a 240-h collection period in both single- and multiple-dose studies. It seems that fecal excretion serves as the major route for indium elimination, and this results from poor absorption. Because of the poor absorption of indium following multiple oral doses or intratracheal instillation of InP, it seems unlikely that indium will accumulate in the body following InP exposure.

Administration, Oral↗
PubMed1993

Substrate specificity of rat liver aldehyde dehydrogenase with chloroacetaldehydes.

Chlorinated acetaldehydes have been the focus of research due to their role as reactive intermediates and their possible occurrence in chlorinated drinking water. This study investigated the in vitro substrate specificity of cytosolic and mitochondrial rat liver aldehyde dehydrogenase toward these compounds. Monochloroacetaldehyde was found to be extensively metabolized by these enzymes, to an even greater extent than the standard substrate propionaldehyde. Dichloroacetaldehyde was metabolized to a much lesser extent, and chloral hydrate is not metabolized by this enzyme family. The Km (mM) and Vmax (Vmax for propionaldehyde set to 100) values with the low Km cytosolic enzyme were monochloroacetaldehyde 0.046 and 582, and dichloroacetaldehyde 0.13 and 54.9, and those with the high Km cytosolic enzyme were dichloroacetaldehyde 0.35 and 23.4. The values with the low Km mitochondrial enzyme were monochloroacetaldehyde 0.057 and 462 and dichloroacetaldehyde 0.038 and 12.9, and those with the high Km mitochondrial enzyme were monocloroacetaldehyde 0.024 and 55.5 and dichloroacetaldehyde 0.29 and 3.44. These data suggest that aldehyde dehydrogenase plays a significant role in the metabolism of monochloroacetaldehyde and, to some extent, dichloroacetaldehyde. Some evidence also suggested that alcohol dehydrogenase plays a significant role in the metabolism of dichloroacetaldehyde and chloral hydrate.

Acetaldehyde↗
PubMed1992

Computer databases of medical school curricula.

As the pace of curriculum reform in medical education has accelerated during the past decade, so too have demands on curriculum managers to supply increasingly detailed information about the curriculum. In response, a number of schools have joined together to begin work on designs for computer databases of the curriculum. The authors describe three of the most mature curriculum database prototypes, developed by groups at the medical schools of the University of North Carolina at Chapel Hill (UNC), The University of Maryland, and the University of Miami. All three groups have employed relational database management systems to organize information about each "instructional unit" in the preclinical curriculum, including a set of keywords defining the major concepts presented. The keywords are indexed to a controlled vocabulary, either the Medical Subject Headings (MeSH) or a MeSH derivative. The UNC database also employs a textfile management system to provide users with an overview of the entire curriculum. Future work will focus on identifying a suitable controlled vocabulary; capturing content in greater contextual detail; incorporating alternative learning formats, such as problem-based learning; creating links between content items and examination questions; and capturing information generated by student-patient interactions in clinical settings. As a result of recent collaboration with the Association of American Medical Colleges, work to define a prototype national database has begun and a consortium of interested schools is addressing further development activities.

Abstracting and Indexing↗
PubMed1991

Comparisons among children's responses to the Hand Test by grade, race, sex, and social class.

Four hundred sixty-four children in grades K-8 of an urban school were tested in order to develop norms, check for the presence of developmental trends, and compare the performance of different demographic groups on the Hand Test. Comparisons across grade, race, sex, and socioeconomic class indicated that separate norms for grades, but single norms for race, sex, and socioeconomic levels are appropriate for elementary school children. Discrepancies in the developmental trends raised concern about the validity of indices of psychopathology especially as they apply to children in grades K-8.

Black or African American↗
PubMed1991

Interscorer reliability for the Hand Test administered to children.

The utility of the Hand Test as a quick, reliable measure of 100 children's personalities was assessed. The interscorer reliability of the Hand Test was estimated by both intraclass correlations and the Kappa coefficient for 100 children. Following training, satisfactory intraclass correlations were obtained for the Quantitative scores (20 of 22 above .70) and Qualitative scores (12 of 27 above .70) Kappa coefficients were generally lower. Scorers' memory overload and low response frequency are discussed as possible bases for the low reliabilities of Qualitative scores. Although the Hand Test reliability for Quantitative scores is consistent with those of other projective tests, consideration should be given to the modification of the directions of administration for young children and clarification of scoring rules.

Child↗
PubMed1991

Determination and metabolism of dithiol chelating agents. XII. Metabolism and pharmacokinetics of sodium 2,3-dimercaptopropane-1-sulfonate in humans.

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) is used p.o. for the treatment of chronic lead and Hg intoxication in humans. The metabolism and pharmacokinetics of DMPS were determined after p.o. administration of 300 mg of DMPS to each of 10 normal young men. The absorbed DMPS was metabolized rapidly and extensively to a disulfide form(s). By 24 hr after DMPS administration, the area under the blood concentration-time curve of unaltered DMPS was 3.9 compared to 143 for altered DMPS. Altered DMPS is the difference between total DMPS and unaltered DMPS. Unaltered DMPS is the unbound, parent compound;, total DMPS consists of unaltered DMPS plus oxidized [disulfide] DMPS which is determined after reduction with dithiothreitol. In blood the altered form was confined to plasma. By 15 hr, only 3.7% of the administered DMPS was excreted in the urine as unaltered DMPS and 38.7% as altered DMPS. The unaltered and altered DMPS represented 9 and 91%, respectively, of the total amount of DMPS in the urine. Altered DMPS was converted to unaltered DMPS by treatment with dithiothreitol, which indicates that the altered DMPS is a disulfide(s). There was a high correlation between the urinary excretion of Hg and the urinary excretion of unaltered DMPS (r = 0.920 +/- 0.022 S.E.).

Adult↗
PubMed1990

Comparison of the disposition and in vitro metabolism of 4-vinylcyclohexene in the female mouse and rat.

4-Vinylcyclohexene (VCH) is a chemical to which humans are exposed in the rubber industry. A chronic carcinogenicity bioassay conducted by the National Toxicology Program showed that oral administration of VCH induced tumors in the ovaries of mice but not in those of rats. The hypothesis tested was that the species and organ specificity of VCH toxicity was due to differences in the disposition of VCH between the female rat and mouse. Therefore, the disposition of a single oral dose of 400 mg/kg [14C]VCH was studied in female B6C3F1 mice and Fischer 344 rats. Mice eliminated greater than 95% of the dose in 24 hr, whereas rats required 48 hr to eliminate greater than 95% of the dose. The major routes of excretion of [14C]VCH-derived radioactivity were in the urine (50-60%) and expired air (30-40%). No evidence was obtained to indicate that the ovaries of either species retained VCH as a parent compound or as radioactive equivalents. A dramatic difference was observed between the rat and mouse in the appearance of a monoepoxide of VCH in blood from 0.5 to 6 hr after VCH administration (800 mg/kg, ip). VCH-1,2-epoxide was present in the blood of mice with the highest concentration at 2 hr (41 nmol/ml). The blood concentration of VCH-1,2-epoxide in rats was less than 2.5 nmol/ml at all times examined. VCH-7,8-epoxide was not present in the blood of either species at the level of detection. These findings were supported by in vitro studies of VCH epoxidation by liver microsomes. The rate of epoxidation of VCH (1 mM) to VCH-1,2-epoxide was 6.5-fold greater in mouse liver microsomes than that in rat liver microsomes. The species difference in the rate of epoxide formation by the liver may be an important factor in the species difference in susceptibility to VCH-induced ovarian tumors.

Administration, Oral↗
PubMed1990

Determination and metabolism of dithiol chelating agents: X. In humans, meso-2,3-dimercaptosuccinic acid is bound to plasma proteins via mixed disulfide formation.

meso-2,3-Dimercaptosuccinic acid (DMSA) is orally effective for the treatment of chronic lead intoxication in humans. Earlier studies have shown that the majority of DMSA, given p.o. to normal humans, is excreted in the urine as mixed disulfides with L-cysteine. We have developed an assay for the determination of DMSA that has made possible the determination of the form of DMSA in blood and plasma. After p.o. administration of 10 mg DMSA/kg to four normal young men, no unaltered DMSA (unaltered DMSA is the unbound, parent compound; total DMSA consists of unaltered DMSA plus oxidized (disulfide) DMSA and is determined after reduction with dithiothreitol) was found in the blood over an 8-hr period. Only after treatment of blood or plasma with the disulfide-reducing agent, dithiothreitol, was DMSA detected. This indicates that DMSA is in disulfide linkage with plasma proteins and/or non-protein sulfhydryl compounds. Most of the DMSA in the plasma (92-95%) was found to be bound to plasma proteins, mainly albumin. The remaining DMSA may be bound to small molecular weight (less than 10,000 MW) nonprotein sulfhydryl compounds such as cysteine. Plasma protein appears to serve as a depot and reservoir of DMSA, which can exchange for cysteine. The urinary excretion of unaltered DMSA and DMSA mixed disulfides with L-cysteine suggests that this exchange takes place at the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗