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Biomedical subjects

D B Barr

Publications and source records attributed to D B Barr.

30 records · Page 2Linked to original sources

Binding and biological actions of prostaglandin E2 and I2 in cells isolated from rabbit gastric mucosa.

1. We have investigated the binding of the tritiated forms of prostaglandin E2 (PGE2) and a stable analogue of prostacyclin (Iloprost) to isolated cells of rabbit oxyntic mucosa. 2. The highest degree of specific [3H]PGE2 binding occurred in a cellular fraction enriched in parietal cells. [3H]Iloprost binding occurred predominantly in cells identified as mucous cells. 3. PGE2 binding to the parietal cell fraction was associated with its ability to inhibit histamine-stimulated aminopyrine accumulation by these cells. Iloprost binding did not correlate with a biological action on the parietal cells. 4. PGE2 and Iloprost reduced Trypan Blue staining in cells exposed to 10% (w/v) ethanol. Iloprost (10(-8) to 10(-6) M) reduced Trypan Blue staining in cells identified as mucous and parietal cells. PGE2 (10(-8) M) significantly reduced Trypan Blue staining in parietal cell-enriched fractions. 5. Cyclic AMP stimulation in response to either prostanoid occurred most potently on non-parietal cell fractions. However PGE2 or Iloprost binding affinities did not correlate with cyclic AMP formation. 6. These data provide evidence for true PGE2 receptors on oxyntic mucosal cells. The receptors appear to mediate inhibition of acid secretion. Iloprost binds to sites which might mediate cellular protection.

Aminopyrine↗

Ontogeny of gastric mucosal permeability responses to luminal H+ and bile salt in the rat.

Gastric mucosal responses to intraluminal instillation of acid (10, 50, and 150 mM HCl) and acidified solutions of sodium taurocholate (10 mM) were measured in rats between 5 and 60 days after birth. Net loss of H+ and gain of Na+, K+, and protein into the gastric lumen remained low and stable up to 25 days after birth. After that there were dose-dependent increases in H+ loss and Na+ and K+ appearance in the gastric lumen. Luminal protein appearance did not change with any concentration of acid tested in any of the ages examined. Gastric instillation of sodium taurocholate resulted in an increase in the rate of H+ loss as well as Na+ and K+ appearance in neonatal rats after 12-14 days. Protein appeared in the recovered gastric instillate and increased in parallel with Na+ and K+. In response to bile salt treatment, ulcers were only evident after 35 days of age. Injection of 8-day-old rats with corticosterone acetate (250 mg/kg) did not affect the ionic fluxes or protein output in response to acid alone or acidified bile salt solutions. These studies indicate that intragastric acid loads did not increase the ionic permeability of the gastric mucosa until 25 days after birth. The permeability changes occur earlier (day 12-14) if sodium taurocholate is added to the acid instillate. Prior to that time the mucosal permeability characteristics of the neonatal rat stomach are not altered by instillation of either acid loads alone or bile salt solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reference range concentrations of N-acetyl-S-(2-hydroxyethyl)-L-cysteine, a common metabolite of several volatile organic compounds, in the urine of adults in the United States.

N-acetyl-S-(2-hydroxyethyl)-L-cysteine (2-hydroxyethyl mercapturic acid, HEMA) is a urinary metabolite of several hazardous chemicals, including vinyl chloride (VC), ethylene oxide (EO), and ethylene dibromide (EDB). Information about the levels of HEMA in the general population is useful for assessing human exposures to HEMA parent compounds, including VC, EO, and EDB. To establish reference range concentrations for HEMA, we analyzed urine samples from 412 adult participants in the Third National Health and Nutrition Examination Survey (NHANES II) by using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). HEMA was detected in 71% of the samples examined. Creatinine-corrected concentrations ranged from less than 0.68 microg/g creatinine to 58.7 microg/g creatinine; the 95th percentile concentration was 11.2 microg/g creatinine; and the geometric mean and median creatinine-corrected concentrations were both 1.6 microg/g creatinine. We observed a statistically significant difference (P=0.0001) in the creatinine-corrected geometric mean concentration values of HEMA between smokers (2.8 microg/g creatinine) and nonsmokers (1.1 microg/g creatinine). The high levels of HEMA seen among smokers likely originated from HEMA-producing chemicals known to be present in tobacco smoke.

Acetylcysteine↗

Quantification of selected pesticide metabolites in human urine using isotope dilution high-performance liquid chromatography/tandem mass spectrometry.

The annual domestic use of pesticides is continually increasing, virtually ensuring that everyone is exposed to some level of pesticides on a regular basis through diet or environment. The potential developmental and physical adverse effects these chronic pesticide exposures have on children are of increasing concern. To adequately evaluate the potential adverse effects resulting from these exposures, accurate methods to measure the amount of the pesticide absorbed by the body must be developed. We have developed a sensitive method to measure the urinary metabolites of atrazine, diazinon, malathion, 2,4-dichlorophenoxyacetic acid (2,4-D), and certain synthetic pyrethroids in human urine. In our method, stable isotopically labeled analogues of the metabolites were spiked into the urine, which was subsequently extracted at both a neutral and acidic pH using organic solvents. The extracts were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) using atmospheric pressure chemical ionization. Our method has limits of detection ranging from 20 to 500 ng/l (parts per trillion) and relative standard deviations of less than 11%. This method has been used to measure the internal doses of these pesticides in both adults and children (n = 130) with no documented exposure to the pesticides. We detected atrazine and synthetic pyrethroid metabolites in less than 12% of the samples analyzed. The metabolites of 2,4-D, malathion, and diazinon were detected in 22%, 32%, and 57% of the samples, respectively.

Adult↗

Collecting urine samples from young children using cotton gauze for pesticide studies.

To estimate pesticide exposure, urine samples are often needed to analyze pesticide metabolites. However, this is difficult for children wearing diapers because simple and feasible techniques suitable for field collection are not available. The objectives of this study were to test the validity of using cotton gauze pad as a medium for collecting urine samples from young children and to examine the stability of the recoveries for creatinine and pesticide metabolites over 24 h. Urine spiked with a pesticide and four metabolites, 2,4-dichlorophenoxyacetic acid (which is mainly eliminated from urine unchanged), 3-phenoxybenzoic acid (metabolite for synthetic pyrethroids), atrazine mercapturate (metabolite for atrazine), malathion dicarboxylic acid (metabolite for malathion), and 2-isopropyl-4-methyl-6-hydroxypyrimidine (metabolite for diazinon) was added to the gauze pads and kept in jars at 37 degrees C in a water bath. Urine was expressed from the gauze pads immediately and after 1, 2, 4, 8, and 24 h, then analyzed. The recoveries, calculated as the percentage of concentration in expressed urine divided by that of the control urine sample, were within a range of 70-130%. The metabolite and creatinine concentrations did not change with time in either expressed urine samples or controls. The results suggest that cotton gauze pad is a promising candidate for collecting urine samples from young children wearing diapers for studies in which these five urinary pesticide metabolites are to be analyzed.

Child↗

A rapid, sensitive method for the quantitation of N-acetyl-S-(2-hydroxyethyl)-L-cysteine in human urine using isotope-dilution HPLC-MS-MS.

Because of increasing concern about exposure to carcinogens and other toxicants, reliable methods for biological monitoring of potentially exposed populations must be developed. For biological monitoring to be useful, appropriate biomarkers of exposures to xenobiotics must be identified, and sensitive, specific methods for quantifying the targeted biomarker must be developed. We have developed a sensitive and selective method for the analysis of N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA), urinary metabolite of at least three different known human carcinogens (vinyl chloride, ethylene oxide, and ethylene dibromide). The method uses strong anion-exchange solid-phase extraction and isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Our method is simple and is not labor intensive; the preparation time per sample is less than 10 min. Because urine samples vary in both their concentration and ion strength, intersample variability in HEMA recovery during the extraction is large. To overcome this inherent limitation, we use the isotope-dilution technique, which allows a complete correction for the extraction recovery for each sample. The limit of detection of the method is 0.68 microgram/L in a 1-mL urine sample with a coefficient of variation of 22% (determined by replicate analyses at both 4 and 11 micrograms/L) and an accuracy indistinguishable from 100%. Preliminary analyses of urine from a population with no known overt exposure to the parent toxicants show a frequency of detection of approximately 75%, which indicates that this method has the sensitivity to detect urinary HEMA derived from environmental exposure. We are currently using this method to establish a reference range of background exposure to these toxicants in the U.S. population.

Acetylcysteine↗

Autofluorescence in a patient with adult vitelliform degeneration.

The case of an 83 year-old woman is presented in whom bilateral vitelliform macular cysts were observed to fluoresce during the pre-injection phase of intravenous fluorescein angiography. This suggests that the vitelliform response is a non-specific event occurring in retinal pigment epithelial disease in which lipofuscin may or may not be manufactured.

Aged↗

Acquired bilateral superior oblique palsy: a localising sign in the dorsal midbrain.

Bilateral superior oblique palsy is an uncommon ocular motility problem, the commonest cause being closed head trauma. Two cases, both adults, are presented in whom bilateral superior oblique palsy occurred as a result of neoplastic infiltration of the dorsal midbrain in the region of the anterior medullary velum. In the absence of a history of head trauma, the presence of an acquired bilateral superior oblique palsy is a definite sign of a single lesion in the region of the decussation of the trochlear nerves and appropriate imaging is indicated.

Adolescent↗

Strategies for biological monitoring of exposure for contemporary-use pesticides.

Pesticides are used on a massive scale in the United States. The widespread use of these pesticides has made it virtually impossible for the average person to avoid exposure at some level. Generally, it is believed that low-level exposure to these pesticides does not produce acute toxic effects; however, various cancers and other noncancer health endpoints have been associated with chronic exposure to several groups of pesticides. Therefore, it is imperative that well-designed studies investigate the potential relationship between contemporary pesticide exposure and health effects. For these studies to be accurate, reliable methods for determining individual exposure must be used. Biological monitoring is a useful tool for assessing exposure to some contemporary pesticides. As with any analytical method, biological monitoring entails many difficulties, but, in many instances, they can be overcome by the logical use of available information and information acquired in carefully designed studies. At the Centers for Disease Control and Prevention (CDC), we have acquired extensive experience in the development and application of specific techniques for biological monitoring of a variety of toxicants, including many of the contemporary-use pesticides. We have used these methods to measure the internal dose of pesticides received by people in acute and chronic incidents resulting from both environmental and industrial exposure. Additionally, we have established normative values, or reference ranges, of several pesticides based on measurements of their metabolites in the urine of randomly selected adults in the US population. These data have been successfully used to distinguish overt exposures from 'background' exposure. In this paper, we present several examples of the usefulness of biological monitoring in urine and blood and describe the difficulties involved with developing methods in these matrices. We also present a general strategy, considerations, and recommendations for developing biological monitoring techniques for measuring the internal dose of contemporary-use pesticides.

Adult↗