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  • 1
    ISSN: 1432-1246
    Keywords: Key words Xylene ; Methylhippuric acid ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: Solvent exposures commonly involve mixtures of substances or mixtures of isomers of a single solvent. These may be metabolised through common pathways, resulting in the potential for metabolic interactions. These may then lead to accumulation of solvent or metabolic intermediates, some of which may be toxic. This paper describes a pilot study conducted to determine the correlation between airborne xylene isomers and the appearance of methylhippuric acid (MHA) isomers in urine of workers exposed mainly to xylene. The project also aimed to determine whether there is preferential metabolism of any isomer by comparison of the ratios of airborne isomers with the ratios of metabolite isomers appearing in urine. Subjects and methods: A total of 12 workers (11 male, 1 female) were recruited into this study, with 2 of the participants providing samples on more than one occasion. Workers included flooring contractors (5), printers (2), chemical manufacturers (2), histology technicians (2) and one householder using a xylene-based varnish. Subjects were aged between 24 and 48 years (37.6 ± 2.0 years; mean ± SEM). After giving informed consent, workers provided a prework and postwork urine sample on a midweek work day. Samples were stored frozen prior to analysis. Breathing-zone air samples were collected using personal air samplers at 50 ml/min. Solvents were trapped on activated-charcoal sampling tubes. Subjects wore pumps for 18–304 (178 ± 24) min on the same day on which urine samples were collected. Results: Xylene exposures ranged from 1.6 to over 7000 ppm. In all, 7 of 16 measurements exceeded the Australian TWA standard of 80 ppm. Two of the flooring contractors wore respiratory protective equipment (RPE) and the two histopathology technicians used workplace ventilation systems. Total urinary MHA output ranged from 10 to 8000 mmol/mol creatinine, with 6 of 16 samples exceeding the modified biological exposure index of 702 mmol/mol. Correlations between airborne concentrations of individual xylene isomers and their corresponding MHA isomers were poor but improved when workers using RPE were excluded from the analysis. Gradients of the regression lines (millimoles of MHA per mole of creatinine per parts per million of xylene) were 3.2 for o-isomers, 7.0 for p-isomers, and 14.4 for m-isomers. Comparisons of isomer ratios of xylene in air were made with the corresponding ratio of MHA isomers in urine. These revealed higher ratios of m-MHA to other MHA isomers than those of m-xylene to the other xylene isomers. The MHA isomer ratios were expected to be the same as the airborne xylene isomer ratios if there were no preferential elimination of any isomer. m-MHA appeared in urine in a greater proportion than would be predicted from the proportion of m-xylene detected in air. The time course of the appearance of MHA isomers in urine also suggests that interactions were taking place, with m-MHA appearing in high proportion in urine following several days of repeated heavy xylene exposure. On a single moderate exposure, m-MHA appeared initially in high proportion in the first few hours but was undetectable in urine after 18 h. p-MHA was detectable for up to 6 h after exposure, and o-MHA remained detectable after 18 h. Conclusions: This study suggests that excretion of m-MHA in urine is favoured over that of the other isomers following exposure to mixed xylenes. This is independent of airborne xylene isomer composition and suggests that the metabolism of m-xylene occurs preferentially to that of the other isomers. It is not clear at which step in the metabolism of xylene this preference occurs, although other work indicates that the initial oxidation of xylene to methylbenzyl alcohol by cytochrome P450 2E1 occurs at the same rate for each isomer. These findings suggest that there is potential for metabolic interactions between xylene isomers and that these may be the basis for xylene toxicity.
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  • 2
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effects of seven day treatment with the nitric oxide synthase (NOS) inhibitorN G-nitro-l-arginine (l-NAME), administered in the drinking water (100 μg/mlad lib) of female guinea pigs. The effects of NOS inhibition were evaluated in naive animals and in guinea pigs with ileitis induced by intraluminal trinitrobenzenesulfonic acid (TNBS). After 7 days, animals were anesthetized, a sterile saline lavage injected into an ileal loop and removed after 30 min for analysis. In naive guinea pigs,l-NAME caused a marked increase in ileal myeloperoxidase activity and conversion of the mucosa from an absorptive to a secretory state. TNBS-treated guinea pigs had a similar, marked increase in granulocyte infiltration and a mucosal secretory response. However, in contrast to naive animals,l-NAME treatment was anti-inflammatory, reverting all responses to the basal state. We conclude that intestinal nitric oxide serves an antiinflammatory role under basal conditions, whereas in the TNBS model of chronic ileitis, nitric oxide is a critical mediator of gut injury.
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  • 3
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of nitric oxide in gut inflammation was evaluated by comparing the effects of selective or nonselective inhibitors of nitric oxide synthase (NOS). Aminoguanidine, a selective inducible NOS (iNOS) inhibitor, or NG-nitro-l-arginine methyl ester (l-NAME) were administered via the drinking water to normal guinea pigs or following induction of ileitis with trinitrobenzene sulfonic acid (TNBS 30 mg/kg). Aminoguanidine had no detectable effect in normal animals. In contrast,l-NAME caused a time and dose-dependent increase in ileal myeloperoxidase activity and circulating leukocyte numbers. Only the ileum was inflamed withl-NAME treatment. In TNBS ileitis, both NOS inhibitors were protective, inhibiting in a dose-dependent manner granulocyte infiltration and submucosal fibrosis, with concurrent reductions in substance P immunoreactivity, epithelial protein leak and bowel wall thickening. Aminoguanidine was remarkably potent with an EC50 value of 100 ng/ml (drinking water concentration).l-NAME was approximately 100-fold less potent than aminoguanidine. We conclude from this pharmacological profile, that a lack of cNOS activity or an excess of iNOS activity can lead to gut inflammation. Aminoguanidine is the most potent inhibitor of experimental inflammatory bowel disease yet reported.
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  • 4
    ISSN: 1420-908X
    Keywords: Nitric oxide ; Inflammation ; Gene expression ; Intestine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We addressed the hypothesis that administration of nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) does not result in a sustained suppression of nitric oxide (NO) synthesis, because of a compensatory expression of inducible nitric oxide synthase (iNOS). L-NAME was administered in the drinking water (0.1–1.0 mg/ml) for 7 days to guinea pigs and rats. Nitric oxide synthesis was assessed by [1] ex vivo formation of nitrite in blood vessels and intestine [2] tissue levels of cGMP [3] iNOS gene expression by RT-PCR [4] NADPH diaphorase staining [5] direct assessment of NO release in tissue explants using a microelectrode/electrochemical detection system. Chronic L-NAME administration elevated intestinal cGMP and nitrite levels in guinea pigs (p〈0.05). In rats, intestinal nitrite levels were comparable in control and L-NAME treatment groups, whereas direct assessment of NO release defined a marked increase in the L-NAME group. Chronic L-NAME resulted in an induction of iNOS gene expression in rats and guinea pigs and novel sites of NADPH diaphorase staining in the intestine. We conclude that iNOS expression is responsible for a compensatory increase or normalization of NO synthesis during sustained administration of L-NAME.
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  • 5
    ISSN: 1432-0649
    Keywords: 42.80 ; 42.30 ; 42.65
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Color phase-conjugate imaging is demonstrated using a multi-colored laser beam. Speed of response, size of the image, clarity of the image, and the intensity of the image are investigated. Color images are stored and recalled without crosstalk between different colors.
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  • 6
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We compared the time course of histamine release with other markers of intestinal injury in a rabbit model of necrotizing enterocolitis. Injury was induced by luminal acetic acid (200 mM) and casein (10 mg/ml) and experiments terminated after 45 min or 3 hr. Compared to saline controls there was a significant elevation of epithelial permeability (51Cr-EDTA clearance) and luminal protein levels at both time points. Luminal fluid histamine levels were approximately 120-fold greater than saline controls at 45 min but were indistinguishable from control values at 3 hr. We conclude that although mast cell activation is a characteristic of this model, elevations in histamine levels are transient.
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  • 7
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of misoprostol pretreatment (100 μg/loop intraluminally) on small intestinal damage induced by acetic acid was evaluated in anesthetized rabbits. In this model injury was induced by intraluminal administration into loops of distal small intestine, of a solution of calcium gluconate (50 mg/ml) and acetic (200 mM). After 3 hr damage was associated with increase in loop fluid volume, loop fluid protein levels and epithelial permeability to51Cr-EDTA, all of which were attenuated by misoprostol pretreatment. Similar protective effects were noted 45 min after the insult, suggesting that misoprostol may be therapeutically useful in conditions where the epithelial barrier is compromised.
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  • 8
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 9
    ISSN: 1520-6904
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
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  • 10
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 61 (1992), S. 450-452 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A new analog memory (AM) has been demonstrated using heterojunction acoustic charge transport (HACT) technology. The initial HACT AMs had storage time capabilities of 100 μs at 25 °C. The Schottky electrode storage array had 36 memory cells, each cell holding 2 charge packets, giving a maximum signal frequency of half the Nyquist frequency. Hold voltages in the 6–8 V range were found to be adequate, and effective storage was obtained at the same dc transport current level that resulted in the best charge transport efficiency. Storage times in the millisecond range are possible with cooling.
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