The primary goal of this project is to develop microdialysis sampling methods and associated analytical techniques to study gastric ulcers. These techniques will then be used in a comparative study of ulcers induced by Heliobacter pylori and by nonsteroidal anti-inflammatory drugs (NSAIDs). The target analytes in this system include histamine, bicarbonate/pH, N-acetylneuraminic acid (NANA), nitric oxide (NO) and prostaglandins. These compounds play a direct role in ulcer formation, serve a protective role, or are biomarkers for tissue status. Microdialysis sampling will form the basis for these studies and provide capabilities not previously available for studying ulcerated and healthy gastric tissue. Where previously, several animals had to be sacrificed to collect tissue for examination at each time point, microdialysis sampling provides for continuous sampling from the gastric tissue of each experimental animal over extended times. In addition, by implanting microdialysis probes at more than one point in the stomach, both healthy and ulcerated tissue can be studied in the same animal. The project will proceed in three stages. In the first stage, cell culture models will be utilized in vitro. In this manner specific cells lines can be studied in isolation. In the second stage of this project, excised stomach tissue will be used as a model system. Gastric ulcers will be induced by ethanol, acetic acid, indomethacin, and H. pylori. The stomach will then be excised and opened along the greater curvature for in vitro investigation using microdialysis sampling. Microdialysis probes will then be placed into ulcerated and healthy tissue. The final stage of this project will be to examine the healthy and ulcerated stomach tissue in vivo using microdialysis sampling. These methods will then be used in a comparative study of ulcers induced by H. pylori and NSAIDs. In particular, the role of mucus disruption versus acid efflux will be investigated. By continually monitoring the rate of mucus secretion versus acid secretion as a function time, the relative importance of these to processes in ulceration by the various inducers can be determined. This knowledge will aid in the development of advanced preventative and remedial treatments for ulcers resulting from different inducing agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000247-16
Application #
7057826
Study Section
Special Emphasis Panel (ZRG1-SSS-6 (10))
Program Officer
Korte, Brenda
Project Start
1991-06-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
16
Fiscal Year
2006
Total Cost
$246,161
Indirect Cost
Name
University of Kansas Lawrence
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
076248616
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Faiman, Morris D; Kaul, Swetha; Latif, Shaheen A et al. (2013) S-(N, N-diethylcarbamoyl)glutathione (carbamathione), a disulfiram metabolite and its effect on nucleus accumbens and prefrontal cortex dopamine, GABA, and glutamate: a microdialysis study. Neuropharmacology 75:95-105
Whitaker, Gillian; Lunte, Craig E (2010) Investigation of microdialysis sampling calibration approaches for lipophilic analytes: doxorubicin. J Pharm Biomed Anal 53:490-6
Woo, Kristin L; Lunte, Craig E (2008) The development of multiple probe microdialysis sampling in the stomach. J Pharm Biomed Anal 48:20-6
Holovics, Heidi J; Anderson, Carter R; Levine, Barry S et al. (2008) Investigation of drug delivery by iontophoresis in a surgical wound utilizing microdialysis. Pharm Res 25:1762-70
Woo, Kristin L; Lunte, Craig E (2008) The direct comparison of health and ulcerated stomach tissue: a multiple probe microdialysis sampling approach. J Pharm Biomed Anal 48:85-91
Arnett, Stacy D; Lunte, Craig E (2007) Enhanced pH-mediated stacking of anions for CE incorporating a dynamic pH junction. Electrophoresis 28:3786-93
Arnett, Stacy D; Osbourn, Damon M; Moore, Kimberly D et al. (2005) Determination of 8-oxoguanine and 8-hydroxy-2'-deoxyguanosine in the rat cerebral cortex using microdialysis sampling and capillary electrophoresis with electrochemical detection. J Chromatogr B Analyt Technol Biomed Life Sci 827:16-25
Lucas, Laura H; Wilson, Sarah F; Lunte, Craig E et al. (2005) Concentration profiling in rat tissue by high-resolution magic-angle spinning NMR spectroscopy: investigation of a model drug. Anal Chem 77:2978-84
Gillogly, Julie A; Lunte, Craig E (2005) pH-mediated acid stacking with reverse pressure for the analysis of cationic pharmaceuticals in capillary electrophoresis. Electrophoresis 26:633-9
Hoque, Mohammed E; Arnett, Stacy D; Lunte, Craig E (2005) On-column preconcentration of glutathione and glutathione disulfide using pH-mediated base stacking for the analysis of microdialysis samples by capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci 827:51-7

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