Study of nitrosating potential at the gastro-oesophageal junction and in Barrett's oesophagus

Suzuki, Hisaharu (2006) Study of nitrosating potential at the gastro-oesophageal junction and in Barrett's oesophagus. MD thesis, University of Glasgow.

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1. A novel technique utilising the microdialysis technique to measure the concentrations of chemicals of nitrosation, nitrite, thiocyanate, ascorbic acid and total vitamin C in the lumen of the human upper gastrointestinal tract was developed and validated in vitro. 2. The recoveries of the chemicals of interest using the microdialysis probes were inversely proportional to the rate of perfusion of the microdialysis probes except for nitrite which was also dependent on the pH of the solution being sampled. We determined the optimal perfusion rate of the microdialysis probes as 0.15mL hr-1 This perfusion rate enabled adequate volumes of microdialysis product to be obtained for subsequent analysis without reducing the recoveries of the chemicals by the microdialysis probe. 3. The microdialysis probe was accurate in sampling the chemicals of interest under dynamic conditions which mimicked the reaction of intermittent delivery of nitrite in swallowed saliva with gastric juice ascorbic acid under both high and low nitrite load. 4. Salivary nitrite in man is derived from the bacterial reduction of dietary nitrate which has undergone entero-salivary recirculation. In the human subjects without gastro-oesophageal reflux, high concentration of nitrite was detected in the saliva and the distal oesophagus following an oral nitrate load. 5. In subjects without gastro-oesophageal reflux, there was an increasing concentration gradient for ascorbic acid and total vitamin C at increasingly distal sites of the upper gastrointestinal tract whereas there was a decreasing concentration gradient for nitrite with virtually no nitrite detectable in the distal stomach. In the acidic stomach, the cardia was the site of greatest ascorbic acid oxidation and also the site of the lowest ascorbic acid to nitrite ratio both before and after an oral nitrate load indicating that the condition for the formation of carcinogenic N-nitrosamines was maximal at this anatomical site in subjects without gastro-oesophageal reflux. 6. Twenty to thirty percent of the nitrate in the saliva is reduced to nitrite by the bacteria within the oral cavity. The nitrate reduction appears to continue within the oesophagus leading to a greater recovery of nitrite to that in the saliva in some subjects. No nitrate reduction was seen within the nasal cavity of healthy subjects. 7. In subjects with Barrett's oesophagus, concentration gradients for ascorbic acid, total vitamin C and nitrite showed a similar pattern to that of the subjects without gastro-oesophgaeal reflux. However, the ascorbic acid to total vitamin C ratio and ascorbic acid to nitrite ratio in the acidic environment were both lowest within the Barrett's segment suggesting that the oxidative stress and the nitrosation potential were greatest within this anatomical site during periods of acid reflux. 8. Within the Barrett's segment the nitrite concentrations fell greatly compared to that of the squamous oesophagus which was attributed to the conversion of acidified nitrite by the gastric juice ascorbic acid to nitric oxide. Using a miniturised nitric oxide sensor and measuring the nitric oxide generation in real-time we were able to demonstrate nitric oxide generation of up to 50muM when saliva came into contact with acidic gastric juice within the Barrett's segment during periods of gastro-oesophageal reflux.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Physiology
Subjects: R Medicine > R Medicine (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: McColl, Professor .
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-71425
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 10:49
Last Modified: 21 May 2021 09:00
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