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Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity
Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
2001 (English)In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 25, no 4, 508-512 p.Article in journal (Refereed) Published
Abstract [en]

Background: Gastric alcohol dehydrogenase may contribute to the metabolism of orally ingested ethanol and decrease the bioavailability of the drug. The aims of this study were to assess the impact of Helicobacter pylori infection and its eradication on gastric alcohol dehydrogenase activity and to relate the findings to gastric histology. Furthermore, the role of age- and sex-related differences in gastric alcohol dehydrogenase activity were studied.

Methods: A total of 76 subjects (39 women and 37 men) underwent upper gastrointestinal endoscopy, and biopsies were obtained from the corpus and antrum. The specimens were used for determining gastric alcohol dehydrogenase activity, histological examination, and urease testing. Subjects with H. pylori infection (n= 36) received medication to eradicate the infection, and repeat biopsies were taken 2 and 12 months later.

Results: No significant difference in gastric alcohol dehydrogenase activity was found between men and women (p > 0.05). Gastric alcohol dehydrogenase activity did not differ significantly between the subjects older than 50 years (n= 39) and those 50 years or younger (n= 37). In subjects with H. pylori infection, gastric alcohol dehydrogenase activity was significantly reduced in the antrum (p < 0.05). After eradication of H. pylori, alcohol dehydrogenase activity in the antrum increased significantly within 2 months (p < 0.01). Antral biopsies with the most pronounced inflammation and histological changes had significantly decreased alcohol dehydrogenase activity (p < 0.05). In contrast, no significant differences were found in corpus.

Conclusions: H. pylori infection is associated with decreased antral alcohol dehydrogenase activity, which seems to be related to the severity of the inflammatory changes in the mucosa. Eradication of H. pylori normalizes antral alcohol dehydrogenase activity within 2 months.

Place, publisher, year, edition, pages
2001. Vol. 25, no 4, 508-512 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-24960DOI: 10.1111/j.1530-0277.2001.tb02243.xLocal ID: 9371OAI: oai:DiVA.org:liu-24960DiVA: diva2:245284
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Clinical Pharmacokinetics of Small Doses of Ethanol: Role of Gastric Emptying and Other Influences in the Upper Gastrointestinal Tract
Open this publication in new window or tab >>Clinical Pharmacokinetics of Small Doses of Ethanol: Role of Gastric Emptying and Other Influences in the Upper Gastrointestinal Tract
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis deals with the clinical pharmacokinetics of small doses of ethanol as influenced by conditions in the proximal gut. The bioavailability of orally administered ethanol depends to a large extent on gastric emptying, which is influenced by pre-treatment with drugs and other clinically relevant factors in the upper gastrointestinal tract.

The impact of the relative amount of carbohydrate, fat or protein in a test meal on the pharmacokinetics of a small dose of ethanol was studied in nine healthy male subjects. Drinking ethanol after eating a meal was compared with intake of the same dose consumed on an empty stomach or given intravenously. The peak blood alcohol concentration (BAC) and the area under the curve (AUC) were greatest when ethanol was given intravenously (100% availability). Drinking ethanol after a meal resulted in considerably lower peak BAC and AUC compared with drinking on an empty stomach. However, the macronutrient composition of the meal had no significant effect on the pharmacokinetics of ethanol as reflected in almost identical blood alcohol curves after high-fat, high-protein, or high-carbohydrate meals.

The decreased bioavailability of ethanol after oral administration compared to intravenous infusion of the same dose can be explained by a first-pass metabolism (FPM). Some investigators attribute this FPM to the presence of alcohol dehydrogenase (ADH) in the gastric mucosa. Gastric ADH activity was studied in mucosal biopsies from 76 patients referred for upper gastrointestinal endoscopy. Those patients (n = 36) infected with H. pylori received treatment to eradicate the bacterium and repeat biopsies were obtained 2 months and one year later. There were no significant differences in gastric ADH activity between males and females and between different age groups. Gastric ADH activity was significantly decreased in the antrum among patients with H. pylori infection. After eradication of H. pylori, gastric ADH activity in the antrum was normalised within two months. No significant differences in the ADH activity were found in biopsies from the corpus. Histological examination of gastric biopsies showed that those exhibiting the most pronounced inflammation and histologic changes had significantly lower ADH activity compared with biopsies judged to have normal histology.

Several drugs inhibit gastric ADH in vitro. Among them acetylsalicylic acid (ASA) was suggested to increase the bioavailability of orally administered ethanol. We studied the effect of low-dose ASA on the pharmacokinetics of a small dose of ethanol in 10 healthy men. Low-dose ASA (75 mg) decreased significantly the peak BAC and the time to reach peak BAC was also prolonged. The underlying mechanism appears to be delayed gastric emptying which was assessed by the paracetamol absorption test. To evaluate the effect of accelerating gastric emptying on ethanol pharmacokinetics, the prokinetic substance cisapride was given to the same 10 subjects. When ethanol was ingested 60 min after a meal pre-treatment with cisapride significantly increased peak BAC. However, this increase in BAC after cisapride was modest compared with the BAC reached when the same dose of ethanol was ingested on an empty stomach. The corresponding serum paracetamol curves indicated that a faster rate of gastric emptying was the main factor responsible for the differences in ethanol pharmacokinetics.

Analysis of breath alcohol concentration (BrAC) is a practical and non-invasive method to estimate the BAC and this technique is used worldwide for forensic purposes. The reliability of BrAC measurements in subjects with gastroesophageal reflux disease (GERD) has been questioned. We therefore compared simultaneously obtained breath and venous blood alcohol concentrations in 10 patients with severe GERD scheduled for antireflux surgery. In one of the experiments gastroesophageal reflux was provoked by applying abdominal compression. Although some patients complained of pronounced reflux symptoms the breath instrument readings of BrAC did not deviate from the corresponding BAC in the two test situations, that is, with and without provocation of reflux.

This thesis has established that measuring alcohol in breath can be used to monitor blood alcohol concentration also in subjects with severe GERD. The relative amount of fat, carbohydrate, or protein in a test meal does not influence the pharmacokinetics of a small dose of ethanol as long as the caloric contents of the meals are similar. The rate of gastric emptying is a major factor determining the bioavailability of orally administered ethanol. Treatment with low-dose ASA (75 mg) delayed gastric emptying and caused a lowering of the peak BAC. The prokinetic drug cisapride, administered under conditions that resemble clinical use, increased the peak BAC by accelerating gastric emptying. However, the drug-induced increase in BAC was much less than the BAC observed after drinking the same dose of ethanol on an empty stomach. H. pylori infection is associated with decreased antral ADH activity related to gastritis. Eradication of H. pylori normalises antral ADH activity within two months.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2001. 68 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 682
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27506 (URN)12162 (Local ID)91-7219-971-7 (ISBN)12162 (Archive number)12162 (OAI)
Public defence
2001-05-25, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-07Bibliographically approved

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Kechagias, StergiosBorch, KurtJones, A. Wayne

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