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Biomedical subjects

F Stickel

Publications and source records attributed to F Stickel.

23 records · Page 2Linked to original sources
PubMedDate not supplied

Effect of alcohol on gastrointestinal cell regeneration as a possible mechanism in alcohol-associated carcinogenesis.

Chronic ethanol consumption is a major risk factor for oropharyngeal, esophageal, and rectal cancer. Because hyperregenerative gastrointestinal mucosa has an increased susceptibility towards chemical carcinogens and thus influences carcinogenesis, various studies have been performed to evaluate the effect of chronic ethanol consumption on mucosal cell turnover. In the rat, morphometric analysis showed that in chronically ethanol-fed rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue, and the base of the tongue were significantly enlarged. The size of the basal cell layer was increased and the stratification of the cells was altered. The percentage of cells in S-phase of the cell cycle was significantly higher in ethanol-fed rats compared to controls. In addition, mucosal atrophy was found. Similar to the oropharynx, in the esophagus chronic ethanol consumption increased cell proliferation depending on salivary gland function, because only in the presence of the salivary glands was this stimulative effect of alcohol on cell turnover found. Subsequently, chronic ethanol ingestion significantly stimulated crypt cell production rate in the rectum, in an age-dependent manner. This hyperregeneration, which was only observed in the rectum but not in the remaining colon, was associated with an expansion of the proliferative compartment of the crypt. Such an expansion is correlated with increased risk for rectal cancer. In addition, crypt cell production rates in the rectal crypts can be correlated with mucosal acetaldehyde concentrations, underlining a toxic effect of acetaldehyde on the rectal mucosa that is answered by compansatory hyperregeneration. These data from the rat model could be confirmed in humans. In conclusion, chronic ethanol consumption leads to mucosal hyperregeneration in gastrointestinal mucosa associated with a high risk for cancer and may therefore be at least one mechanism by which alcohol exerts its cocarcinogenic effect.

Alcohol Drinking↗
PubMedDate not supplied

Helicobacter pylori infection decreases gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol in man.

BACKGROUND/AIMS: Ethanol is metabolized by alcohol dehydrogenase in the human stomach. This metabolism contributes to the so-called first-pass metabolism of ethanol which is affected by gender, medication, and morphological alterations of the gastric mucosa. Recently, it has been shown that Helicobacter pylori is capable to oxidize ethanol to acetaldehyde in vitro. Since H. pylori also injures gastric mucosa, the present study examines the effect of this bacterium on gastric alcohol dehydrogenase activity and systemic availability of ethanol in vivo. METHODS: Thirteen volunteers (7 men and 6 women, aged 18-52 years) with gastric H. pylori infection diagnosed by a positive CLO test and positive gastric histology received ethanol (0.225 g/kg) either orally or intravenously before and after H. pylori elimination to determine systemic availability of ethanol. In addition, gastric biopsy specimens were taken from all subjects before and after H. pylori elimination for histological assessment of mucosal alterations and determinations of gastric alcohol dehydrogenase activity and phenotype of the enzyme. RESULTS: In the presence of H. pylori the first-pass metabolism of ethanol was found to be significantly reduced (625 +/- 234 vs. 1,155 +/- 114 mg/dl/min, p = 0.046). This reduction of first-pass metabolism of ethanol was associated with a significant decrease in alcohol dehydrogenase activity (4.8 +/- 1.5 vs. 12.1 +/- 2.3 nmol/mg protein x min, p < 0.05) and an increase in the severity of mucosal damage as determined by a histological score (p < 0.05). CONCLUSIONS: H. pylori infection leads to gastric mucosal injury which is associated with a decrease in gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol. Ethanol metabolism by H. pylori does not play an important role in vivo. However, gastric morphology is one important factor determining systemic availability of ethanol in man.

Adolescent↗
PubMedDate not supplied

Antifibrotic properties of botanicals in chronic liver disease.

Cirrhosis of the liver is a major complication of various chronic liver diseases and results from excess production and decreased degradation of extracellular matrix. Proinflammatory cytokines, toxic metabolites and certain drugs can trigger enhanced fibrogenesis in hepatic stellate cells and myofibroblasts, the major matrix-producing cells. Since treatment of established cirrhosis is limited, therapeutic interventions that inhibit or mitigate fibrogenesis are needed. Numerous drugs have been investigated for their antifibrotic potential and botanicals constitute a significant fraction of them. Colchicine has been used to treat various chronic liver diseases with controversial results. To date, there is a lack of studies in appropriate animal models and well-controlled human trials to demonstrate its antifibrotic properties. Silymarin has so far failed to clearly show an antifibrotic effect in human studies, whereas animal experiments suggest that this mixture of flavolignanes may be beneficial in patients which have not yet developed cirrhosis. Animal studies indicate an antifibrotic potential of Shosaiko-to, a herbal combination frequently used in China and Japan for the treatment of chronic viral hepatitis, but mechanisms of action need to be further explored. Other botanicals include trans-resveratrol, a flavonoid extracted from grapevine, and Salvia miltiorrhiza which were shown to interfere with the process of hepatic stellate cell activation. Herbal combinations, such as compound 861 and LIV.52 were advocated as antifibrotics or hepatoprotectives, but studies in humans have either been of questionable design or resulted in cessation of the trial due to adverse outcomes.

Animals↗