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H K Seitz

Publications and source records attributed to H K Seitz.

At least 73 records · Page 4Linked to original sources
PubMed1992

Human gastric alcohol dehydrogenase: in vitro characteristics and effect of cimetidine.

The presence of at least two types of alcohol dehydrogenase has been demonstrated in surgical specimens from the human stomach. One isoenzyme has a Km of approximately 1-2 mM for ethanol comparable to that of class I alcohol dehydrogenase isoenzyme as defined for the liver. This isoenzyme can also be detected by immunohistology using a polyclonal rabbit antibody against human liver class I alcohol dehydrogenase. The other isoenzyme of alcohol dehydrogenase has a much lower affinity to ethanol (greater than 300 mM), but with activities that become significant at ethanol concentrations of more than 100 mM commonly present in the human stomach. Cimetidine was found to be a noncompetitive inhibitor of gastric alcohol dehydrogenase at concentrations as low as 1 mM in vitro. Since the human gastric alcohol dehydrogenase is responsible for the first-pass metabolism of ethanol, its inhibition by cimetidine may explain the reduced first-pass metabolism of alcohol which is associated with elevated ethanol blood concentrations seen after cimetidine therapy.

Aged↗
PubMed1991

Age-related effects of chronic ethanol intake on vitamin A status in Fisher 344 rats.

The present study was designed to investigate the interaction of age and ethanol on vitamin A status in rats. Rats aged 2 and 19 mo were fed a liquid diet containing 36% of total energy as ethanol or pair-fed a diet containing isoenergetic carbohydrate in place of ethanol. After 3 wk older rats had lower serum retinol (P = 0.04) and higher vitamin A concentrations in liver (P = 0.0001), esophagus (P = 0.0001) and the proximal (P = 0.03) and distal (P = 0.0001) colon than younger animals. Hepatic microsomal cytochrome P-450, retinyl ester hydrolase (REH) and cellular retinol-binding protein (cRBP) were significantly reduced; acyl coenzyme A: retinol acyltransferase (ARAT) was increased; and alcohol (retinol) dehydrogenase (ADH) activity was unchanged with age. Ethanol ingestion increased serum retinol as well as esophageal and colonic vitamin A levels in both age groups. Hepatic cRBP decreased further in the older rats with ethanol feeding, but no change was noted in the percentage of hepatic vitamin A as retinol or retinyl esters. Ethanol ingestion decreased REH (P = 0.0001) and ARAT activities (P = 0.02) and increased cytochrome P-450 (P = 0.04) but had no effect on the activity of ADH in either age group. These data indicate that, regardless of age, chronic ethanol ingestion significantly alters the tissue distribution of vitamin A; however, ethanol reduced cRBP levels only in older rats.

Acyltransferases↗
PubMed1991

Effect of chronic ethanol feeding on hepatic and extrahepatic distribution of vitamin E in rats.

The effect of chronic ethanol feeding on the status of alpha- and gamma-tocopherol in plasma, liver, lung, and testes of Sprague-Dawley rats was characterized. Rats were pair-fed liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates. After 3 weeks, ethanol ingestion resulted in a significant (p less than or equal to 0.05) increase in liver weight and induced fatty liver without affecting total body weight. Ethanol feeding did not affect the plasma concentration of alpha-tocopherol but doubled that of gamma-tocopherol. When expressed per milligram of tissue, liver alpha-tocopherol did not vary with ethanol ingestion, whereas gamma-tocopherol concentration increased 2.5 times that of control animals. However, the concentration of alpha-tocopherol expressed per milligram of total lipids was significantly (p less than or equal to 0.01) decreased in the liver with ethanol feeding. In contrast to the liver, ethanol feeding significantly increased alpha- and gamma-tocopherol levels per milligram of total lipids in the testes. The concentration of gamma-tocopherol (but not alpha-tocopherol) per milligram of lung tissue and per total lung was significantly (p less than or equal to 0.05) increased with ethanol feeding. These data indicate that chronic ethanol ingestion significantly alters the distribution of alpha-tocopherol and gamma-tocopherol in hepatic and extrahepatic tissues of the rat.

Alcoholism↗
PubMed1991

[Thyroxine-binding globulin--not a tumor marker of hepatocellular cancer].

Thyroxin-binding globulin (TBG) is secreted by human hepatoma cell lines and was suggested as a tumor marker of primary hepatocellular carcinoma (HCC). However, the results of several clinical studies are contradictory. Therefore, we decided to investigate whether TBG is a valuable marker for early detection and/or followup of HCC. In 30 patients with HCC we determined TBG, thyroxine (T4), trijodothyronine (T3), alpha-feto-protein, ferritin and the sonographically determined tumor size. Twenty one of these patients had liver cirrhosis. In 19 patients hepatitis B-markers could be detected, 9 of whom with positive HBs antigen. Twenty two patients with liver cirrhosis served as controls. Serum TBG in HCC and liver cirrhosis was not significantly different (21.1 +/- 6.9 vs. 18.7 +/- 5.1 micrograms/ml). T4 (p less than 0.04) and the T4/TBG ratio (p less than 0.0002) were significantly lower in HCC. T3 and ferritin were comparable in both groups. TBG correlated with T4 (r = 0.6), but not with the sonographic tumor size, alpha-fetoprotein or ferritin. In 3 patients alpha-fetoprotein and TBG could be determined 3 to 36 months prior to the primary diagnosis of HCC. In none of these patients an increase of TBG was detected before diagnosis of HCC. In the 4 patients under chemotherapy, TBG decreased after the first course. Three of these patients showed further decreasing TBG values in spite of an increasing tumor size. We conclude that in our patients TBG is no valuable tumor marker for the early diagnosis or follow up of HCC.

Adult↗
PubMed1990

[Menetrier's disease: brain infarction as an unusual first symptom].

A 43-year-old patient was admitted to hospital with an apoplectic stroke caused by an angiographically confirmed partial stenosis of the arteria cerebri media branch. We diagnosed Ménétrier's disease, documented by gastroscopy and histology, after having eliminated other causes for the apoplexy. We suggest a direct causal relationship between the stroke and Ménétrier's disease, since high incidences of thromboembolic complications have been reported in association with this rare disease. After conservative therapy with H2-blockers, laboratory values returned to normal. In the two years following diagnosis, the patient reported no recurrence of neurologic complications.

Adult↗
PubMed1990

Possible role of acetaldehyde in ethanol-related rectal cocarcinogenesis in the rat.

Prospective epidemiologic studies have reported an increased risk of rectal cancer following chronic ethanol ingestion. The effect of ethanol on chemically induced colorectal carcinogenesis is controversial depending on the experimental conditions. In the present study the effect of chronic ethanol administration on acetoxymethylmethylnitrosamine-induced rectal cancer and the possible role of acetaldehyde in this process were investigated. Chronic ethanol administration resulted in an earlier occurrence of rectal tumors in this animal model. Because the concomitant administration of cyanamide, a potent acetaldehyde dehydrogenase inhibitor, showed a positive trend toward increased incidences of tumors, acetaldehyde could be involved in the ethanol-associated carcinogenesis. To measure colonic acetaldehyde, 12 chronically ethanol-fed and control rats received an acute dose of ethanol (2.5 g/kg body wt). The mucosal concentration of acetaldehyde was significantly higher in the rectum compared with the cecum (198 +/- 23 vs. 120 +/- 23 nmoles.g colon-1, p less than 0.05), but was not affected by chronic ethanol feeding. Furthermore, 6 germ-free rats had significantly lower acetaldehyde concentrations in the rectum (84 +/- 11 vs. 234 +/- 33 nmoles.g colon-1, p less than 0.01) and in the cecum (59 +/- 13 vs. 121 +/- 33 nmoles.g colon-1, p less than 0.05) compared with 6 conventional animals, and this was paralleled by the number of fecal bacteria in the 2 intestinal segments. In addition, to determine the effect of chronic ethanol feeding on colorectal cell turnover, 30 animals were pair-fed liquid diets. Using the metaphase-arrest technique, alcohol feeding induced rectal (19.1 +/- 2.0 vs. 9.1 +/- 1.8 cells.crypt-1.h-1, p less than 0.01), but not cecal (18.9 +/- 1.3 vs. 22.2 +/- 3.3 cells.crypt-1.h-1, p greater than 0.05) hyperregeneration. This was accompanied by an increase in the crypt proliferative compartment and increased mucosal ornithine decarboxylase activity (63 +/- 18 vs. 22 +/- 6 pmoles.hr-1.mg protein-1, p less than 0.05). The data show that chronic ethanol ingestion accelerates chemically induced rectal carcinogenesis and raise the possibility that acetaldehyde probably generated through bacterial ethanol oxidation may be involved in this process. The secondary hyperregeneration of the mucosa, observed after alcohol feeding, could by itself favour carcinogenesis.

Acetaldehyde↗
PubMed1990

[Tobacco- and alcohol-associated cancer risk of the upper respiratory and digestive tract].

A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in the ENT Departments of the University hospitals of Heidelberg and Giessen (FRG) provided information on the role of chronic tobacco and alcohol consumption as risk factors in 200 patients and 800 control subjects (4:1 matched design).--Only 4.5% of the tumour patients were non-smokers in contrast to 29.5% in the control group. The average tobacco and alcohol consumption in the patients was more than twice that high than in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer.--It could be demonstrated that tobacco as well as alcohol increased the risk for head and neck cancer, in a dose-dependent fashion, as separate risk factors. In heavy smokers (greater than 60 pack years) a relative risk of 23.4 (alcohol-adjusted) was calculated. For heavy drinkers (greater than 100 g ethanol/day) a relative risk of 21.4 (tobacco-adjusted) was documented. Combined alcohol and tobacco consumption showed a synergistic effect and increased the cancer risk more in an multiplicative than in an additive manner: A daily ethanol consumption of more than 75 g/day combined with more than 50 pack years caused a risk value of 146.2.

Adenocarcinoma↗
PubMed1990

[Lipomatous atrophy of the parotid gland in chronic alcohol consumption].

The effect of chronic ethanol consumption on the morphology of the rat parotid gland was investigated. After feeding an ethanol diet containing 36% of total calories as ethanol for 90 days light microscopic and electron microscopic investigations of the parotid gland tissue showed a striking fat accumulation compared to control rats. Besides interstitial fat tissue dispositions, fat droplets of various size occurred in most of the acinar cells. Additional morphometric investigations revealed a decrease in mean acinar cell volume (-21.9% p greater than 0.001). The latter finding reflects an atrophy of the secretory parenchyma and appears to be responsible for the impaired saliva secretion after chronic ethanol consumption which has been observed in former studies.

Alcohol Drinking↗
PubMed1990

[Dilatation treatment of esophageal stenoses in young patients with recessive epidermolysis bullosa dystrophica].

Recessive dystrophic epidermolysis bullosa is a hereditary disorder affecting both skin and esophageal mucosa. The esophagus is frequently affected resulting in almost complete obstruction. We report here the use of inflatable dilatator balloons as a new treatment of esophageal stenosis in three young patients. Dilatation therapy was tolerated well in all three cases and lead to a long standing success. The patients lived without complaints and they did eat normally up to 2.5 years following dilatation.

Adolescent↗
PubMed1989

Effect of aging on in vivo and in vitro ethanol metabolism and its toxicity in F344 rats.

To investigate the effect of aging on ethanol metabolism, 24 male and female F344 rats aged 2 and 12 mo that were fed a laboratory diet received ethanol (1.2 and 2.5 g/kg body wt) intraperitoneally. In male rats, in vivo ethanol elimination significantly decreased according to age both at high (436 +/- 38 vs. 294 +/- 27 mg/kg.h; p less than 0.01) and low (365 +/- 19 vs. 261 +/- 8 mg/kg.h; p less than 0.01) blood ethanol concentrations. Age did not influence the specific activity of hepatic or gastric alcohol dehydrogenase, whereas the activity was significantly decreased with age in the liver (p less than 0.05) and in the stomach (p less than 0.001) when related to body weight. In addition, the activity of the hepatic microsomal ethanol oxidizing system decreased significantly according to age (8.7 +/- 0.5 vs. 6.00 +/- 0.3 nmol/min.mg micr. protein; p less than 0.001). To study the response of ethanol-metabolizing enzymes to chronic ethanol ingestion, 2- and 19-mo-old male F344 rats were pair-fed nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrate for 3 wk. In this experiment specific alcohol dehydrogenase activity was not significantly affected by age, whereas the hepatic microsomal function estimated by the determination of cytochrome P450, microsomal ethanol oxidizing system, and aniline hydroxylation as well as hepatic mitochondrial low Km-acetaldehyde dehydrogenase activity was found to be markedly depressed with age (p less than 0.01). Chronic ethanol consumption increased microsomal enzyme activities in older rats to levels comparable to those observed in young animals prior to ethanol administration. Chronic ethanol feeding also resulted in an increased hepatic fat accumulation, which was significantly enhanced in older rats. In contrast to male rats, in vivo ethanol metabolism was practically identical for 2- and 12-mo-old female rats. These data demonstrate an enhanced toxicity of alcohol in older compared to younger male but not female rats associated with a delay in alcohol elimination both at high and low ethanol blood concentrations and a decrease in ethanol- and acetaldehyde-metabolizing enzyme activities.

Aging↗
PubMed1989

Effects of acute and chronic ethanol administration on the gastrointestinal hormones gastrin, enteroglucagon, pancreatic glucagon and peptide YY in the rat.

The effect of acute and chronic ethanol administration on the gastrointestinal hormones gastrin, enteroglucagon (EG), pancreatic glucagon (PG) and peptide YY (PYY) was studied in the rat alcohol model. Plasma levels of gastrin and PYY were not significantly changed under chronic and/or acute alcohol, while PG was stimulated by acute intraperitoneal ethanol injections in control animals as well as in chronically ethanol-fed rats (8 +/- 1 vs. 28 +/- 6 pmol/l, p less than or equal to 0.05, and 7 +/- 1 vs. 21 +/- 4 pmol/l, p less than or equal to 0.05). EG levels were significantly raised after chronic ethanol feeding (45 +/- 5 vs. 73 +/- 8 pmol/l, p less than or equal to 0.01) and even further elevated if an acute dose of alcohol was given to chronically ethanol-fed rats (73 +/- 8 vs. 168 +/- 29 pmol/l, p less than or equal to 0.05). The immunohistologically evaluated numbers of the respective hormone-producing cells were not significantly changed by alcohol feeding. The ethanol-dependent elevations of EG and PG may contribute, at least in part, to the intestinal hyper-regeneration, motility disturbances and altered glucose metabolism observed after alcohol consumption.

Animals↗
PubMed1988

[Choledochal cyst. The clinical picture, diagnosis and therapy].

A 21-year-old woman who for more than one year had had epigastric pain which was unrelated to food and radiated belt-like, was found to have a marked increase in gamma-GT, slightly elevated phosphatase activity, and increased erythrocyte sedimentation rate. The diagnosis of choledochal cyst, type Ia, was confirmed by sonography, endoscopic retrograde pancreatography and intravenous cholangiography. A choledochocystojejunostomy with a Y-Roux anastomosis was constructed to stop the cholestasis and prevent complications. The patient became symptom-free after the operation.

Adult↗
PubMed1988

Effect of omeprazole on ethanol oxidation and aniline hydroxylation in rat hepatic microsomes.

Omeprazole, a substituted benzimidazole, is a potent gastric acid antisecretory drug, which inhibits the hepatic oxidative drug metabolism in vitro and in vivo. The effect of omeprazole on the microsomal ethanol oxidizing system (MEOS) and, since ethanol-induced cytochrome P-450 reveals a high activity for aniline hydroxylation, on aniline hydroxylase (AH) has been investigated in rat liver microsomes. Omeprazole inhibits microsomal AH activity significantly in a dose dependent manner, while this was not the case for MEOS activity. These data give indirect evidence that the microsomal metabolism of both ethanol and aniline is mediated by different isoenzymes of cytochrome P-450 and that omeprazole exhibits a different affinity to both compounds. Therefore, it must be emphasized that drug interactions with omeprazole have to be tested experimentally in each individual case, since it is impossible to predict such interactions solely on the knowledge of the drug's metabolic pathway.

Alcohol Oxidoreductases↗
PubMed1987

Increased production, hepatic conjugation, and biliary secretion of bilirubin in the rat after chronic ethanol consumption.

Disturbances of bilirubin metabolism such as jaundice or pigment gallstone formation, or both, occur in alcoholic cirrhosis of the liver. We have studied the influence of chronic ethanol consumption on bilirubin metabolism as well as on biliary calcium and bile acids in 16 pair-fed male rats. The animals received nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates for 4 wk. Bile flow was significantly enhanced after chronic ethanol feeding (p less than 0.05 after 90-min bile collection) and was found to be mainly bile acid-independent. The biliary output and concentration of bilirubin monoconjugates, bilirubin diconjugates, and total calcium was significantly increased (p less than 0.01) in alcohol-fed rats compared with controls. This was not the case for unconjugated bilirubin and for the calcium/bile acid ratio. Hepatic bilirubin uridine-5'-diphosphate-glucuronosyltransferase activity (p less than 0.01), serum total bilirubin (p less than 0.01), and serum free hemoglobin (p less than 0.001) were significantly increased after ethanol consumption. These data provide evidence for enhanced bilirubin production, probably due to hemolysis, after alcohol ingestion. The enhanced bile production is associated with an increased hepatic conjugation and subsequent biliary secretion of bilirubin conjugates. In advanced alcoholic liver disease, these compensatory mechanisms may fail and contribute to the development of jaundice.

Alcohol Drinking↗