PubMed Health⌕ Search

Biomedical subjects

J C Bode

Publications and source records attributed to J C Bode.

At least 37 records · Page 2Linked to original sources
PubMed1998

Free methionine supplementation limits alcohol-induced liver damage in rats.

Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accumulation, and energy-rich nucleoside content in the liver of rats with a jejunoileal bypass is demonstrated. The animals obtained 0, 30, and 120 mg of methionine in the control group and 0, 30, 120, and 240 mg in the alcohol-fed group per day and per kilogram of body weight for 12 weeks. Methionine was found to strongly improve the alcohol-induced histological changes in the liver. Triglyceride content of the liver was found to decrease in a dose-dependent manner with increasing methionine ingestion (from 255 +/- 20.7 to 49.7 +/- 6.1 micromol/g of protein in the control group and from 233 +/- 17.3 to 42.1 +/- 7.2 micromol/g of protein in the alcohol group). Hepatic adenosine triphosphate content increased significantly with higher methionine consumption (13.5 +/- 0.8 vs. 26.9 +/- 2.8 micromol/g of protein in the control group and 11.9 +/- 1.4 vs. 20.5 +/- 2.5 micromol/g of protein in the alcohol group), whereas no differences were found in the protein and DNA content of the liver. These results underscore the impairment of the transmethylation/transsulfuration pathway in the development of alcohol-induced liver diseases.

Adenine Nucleotides↗
PubMed1998

Effect of the type of beverage and meat consumed by alcoholics with alcoholic liver disease.

We analyzed meat products and alcoholic beverage preference in patients with the three stages of alcoholic liver disease (ALD) compared with controls using diet history data. Daily consumption of total alcohol, types of alcoholic beverages, and types of meat and meat products in grams was obtained by dietary history taken from patients with biopsy proven stage of ALD. A strong association was found between the ALD subjects and total alcohol and beer consumption. There was a significant increase in the consumption of total pig products, pork, and offal in the ALD groups compared with controls. There was a significant positive correlation between beer consumption and pork in alcoholic hepatitis, total pork products in alcoholic hepatitis, and cirrhosis and offal in alcoholic hepatitis and cirrhosis. There was no correlation with the fatty liver stage of ALD. The strongest correlation was between beer and total pig products in the alcoholic hepatitis group. Wine consumption was negatively correlated with the consumption of pig products and beer in the alcoholic cirrhosis group. In conclusion, the association of total pig product consumption with cirrhosis mortality in various countries was validated by personal diet history data obtained from ALD patients in a tested clinical microcosm. The results suggest that this association may be modified by the type of alcoholic beverage that is preferentially consumed.

Adult↗
PubMed1997

[Risk of hepatitis C virus infection in medical occupations].

Following the introduction of sensitive and specific tests for the detection of hepatitis C virus (HCV) infection studies could be performed to determine the risk to acquire a HCV infection in medical professions. The aim of this report is to summarize the knowledge in this field, especially regarding the risk of transmission of HC virus by injuries with infected material, such as needles. The risk to acquire a HCV infection following needlestick injuries was found to be markedly lower than the risk for transmission of hepatitis B virus infection. In 7 studies from different countries this risk has been found to be between zero to a maximum of 10% (average 2%). When the frequency of HCV infection was studied in occupational groups in hospital (nurses, technical assistants, doctors), it did not differ significantly compared to the prevalence in general population. These and other findings concerning the risk of transmission of HCV infections (between spouses, mother/newborns) clearly show that the risk of transmission of HCV infection is markedly lower than that of HBV infection. These facts should be considered in judging of applications for the recognition of HCV infection as occupational disease.

Adult↗
PubMed1997

[Therapy of hepatitis C].

The purpose of this review is an update of the therapy of hepatitis C especially with Interferon-alpha. From the large number of publications on this topic the established facts were worked out. Taking these facts as a base guidelines for the therapy in practical use were defined. In addition the aspects of therapeutic strategies of chronic hepatitis C which until now can not definitely be judged are discussed. In the relatively few patients in whom hepatitis C is diagnosed already in the acute phase, Interferon-alpha-treatment (3 x 3 million units 3 times a week) for 3 to 4 months increases the percentage of patients in whom HCV-RNA in the serum is eliminated. In patients with chronic hepatitis C, after decision finding for treatment, a standard scheme is recommended which consists of a monotherapy with recombinant Interferon-alpha. The dosage of Interferon-alpha is in the first 12 to 16 weeks 5 up to 6 million units given 3 times a week. For the further therapy 3 million units 3 times a week seems to be appropriate. The recommended duration of Interferon-alpha-therapy is 12 months. A long-term benefit of about 20% can be achieved in unselected groups of patients when judged on the permanent normalisation of serum transaminases and elimination of HCV-RNA in the serum. Important factors which may influence the probability of a sustained response, like HCV genotype, virus titer in serum, duration of the disease, high hepatic iron content and the presence of cirrhosis, are discussed. Up to now there exist no reliable guidelines in the case of a "no change" situation and for patients with a flare-up of inflammatory activity during or after therapy. Combination therapy of Interferon-alpha with other drugs like analogous of nucleotides (for example ribavarin), non steroidal antirheumatic drugs and ursodesoxycholic acid (UDCA) have still to be evaluated in controlled clinical trials.

Dose-Response Relationship, Drug↗
PubMed1997

CYP2E1 activity in patients with alcoholic liver disease.

BACKGROUND/AIMS: In addition to the possible toxicological impact of cytochrome P4502E1 (CYP2E1) in alcohol-induced liver damage, its activity can be regarded as a variable for drug action in patients with alcoholic liver disease as CYP2E1 is involved in the metabolism of several drugs, for example, paracetamol and halogenated anesthetics. The purpose of our study was to acquire detailed knowledge of CYP2E1 activity in patients with progressingly severe manifestations of alcoholic liver disease. METHODS: The concentration ratio of 6-hydroxy-chlorzoxazone/chlorzoxazone in plasma 2 h after ingestion of 500 mg chlorzoxazone (so-called metabolic ratio) has been shown to reflect CYP2E1 activity in vivo. We examined CYP2E1 activity in 56 Caucasian inpatients with minor (n=20), more pronounced (n=14) and severe alcoholic liver disease (n=22). Alcohol abusers were compared to healthy teetotallers (n=14). RESULTS: Metabolic ratios were increased 3-fold in actively drinking (ethanol-induced) compared to abstaining (non-induced) patients with alcoholic liver disease (1.19+/-0.84 vs. 0.44+/-0.45, mean+/-SD, (p<0.0001). CYP2E1 activity was significantly lower in non-induced patients with severe alcoholic liver disease (0.19+/-0.10) than in healthy controls (0.50+/-0.28, p<0.01), abstaining alcohol abusers with minor (0.67+/-0.60, p<0.01) and more pronounced alcoholic liver disease (0.53+/-0.31, p<0.01). When non-induced patients with alcoholic liver disease were arranged in progressing order of liver damage (minor, more pronounced, severe alcoholic liver disease), there was a significant decline in CYP2E1 activity (p=0.0008). CONCLUSIONS: In non-induced patients, CYP2E1 activity decreases in line with severity of alcoholic liver disease. CYP2E1-mediated drug metabolism is significantly impaired in severe alcoholic liver disease.

Adult↗
PubMed1997

Decreased endotoxin-binding capacity of whole blood in patients with alcoholic liver disease.

BACKGROUND/AIMS: The proinflammatory effects of endotoxemia, which is often observed in alcohol-abusing patients with various degrees of liver disease, may be modulated by changes in the concentration of endotoxin binding factors. Therefore, the plasma endotoxin concentration and the overall endotoxin binding capacity of whole blood were measured in these patients. METHODS: Patients with minor (A1; n=27), more pronounced (A2; n=13), cirrhotic alcoholic liver disease (A3; n=18), and non-alcoholic cirrhosis (NC; n=6), and 15 healthy control persons (HC) were included in the study. Endotoxin plasma levels were determined using a standardized limulus assay. A modified assay was applied to additionally detect tightly bound endotoxin. To measure the endotoxin-binding capacity, aliquots of whole blood were incubated with serial dilutions of endotoxin, supernatants were obtained, and endotoxin retrieval was estimated by addition of limulus lysate, followed by photometric measurement of the maximal reaction velocity (dODmax). Endotoxin binding capacity equals the endotoxin concentration at which dODmax reaches a predefined threshold. RESULTS: All groups of alcohol abusers had significantly elevated endotoxin plasma levels with a considerable portion of 'bound' endotoxin. Conversely, the endotoxin binding capacity was markedly diminished, mainly in patients with more advanced liver disease (A1: 85.8% of the control value [non-significant vs. controls]; A2: 25.4% [p<0.05]; A3: 43.6% [p<0.02], NC: 43.2%). CONCLUSIONS: The endotoxin-binding capacity is diminished in patients with alcoholic and non-alcoholic cirrhosis, as well as in less advanced alcoholic liver disease. Reduced endotoxin binding may contribute to the adverse effects of endotoxemia.

Adult↗
PubMed1997

A diet rich in fat and poor in dietary fiber increases the in vitro formation of reactive oxygen species in human feces.

Production of reactive oxygen species in the lumen of the colon, a process that is influenced by nutritional factors, may be important in the etiology of colorectal cancer. Because research on humans in support of this hypothesis is lacking, the objective of this study was to measure the effect of different dietary compositions on the in vitro oxygen radical production in human feces. Over a period of 12 d, seven healthy subjects received a diet rich in fat (50%) and meat and poor in dietary fiber. After a period of 1 wk, they received a vegetarian diet poor in fat (20%) and rich in dietary fiber. At the end of each study period, feces were collected and analyzed for in vitro oxygen radical production with dimethylsulfoxide as the free radical scavenger. The mean hydroxyl radical production was 13 times greater in feces of subjects when they consumed the diet rich in fat and poor in dietary fiber [52.7 +/- 29.5 micromol/(g feces x h)] than when they consumed the diet poor in fat and rich in dietary fiber [3.9 +/- 3.9 micromol/(g feces x h); P < 0.05]. This difference was associated with a 42% higher fecal iron concentration when they consumed the first diet (7.0 +/- 19.2 micromol/g feces) than when they consumed the second (4.9 +/- 1.9 micromol/g feces; P < 0.05). The results of this study confirm that diets high in fat and meat and low in fiber markedly increase the potential for hydroxyl radical formation in the feces, which in turn may contribute to an enhanced risk of colorectal cancer.

Adult↗
PubMed1997

Alcohol's role in gastrointestinal tract disorders.

When alcohol is consumed, the alcoholic beverages first pass through the various segments of the gastrointestinal (GI) tract. Accordingly, alcohol may interfere with the structure as well as the function of GI-tract segments. For example, alcohol can impair the function of the muscles separating the esophagus from the stomach, thereby favoring the occurrence of heartburn. Alcohol-induced damage to the mucosal lining of the esophagus also increases the risk of esophageal cancer. In the stomach, alcohol interferes with gastric acid secretion and with the activity of the muscles surrounding the stomach. Similarly, alcohol may impair the muscle movement in the small and large intestines, contributing to the diarrhea frequently observed in alcoholics. Moreover, alcohol inhibits the absorption of nutrients in the small intestine and increases the transport of toxins across the intestinal walls, effects that may contribute to the development of alcohol-related damage to the liver and other organs.

Alcohol Drinking↗
PubMed1997

Effect of treatment with paromomycin on endotoxemia in patients with alcoholic liver disease--a double-blind, placebo-controlled trial.

The results of experimental and clinical studies support the hypothesis that gut-derived endotoxins might be of relevance for the development and course of alcoholic liver disease. The aim of this study was to test the effect of a nonabsorbable, broad-spectrum antibiotic on endotoxemia in patients with alcoholic liver disease. Fifty patients with alcoholic liver disease (27 with cirrhosis, 23 without cirrhosis) were randomly assigned to receive either paromomycin sulfate (3 x 1 g/day) or placebo in a double-blind fashion for at least 3 weeks, and if possible 4 weeks. Endotoxin concentration, liver function tests, and other laboratory parameters were determined in weekly intervals. Endotoxin concentration was also determined in 15 healthy controls. Groups receiving paromomycin or placebo were similar for clinical and biological items collected initially. Mean initial endotoxin concentrations were significantly elevated in both groups (mean +/- SEM; paromomycin, 16.7 +/- 5.3 pg/ml; placebo, 17.5 +/- 6.9 pg/ml; healthy controls, 2.3 +/- 0.4 pg/ml). Although the mean endotoxin concentration was lower in the verum group after 1 week (paromomycin, 8.0 +/- 1.9 pg/ml; placebo, 14.6 +/- 3.5 pg/ml; p > 0.05), paromomycin treatment had no significant effect on endotoxin concentration or liver function tests during the 4-week period. The beneficial effect of paromomycin treatment on endotoxemia in cirrhotics reported in earlier studies could not be reproduced under the conditions of this trial in patients with alcoholic liver disease.

Adult↗
PubMed1996

Effect of methionine on the fatty acid composition of cellular membranes in rats with chronic ethanol consumption and jejunoileal bypass.

The objective of this study was to investigate the effect of alcohol administration on jejunoileal bypass (JIB)-induced liver dysfunction in rats resulting in abnormalities of fatty acid composition of cell membranes, and whether methionine is able to reverse these changes. Male Wistar rats were subjected to a jejunoileal bypass operation. For 12 weeks, all groups were pair-fed either an alcohol-containing (36% of total calories) liquid diet or a liquid diet in which alcohol was replaced isocalorically by starch. Methionine supplementation in three control groups was 0, 32, 160 and 224 mg/kg body weight/day and the rats in the four alcohol feeding groups received 0, 32, 160 and 224 mg/kg body weight/day. In the alcohol group without any methionine supplementation, higher proportions of oleic and linoleic acid and lower proportions of docosahexaenoic and arachidonic acid became evident in tissue samples of liver and jejunum, in comparison with the other alcohol group. A possible explanation for this reduction in tissue polyunsaturated fatty acid (PUFA) may be a decrease in the activities of delta 6-and delta 5-desaturases, and subsequently a displacement of PUFA from lipid fractions by other fatty acids. Interestingly, in the alcohol group with the highest methionine supplementation, compared to all other alcohol groups, lower proportions of oleic acid and higher proportions of docosahexaenoic acid, appeared. A possible explanation for this increase of PUFA in tissue may be increased activities of delta 6- and delta 5-desaturases.

Alcoholism↗
PubMed1996

Prostaglandin E2 and prostaglandin F2 alpha biosynthesis in human gastric mucosa: effect of chronic alcohol misuse.

BACKGROUND AND AIMS: The results of experimental studies support the hypothesis that decreased prostaglandin production might play a part in the gastric mucosal injury induced by alcohol. In this study, it was investigated whether alcohol misuse impairs the synthesis of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) in gastric mucosa. PATIENTS: Fifty six alcoholic patients and 66 subjects without alcohol misuse were included in the study. METHODS: Mucosal biopsy specimens were obtained from the antrum and body of the stomach. Maximal synthesis rates of PGE2 and PGF2 alpha were determined in the microsomal fraction of the biopsy specimens. RESULTS: The rates of synthesis of both prostaglandins in biopsy specimens from the antrum were not significantly different from those obtained in the body. Synthesis of both prostaglandins was significantly reduced in alcoholic patients who abstained less than five days compared with the non-alcoholic group with normal mucosa (PGE2-40%, PGF2 alpha-42% respectively). In non-alcoholic patients with severe gastritis PGE2 synthesis was increased (+30%, p < 0.05) and PGF2 alpha synthesis was decreased (-42.5%, p < 0.025). In alcoholic patients with severe gastritis PGE2 synthesis was depressed by almost 60% (p < 0.001) compared with the non-alcoholic group with severe gastritis. Neither colonisation of Helicobacter pylori nor smoking had a significant influence on the prostaglandin synthesis. CONCLUSIONS: Chronic alcohol misuse is associated with significantly reduced capacity for prostaglandin synthesis in gastric mucosa and this alcohol induced decrease in prostaglandin synthesis is modulated by the presence and degree of gastritis.

Alcoholism↗
PubMed1996

Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices--final report of a placebo-controlled, double-blind study.

One hundred and six episodes of bleeding from esophageal or gastric varices in 72 patients with cirrhosis of the liver were randomized to treatment either with intravenous terlipressin 2 mg initially and 1 mg every four hours for 24 hours together with bolus injection and continuous infusion of placebo, or with somatostatin 250 micrograms as a bolus and continuous infusion of 250 micrograms/h somatostatin for 24 hours and placebo injections. Standard treatment with transfusions, fluid and electrolyte correction, and lactulose was administered in both groups. In the terlipressin group, 48 out of 53 bleeding episodes (91%) and in the somatostatin group 43 out of 53 bleeds (81%) were initially stopped by the vasoactive drugs. Four of the five bleeds not arrested by terlipressin, and nine of the ten bleeds not arrested by somatostatin, were stopped by balloon tamponade. In one patient in each group variceal bleeding could not be stopped initially, and both patients died. The failure rate of the vasoactive treatment alone, including rebleeds within the study period, was 17% in the terlipressin, and 28% in the somatostatin, group. The initial hemostasis, including balloon tamponade, were 98%, and the definitive bleeding control rates were 89% in both groups. The hospital mortality rate was 21% (11/53) in the terlipressin, and 21% (11/53) in the somatostatin, group. Blood transfusions and duration of bleeding did not differ significantly. The study indicates that a large proportion of bleeds from esophageal and fundic varices can be stopped initially (86%) and definitively controlled (77%) by vasoactive drugs alone.

Adult↗
PubMed1995

Detection of hepatitis C virus antibodies and hepatitis C virus RNA in patients with alcoholic liver disease.

The prevalence of hepatitis C virus (HCV) antibody was determined in 130 patients with alcoholic liver disease using a second-generation anti-HCV enzyme immunoassay (ELISA 2) and confirmed by a sensitive polymerase chain reaction procedure measuring HCV RNA. Hepatic disease was evaluated by clinical and biochemical studies and, whenever possible, by liver biopsy. Seventy-one patients were diagnosed as having cirrhosis, and 59 alcoholic hepatitis (n = 33) or fatty liver (n = 26). The prevalence of anti-HCV in the total group was 9.2% and did not differ significantly in the cirrhotics (11.3%) as compared with the non-cirrhotics (6.8%). HCV RNA was detected in six out of eight cirrhotics and three out of four non-cirrhotics who were ELISA 2 positive. A positive test for antibodies to hepatitis core antigen (anti-HBc) was more frequent in anti-HCV-positive patients (75%) than in the anti-HCV-negative group (14%, P < 0.001). Anti-HBc was also found more frequently in the cirrhotics (25.4%) than in the alcoholics without cirrhosis (11.9%). However, the prevalence of hepatitis B surface antigen was equally low in both groups (cirrhotics 1.4%, non-cirrhotics 1.7%). No correlation was observed between the prevalence of anti-HCV antibodies and the severity of liver dysfunction. These results indicate that HCV, and especially HCV-viraemia, is less frequent in alcoholics in southern Germany than suspected in previous studies, and that the prevalence of HCV markers in alcoholics has been overestimated by ELISA 1 used alone.

Adult↗
PubMed1995

Tumor-necrosis-factor and interleukin-6 response of peripheral blood monocytes to low concentrations of lipopolysaccharide in patients with alcoholic liver disease.

Plasma levels of endotoxin and tumor necrosis factor alpha (TNF alpha) and the cytokine response of isolated monocytes were examined in chronic alcohol abusers with various degrees of liver disease. In 35 patients - 19 with alcoholic fatty liver (AF), 7 with alcoholic hepatitis (AH), 9 with cirrhosis (AC) - and in 15 healthy controls (HC), plasma levels of endotoxin were measured in the limulus assay, and plasma TNF alpha in an immunoassay. The cytokine response of monocytes stimulated in vitro with low doses of endotoxin (range: 25 pg/ml to 2.5 ng/ml) was determined in a cytolytic TNF bioassay and in TNF alpha and interleukin-6 (IL-6) immunoassays. All patient groups had elevated plasma endotoxin levels, whereas plasma TNF alpha was elevated only in AC (43.1 +/- 15.2 vs. HC: 5.0 +/- 1.1 pg/ml). Monocytes from all patient groups released increased amounts of bioactive TNF: AF 5.39 +/- 1.70, AH 7.10 +/- 3.28, AC 2.44 +/- 0.54 vs. HC 1.21 +/- 0.30 ng/ml (stimulation with 2.5 ng/ml endotoxin over 3 hrs.). Similar results were obtained in the TNF alpha immunoassay. Increased release of IL-6 from monocytes was shown only for AF, while values in AC were comparable to those in HC. These data confirm that endotoxemia is frequent in chronic alcoholics. In concert with an increased cytokine response of the monocyte/macrophage system, endotoxemia might contribute to the pathogenesis of alcoholic liver disease.

Adult↗