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  • 1
    ISSN: 1432-1041
    Keywords: liver cirrhosis ; coumarin metabolism ; mono-oxygenase activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. The activities of the two kinetic components (high and low affinity) of the microsomal 0-deethylation of 7-ethoxycoumarin have been measured in liver from patients with alcoholic cirrhosis and in normals. 2. The activity (expressed as pmol 7-OH coumarin formed/mg microsomal protein/min) of both components of the enzyme was significantly lower in alcoholic cirrhosis (high affinity=3.27±1.18, low affinity 60.9±11.6) than in normals (high affinity 9.43±2.37, low affinity 111.3±9.2). 3. These results are further evidence that there is a broad impairment of hepatic microsomal mono-oxygenase activity in alcoholic cirrhosis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 559-562 
    ISSN: 1432-1041
    Keywords: ethoxyresorufin 0-deethylase ; alcoholic liver disease ; environmental carcinogens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have investigated the effect of alcoholic liver disease (ALD) on the metabolism of 7-ethoxycoumarin 0-deethylase in human liver microsomes. EROD activity was significantly reduced in tissue from ALD patients who smoked, compared to smoking controls. A similar trend was seen in non-smokers. These results have implications for the metabolism of environmental carcinogens.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : We have previously reported, in an uncontrolled trial, an improvement in fatigue scores in patients with primary biliary cirrhosis given oral antioxidant supplementation. We now present data from a controlled trial.Patients and methods : Sixty-one patients with primary biliary cirrhosis-associated fatigue were randomized into a double-blind, placebo-controlled, cross-over trial. Participants received 12 weeks each of placebo and antioxidant supplementation (vitamins A, C and E, selenium, methionine and ubiquinone) in random order, separated by a 4-week washout period. The primary trial outcome (fatigue) was assessed using the Fisk scale. Other symptoms of primary biliary cirrhosis were measured using Likert and visual analogue scales.Results : Forty-four patients completed both arms of the trial. No significant changes in fatigue were recorded in the active phase of treatment (median improvement in Fisk score, 1; P = 0.61). Small improvements in Fisk scores were recorded during placebo therapy (median improvement, 4; P = 0.03). Neither medication was associated with improvement in any other symptoms related to primary biliary cirrhosis. Adverse effects were more common during active therapy and were mild and self-limiting. One patient died from unrelated causes during active treatment.Conclusions : Although oral antioxidant supplementation appears to be safe, we could not find any evidence for a beneficial effect on fatigue or other liver-related symptoms.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Gastric mucosal alcohol dehydrogenase (ADH) may decrease the bioavailability of ingested ethanol. Because this enzyme is found in highest concentrations in the superficial gastric mucosa, diffuse abnormalities of this tissue could lead to a decrease in the first pass metabolism of ethanol. Methods: Thirty-three adult subjects undergoing routine upper gastrointestinal endoscopy had gastric biopsies performed for assessment of gastric histology and the measurement of gastric ADH activity. Twenty of these subjects underwent separate oral dosing and intravenous infusion of ethanol (0.15 g/kg body weight) in order to determine the first pass metabolism, and hence bioavailability, of ethanol. Results: Gastric histology was normal in 10 of the biopsies, showed chronic gastritis alone in 13 and significant glandular atrophy (i.e. atrophic gastritis) in a further 10. Gastric ADH activity in specimens with normal gastric histology was significantly higher than those with chronic gastritis (P=0.02), and was further decreased in those specimens with significant atrophy (P 〈 0.00001). However, no correlation was found between gastric ADH activity and the first pass metabolism of ethanol (r= 0.09, P=0.9). Conclusions: These results suggest that although gastric ADH activity was decreased in individuals with abnormal gastric mucosa, ethanol bioavailability was not affected by gastric ADH activity. These data support the view that gastric ADH does not play a significant role in the first pass metabolism of alcohol.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 8 (1994), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objective: To determine whether flumecinol (3-trifluoromethyl-α-ethylbenzhydrol, Zixoryn) is effective in ameliorating pruritus of cholestasis, particularly in primary bilary cirrhosis. Methods and Results: 50 patients (46 with primary biliary cirrhosis, PBC) took oral flumecinol 600 mg or identical placebo once weekly for 3 weeks. Patients assessed pruritus by scoring a daily 100 mm visual analogue scale (VAS; 0 = no itch, 100 = severe, continuous, day and night intolerable itch). Quality of life was similarly measured. Patients scored the VAS daily for a 7–day baseline and for a further 21 days. Subjectively, pruritus improved in 13 of 24 on flumecinol and 10 of 26 on placebo (X2= 1.24, P= 0.2 7). Median difference in fall in VAS pruritus score between baseline week (mean score for each individual used) and the last week was 8.0 [95 % confidence interval (CI) –2.1 to 20.81 and for VAS quality of life was 5.0 (95% C1 0.4 to 13.0) both in favour of flumecinol over placebo. Later, 19 patients (all PBC) were randomised to flumecinol 300 mg or placebo daily for 3 weeks. Subjectively, pruritus improved in 7 of 10 on flumecinol and 1 of 9 on placebo (Fisher's exact test, P= 0.02). Median difference in fall in VAS pruritus score was 19.8 mm (95 % CI 3.3 to 40.7 mm) in favour of flumecinol over placebo and for quality of life was 3.5 mm (95 % C1 – 5.9 to 24.9 mm). Flumecinol did not significantly affect liver function tests, antipyrine clearance or serum total bile acids, and was not associated with any significant side-effects. Conclusion: Flumecinol was safe at the above doses and short term treatment with 300 mg daily, significantly ameliorated pruritus in primary biliary cirrhosis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum alpha fetoprotein (AFP) is heterogeneous, one form binding to the lectin concanavalin A (conA) and the other not. The relative amounts, of the two forms in the serum of patients has diagnostic applications in differentiating between primary hepato-cellular carcinoma and metastatic liver disease. In 36 patients with primary hepatocellular carcinoma, the conA-nonreactive form of AFP comprised less than 20% of the total (range 1.6%–19.2%; median 8.7%), whereas in 13 patients with metastatic liver disease the conA-nonreactive form comprised more than 20% of the total (range 26.6%–91.7%; median 57.6%). Four patients with primary hepatocellular carcinoma were treated with CB3717, and serial changes in the serum AFP characteristics were examined. In two patients in whom the total serum AFP concentration fell, the percentage of the conA-nonreactive fraction, initially less than 20% rose steadily. In two other patients the total serum AFP did not fall significantly and the proportion of the conA-nonreactive fraction remained below 20%.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 370 (1976), S. 333-344 
    ISSN: 1432-2307
    Keywords: Paracetamol (acetaminophen) poisoning ; Liver biopsy histopathology ; Centrilobular liver necrosis ; Liver regeneration ; Liver failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 100 patients who had taken an acute overdose of paracetamol the liver was biopsied percutaneously on the 4th day or as soon thereafter as recovery of the clotting mechanism allowed. A system for grading the histological changes in the liver is described. The hallmark of severe (grade III) damage is centrizonal necrosis, for which there is probably a dosage threshold. Consequent changes include phagocytosis of cell debris, reticulin collapse, and an inflammatory infiltration; acidophil degeneration of hepatocytes is sometimes prominent; regenerative growth is already evident after 4 days. Mild (grade I) damage is characterized by excess of lipofuscin pigment in centrizonal hepatocytes, sparse focal necrosis of liver cells, and some phagocytosis of lipofuscin. The findings in moderate (grade II) damage are similar but more pronounced. Five patients died in acute hepatic failure, and 22/100 showed severe (grade III) changes but survived. Forty-nine patients representing all three grades of liver damage were rebiopsied after 3 months. Central necrotic zones were found to have been completely reconstituted leaving only minor abnormalities except for one patient who showed mild centrilobular fibrosis and scarring of a nonprogressive nature.
    Type of Medium: Electronic Resource
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