Biomedical subjects

Christoph Jüngst

Publications and source records attributed to Christoph Jüngst.

7 recordsLinked to original sources

PubMed2006

Gallstone disease: Microlithiasis and sludge.

'Sludge' is the solid material which results from the slow settling of particles dispersed in a liquid medium. Biliary sludge in the gallbladder can be detected by transabdominal ultrasonography, and the typical echoes derive mainly from pigment precipitates mixed with cholesterol crystals. A portion of biliary sludge contains comparatively large particles (1-3 mm) called microliths, the formation of which is an obligatory intermediate step in the development of all types of gallstone. Microlithiasis and sludge in bile may cause colicky pain, cholecystitis, cholangitis, and acute pancreatitis, and are thus of clinical relevance. In these patients treatment follows the guidelines of symptomatic gallstone disease, and strategies include long-term application of ursodeoxycholic acid, endoscopic papillotomy, or preferably laparoscopic cholecystectomy.

Bile↗

PubMed2004

Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects.

BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. METHODS: UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment (p < 0.05). CONCLUSIONS: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.

Adult↗

PubMed2004

Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma.

Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2'-deoxyguanosine (8-oxo-dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C --> T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine DNA glycosylase (hOGG1) and human MutY homolog (hMYH). The aim of this study was to evaluate the extent of oxidative damage and its dependence on the cellular antioxidative capacity and the expression of specific DNA repair enzymes in tumor (tu) and corresponding adjacent nontumor (ntu) liver tissue of 23 patients with histologically confirmed hepatocellular carcinoma. 8-oxo-dG levels, as detected by high-pressure liquid chromatography with electrochemical detection, were significantly (P =.003) elevated in ntu tissue (median, 129 fmol/microg DNA) as compared to tu tissue (median, 52 fmol/microg DNA), and were closely associated with inflammatory infiltration. In ntu tissue, the hepatic iron concentration and malondialdehyde levels were significantly (P =.001) higher as compared to tu tissue. Glutathione content, glutathione peroxidase activity and manganese superoxide dismutase messenger RNA (mRNA) expression did not show statistical differences between ntu and tu tissue. Real-time reverse transcription polymerase chain reaction revealed in tu tissue significantly (P =.014) higher hMTH1 mRNA expression compared to ntu tissue. In contrast, hMYH mRNA expression was significantly (P <.05) higher in ntu tissue. No difference in hOGG1 mRNA expression was seen between tu and ntu. In conclusion, these data suggest that ROS generated by chronic inflammation contribute to human hepatocarcinogenesis. The role of DNA repair enzymes appears to be of reactive rather than causative manner.

Adult↗

PubMed2004

Solubility of cholesterol in the crystal-free gallbladder bile of gallstone patients.

Supersaturation of bile with cholesterol is generally considered the driving force of cholesterol precipitation. However, in most investigations the amount of cholesterol crystals is included in the calculation of the cholesterol saturation index (CSI). We therefore studied the solubility of cholesterol in crystal-free gallbladder bile from gallstone patients. Our results demonstrate significantly ( P <.05) higher CSIs (1.4 +/- 0.5 and 1.4 +/- 0.4 vs 1.1 +/- 0.4, mean +/- SD) in crystal-free gallbladder bile from 66 patients with cholesterol stones and 21 patients with mixed stones compared with those in 30 patients with pigment stones and a significant difference ( P <.001) in the amount of cholesterol in vesicles (19.2% +/- 13.7% and 14.3% +/- 11.6 % vs 4.2% +/- 5.9%) and of the crystal-observation time (COT; 1-21 days, median 2 days and 1-21 days, median 3 days, vs 3-21 days, median 21 days). We detected a positive correlation ( r =.24, P <.01) between the percentage of cholesterol in vesicles and the CSI and a negative correlation between COT and CSI ( r = -.23, P <.02 ) and COT and the percentage of cholesterol in vesicles ( r = -.52, P <.001 ). However, in 14 of 30 gallbladder-bile specimens from patients with pigment stones but in just 5 of 21 specimens from patients with mixed stones patients and 12 of 66 specimens from patients with cholesterol stones, the distribution of cholesterol in different phases (mixed micelles, vesicles, and crystals) was within the limits of solubility determined in previous studies of model bile. Therefore, in addition to the relative composition of biliary lipids, nonlipid components exert considerable influence on the solubility of cholesterol in the gallbladder bile of gallstone patients.

Adult↗

PubMed2004

Ursodeoxycholic acid decreases viscosity and sedimentable fractions of gallbladder bile in patients with cholesterol gallstones.

OBJECTIVES: Ursodeoxycholic acid (UDCA) therapy is associated with reduced risk of biliary pain and acute cholecystitis or pancreatitis in patients with cholesterol gallstones. The underlying mechanisms are understood incompletely, which prompted us to study the influence of UDCA treatment on composition, viscosity and sedimentable fractions of gallbladder bile in 25 patients with symptomatic cholesterol gallstones. METHODS: In two randomised groups, either UDCA (750 mg daily) or placebo was given to each patient 10-12 days before cholecystectomy. Gallbladder bile was collected intraoperatively and analysed for protein, mucin, lipid composition, cholesterol crystal observation time, amount of cholesterol in vesicles, viscosity and sedimentable fractions (cholesterol, protein, mucin, bilirubin). RESULTS: UDCA-treated patients showed longer cholesterol crystal observation times and lower concentrations of total cholesterol and percentages of vesicular cholesterol in gallbladder bile. The concentrations of protein and mucin in gallbladder bile tended to be lower in the UDCA-treated group, but phospholipids, bile acids and bilirubin did not differ between the groups. Viscosity and the total sedimentable fractions of gallbladder bile decreased in the UDCA-treated patients. CONCLUSIONS: UDCA treatment reduces total and vesicular cholesterol, the formation of cholesterol crystals, viscosity, and the total amount of sedimentable fractions in gallbladder bile. These observations might explain, at least partially, why UDCA treatment attenuates the occurrence of biliary pain and complications in gallstone patients.

Adult↗

PubMed2004

Effect of gallbladder mucin on the crystallization of cholesterol in bile.

OBJECTIVES: Mucin is supposed to accelerate the crystallization of cholesterol in model bile while studies in native human gallbladder bile revealed conflicting results. METHODS: Therefore, we determined the relation of mucin concentration and cholesterol crystal observation time in gallbladder bile of 73 patients with cholesterol and mixed and 21 patients with pigment stones. In addition, bile samples of 20 patients with cholesterol gallstones were supplemented with either 0 (control) or 0.5-4.0 mg/ml purified bovine mucin or human mucin isolated from gallbladder bile, to study the effect of variable mucin concentrations on the crystallization of cholesterol. RESULTS: Rapid nucleating biles (</= 4 days, n = 59) showed higher mucin concentrations (0.73 +/- 0.1 mg/ml vs 0.43 +/- 0.07 mg/ml) than biles with longer (> 4 days, n = 35) cholesterol crystal observation times (P < 0.05), but no correlation between mucin concentration and cholesterol crystal observation time was observed. Supplementation experiments with bovine purified mucin (up to 4.0 mg/ml) showed no significant effect on the total amount of newly formed cholesterol crystals within 21 days. However, higher amounts of newly formed cholesterol crystals were seen in bile samples supplemented with human mucin in comparison to negative controls. CONCLUSIONS: Our results demonstrate a dose-dependent effect of human but not of bovine gallbladder mucin on the formation of cholesterol monohydrate crystals in gallbladder bile of patients with cholesterol stones. Therefore, studies of cholesterol crystallization in model bile systems may be valuable but should always be confirmed in native gallbladder bile as the more physiological effector system.

Adult↗

PubMed2002

[Potential role of human DNA-repair enzymes hMTH1, hOGG1 and hMYHalpha in the hepatocarcinogenesis].

To elucidate role of the three enzymes in hepatocarcinogenesis, hMTH1, hOGG1 and hMYH, mRNA expression were examined by using RT/semi-quantitative real-time PCR and 8-O-HdG levels was studied by HPLC/ECD in HCC and non-tumorous liver tissue of 21 patients with hepatocellular carcinoma (HCC). It was found that the 8-OHdG level in non-tumourous liver tissue was significantly higher than in HCC tissue (P = 0.006), and this was correlated with the degree of inflammation. The hMTH1 expression in HCC tissue was significantly higher than in non-tumorous liver tissue (P = 0.014). Inversely, The hMYH alpha expression was significantly increased (P = 0.039) in non-tumorous liver tissue. No difference was seen in hOGG1 expression in non-tumorous liver and HCC tissue. A significant linear correlation between hMTH1 and hOGG1 expression was found both in HCC tissue (r = 0.809, P < 0.001) and in non-tumorous liver tissue (r = 0.883, P < 0.001). Our findings suggested a reactive rather than pathogenic role of the DNA repair enzymes in the hepatocarcinogenesis.

Adult↗