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Biomedical subjects

B Angelin

Publications and source records attributed to B Angelin.

At least 217 records · Page 12Linked to original sources
PubMed1983

Ursodeoxycholic acid treatment in cholesterol gallstone disease: effects on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, biliary lipid composition, and plasma lipid levels.

The present study was undertaken to characterize the effects of ursodeoxycholic acid on biliary lipid metabolism in man. Fifteen gallstone patients were treated with ursodeoxycholic acid at a daily dosage of 15 mg per kg body weight for about 4 weeks before cholecystectomy. At operation a liver biopsy, together with gallbladder and hepatic bile, were obtained. Eighteen untreated gallstone patients undergoing cholecystectomy served as controls. During treatment with ursodeoxycholic acid, hepatic bile became unsaturated with cholesterol in all patients investigated. The total biliary lipid concentration remained unchanged. The hepatic cholesterol concentration decreased by about 20%. No significant change in the microsomal HMG CoA reductase activity was observed (38.5 +/- 6.7 pmol . min-1 . mg protein-1 vs 38.3 +/- 4.7 pmol . min-1 . mg protein-1 in the controls; means +/- SEM). Plasma concentrations of total cholesterol were reduced by about 10%, and those of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol by about 15%. Plasma triglyceride levels remained essentially unchanged during treatment. We conclude that, similar to chenodeoxycholic acid therapy, ursodeoxycholic acid treatment results in unsaturation of fasting hepatic bile. In contrast to the changes seen during chenodeoxycholic acid feeding, however, the unsaturation of hepatic bile during ursodeoxycholic acid treatment is not primarily related to a decreased hepatic HMG CoA reductase activity. Furthermore, while chenodeoxycholic acid tends to increase plasma LDL levels, such changes are not seen during ursodeoxycholic acid treatment.

Adult↗
PubMed1982

Hepatic uptake of bile acids in man. Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum.

This investigation was undertaken in order to (a) characterize the postprandial inflow of individual bile acids to the liver and (b) determine if peripheral venous bile acid levels always adequately reflect the portal venous concentration, or if saturation of hepatic bile acid uptake can occur under physiological conditions. In five patients with uncomplicated cholesterol gallstone disease, the umbilical cord was cannulated during cholecystectomy, and a catheter was left in the left portal branch for 5 to 7 d. The serum concentrations of cholic acid, chenodeoxycholic acid, and deoxycholic acid in portal venous and systemic circulation were then determined at intervals of 15 to 30 min before and after a standardized meal. A highly accurate and specific gas chromatographic/mass spectrometric technique was used. The sum of the fasting concentrations of the three bile acids averaged 14.04+/-4.13 mumol/liter in portal venous serum, and 2.44+/-0.31 mumol/liter in peripheral venous serum. The estimated hepatic fractional uptake of cholic acid was approximately 90%, and those of chenodeoxycholic acid and deoxycholic acid were 70-80%. This resulted in an enrichment of systemic bile acids in the dihydroxy bile acid species. In response to a standardized meal, portal venous bile acid concentrations increased two- to sixfold, with a peak seen 15-60 min after the meal. The maximum postprandial portal venous bile acid concentration averaged 43.04+/-6.12 mumol/liter, and the corresponding concentration in peripheral serum was 5.22+/-0.74 mumol/liter. The estimated fractional uptakes of the individual bile acids were not affected by the increased inflow to the liver. The peripheral venous concentrations of individual as well as total bile acids were well correlated with those in portal venous serum. The results (a) give a quantitation of postprandial bile acid inflow to the liver and (b) indicate that the hepatic uptake system for bile acids in healthy man cannot be saturated during maximal inflow of endogenous bile acids. Measurement of peripheral serum bile acids can thus give important information on the status of the enterohepatic circulation.

Aged↗
PubMed1982

Cholestyramine treatment reduces postprandial but not fasting serum bile acid levels in humans.

Fasting serum concentrations of cholic acid, chenodeoxycholic acid, and deoxycholic acid were determined in healthy subjects and in patients with familial hypercholesterolemia before and during treatment with cholestyramine. The bile acids were analyzed by a specific isotope-dilution technique by using gas chromatography-mass spectrometry. Cholestyramine treatment did not change the fasting concentration of total bile acids, but the contribution of cholic acid was increased; those of chenodeoxycholic acid and deoxycholic acid were decreased. No decrease of fasting bile-acid concentrations in portal venous serum was seen in 2 cholestyramine-treated gallstone patients. The postprandial total bile-acid concentration was about 40% lower during cholestyramine treatment in healthy subjects, reflecting a reduced postprandial inflow of bile acids to the liver. This degree of interruption of the postprandial enterohepatic circulation may be sufficient to produce a near maximal bile-acid biosynthesis rate and to promote lowering of plasma cholesterol also in the fasting state. It is concluded that the postprandial bile-acid inflow to the liver may be more important as a regulator of bile-acid biosynthesis than is the fasting level of bile acids.

Bile Acids and Salts↗
PubMed1982

Hepatic cholesterol metabolism in obesity: activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Obesity is often associated with an elevated total body cholesterol synthesis. In order to evaluate the role of hepatic cholesterogenesis in this phenomenon, we assayed the rate-limiting step in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in the microsomal fraction of liver biopsies obtained operatively from ten morbidly obese (relative body weight greater than 155%) subjects. Eighteen normal-weight patients (relative body weight less than 120%) with cholesterol gallstones served as controls. Hepatic HMG CoA reductase activity, expressed as pmol X min-1 X mg protein-1, was 60% higher in the obese subjects compared to the gallstone patients (P less than 0.05). Microsomal protein concentration was lower in the obese patients, so that enzyme activity calculated per gram liver was not significantly different between the two groups. However, mevalonate formation, expressed in terms of total organ activity, was higher in the obese than in the nonobese group. The results suggest that the liver is a major contributor to the increased cholesterol production seen in obesity.

Adult↗
PubMed1982

Fasting levels of monoketonic bile acids in human peripheral and portal circulation.

It has been suggested that large amounts of ketonic bile acids may be present in portal venous blood. We have therefore determined the approximate concentration of 3-oxo-, 7-oxo-, and 12-oxo-bile acids (monoketonic bile acids) in human peripheral and portal circulation. These compounds were converted into the corresponding 3alpha-, 7alpha-, and 12alpha-hydroxy bile acids by treatment with sodium borodeuteride, thus increasing the molecular weight of each bile acid formed by one mass unit. The ratio between deuterated and nondeuterated bile acid was determined by combined gas-liquid chromatography-mass spectrometry with use of selected ion monitoring. From the ratio obtained and from the concentration of unlabeled bile acid, determined by isotope dilution-mass spectrometry, the approximate concentration of the different ketonic bile acids could be calculated. This method underestimates 3-oxygenated bile acids by 4-8%, 7-oxygenated bile acids by 2-3%, and 12-oxygenated bile acids by about 25%. The approximate concentration of monoketonic 3,7-oxygenated bile acids was found to be 0.08 +/- 0.02 and 0.37 +/- 0.25 micro mol/l in the peripheral venous serum and the portal venous serum, respectively. The approximate concentration of monoketonic 3,12-oxygenated bile acids was found to be 0.07 +/- 0.02 and 0.32 +/- 0.12 micro mol/l in the peripheral venous serum and the portal venous serum, respectively. The approximate concentration of monoketonic 3,7,12-oxygenated bile acids was found to be 0.03 +/- 0.01 and 0.14 +/- 0.05 micro mol/l in the peripheral venous serum and in the portal venous serum, respectively. The total concentration of the ketonic bile acids constituted only 9 +/- 1% and 8 +/- 3% of the nonoxidized bile acids in the peripheral venous serum and in the portal venous serum, respectively. Thus it seems less likely that the portal inflow of ketonic bile acids is of significant physiological importance under normal conditions.-Björkhem, I., B. Angelin, K. Einarsson, and S. Ewerth. Fasting levels of monoketonic bile acids in human peripheral and portal circulation.

Adult↗
PubMed1981

Effects of feeding chenodeoxycholic acid on metabolism of cholesterol and bile acids in germ-free rats.

The aim of this investigation was to study the influence of chenodeoxycholic acid administration on cholesterol and bile acid synthesis in germ-free rats. Seven rats were fed a basal diet and 2 groups of 4 rats received the same diet supplemented with 0.4 and 1% chenodeoxycholic acid, respectively. After 6 weeks, feces were collected in one 3- and one 4-day pool for analysis of cholesterol and bile acids. When the sampling period was finished, the rats were killed and the liver microsomal fractions isolated. The activities of HMG CoA reductase and cholesterol 7 alpha-hydroxylase were determined, the 7 alpha-hydroxylase by a mass fragmentographic method. The 2 dominating bile acids in the untreated rats were cholic acid and beta-muricholic acid. During treatment with chenodeoxycholic acid, 60--70% of this bile acid was converted into alpha- and beta-muricholic acid, indicating a high activity of the 6 beta-hydroxylase. The excretion of cholic acid was almost completely inhibited and the 7 alpha-hydroxylase activity was decreased ca 75% in the rats fed 1% chenodeoxycholic acid. The activity of the hepatic HMG CoA reductase as unchanged. The fecal excretion of cholesterol increased 2--3 times. An accumulation of cholesterol was seen in the rats treated with 1% chenodeoxycholic acid, which was probably a result of the decreased catabolism of cholesterol to bile acids.

Animals↗
PubMed1981

Clofibrate treatment and bile cholesterol saturation: short-term and long-term effects and influence of combination with chenodeoxycholic acid.

In order to determine whether the clofibrate-induced increase in bile cholesterol saturation is transitory, duodenal bile samples were analysed from sixteen hyperlipoproteinaemic patients before and after 6 months to 2 years treatment with clofibrate, 2 g daily. Standardized dietary and weight conditions were obtained. In all but two subjects cholesterol saturation remained elevated (150 +/- 7%, mean +/- SEM) compared to pretreatment values (112 +/- 6%, P less than 0.01). In nine of the patients, duodenal bile was obtained also after 6 weeks of treatment. Although two patients with increased saturation at 6 weeks displayed a return to basal values at 2 years, the majority showed no consistent changes between these two occasions. Addition of chenodeoxycholic acid to clofibrate medication led to a normalization of cholesterol saturation (from 145 +/- 9 to 89 +/- 18%, P less than 0.01) in eight out of nine patients studied. The serum levels of total cholesterol and triglycerides, very low density lipoprotein and high density lipoprotein cholesterol were not significantly changed. However, the low density lipoprotein (LDL) cholesterol concentration was increased by 15--20% (from 4.8 +/- 0.3 to 5.7 +/- 0.4 mmol/l, P less than 0.01). It is concluded that clofibrate induces changes in biliary lipid composition which are consistent over at least 2 years of treatment. Possible measures to avoid these effects must therefore also be taken over a prolonged time. Chenodeoxycholic acid prevents the lithogenic effect of clofibrate but it cannot presently be recommended as an adjunct to clofibrate treatment since it simultaneously causes a rise in the serum concentration of LDL-cholesterol.

Adult↗
PubMed1981

Biliary lipid composition in obesity.

Fasting gallbladder bile was obtained under standardized conditions from 15 gallstone-free obese subjects (greater than 130% of ideal weight) and 23 healthy control subjects matched for age, sex, and serum lipid levels. The proportion of cholesterol, expressed as molar percentage of total biliary lipids, was increased in obesity (10.8 +/- 0.6 versus 6.8 +/- 0.4 M % (mean +/- S.E.M.), P less than 0.001), whereas that of bile acids was decreased (64.7 +/- 1.3 versus 71.0 +/- 1.0 M %, P less than 0.001). The cholesterol saturation of bile was higher in obesity (141 +/- 7%) than in controls (96 +/- 5%, P less than 0.001). The results provide an explanation of the enhanced frequency of cholesterol gallstones in obese subjects.

Bile↗
PubMed1981

Plasma cholesterol esterification rate in type IV hyperlipoproteinemia. Relation to bile acid kinetics and triglyceride metabolism.

The LCAT rate, VLDL triglyceride turnover, and bile acid kinetics were determined under standardized conditions in 10 patients with primary type IV HLP. Bile acid and plasma VLDL triglyceride kinetics were determined with the aid of [14C]-labeled cholic and chenodeoxycholic acid and [3H]glycerol, respectively. The LCAT rate was simultaneously determined in fasting-state plasma. The mean values of total bile acid formation (21.2 +/- 2.6 mumol kg-1 day-1), apparent VLDL triglyceride production (19.6 +/- 2.0 mumol kg-1 hr-1), and LCAT rate (6.0 +/- 0.6 mumol kg-1 hr-1) exceeded those reported previously for healthy controls. Plasma LCAT rate correlated positively with bile acid synthesis (R = 0.85, p less than 0.01) and with apparent plasma VLDL triglyceride production (R = 0.75, p less than 0.02). The results suggest that parallel disturbances in the regulation of cholesterol, bile acid, and lipoprotein metabolism occur in some patients with type IV HLP.

Bile Acids and Salts↗
PubMed1981

Hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and biliary lipid composition in man: relation to cholesterol gallstone disease and effects of cholic acid and chenodeoxycholic acid treatment.

The present work was undertaken in order to study whether or not there is a relation between hepatic HMG CoA reductase, hepatic cholesterol concentration, and biliary lipid composition. In 55 patients (10 with adenomyoma of the gallbladder wall, 45 with cholesterol gallstones) a liver biopsy together with gallbladder and hepatic bile were obtained at laparotomy under standardized conditions. Of the gallstone patients, twelve had been treated with cholic acid and ten with chenodeoxycholic acid in a dose of 15 mg.kg-1.d-1 for 6-8 weeks prior to operation. Hepatic bile was supersaturated with cholesterol both in cholesterol gallstone patients and in patients with gallbladder adenomyoma. Treatment with cholic acid reduced the cholesterol saturation of hepatic bile, although supersaturation persisted. During chenodeoxycholic acid treatment, hepatic bile became unsaturated in most of the patients. Hepatic cholesterol concentration was about 20% higher in patients with cholesterol gallstone disease than in gallstone-free controls. During treatment with cholic acid or chenodeoxycholic acid, hepatic cholesterol concentration was normalized. Microsomal HMG CoA reductase activity was similar in males and females with cholesterol gallstone disease and not different from that seen in the gallstone-free controls. Treatment with chenodeoxycholic acid resulted in a 40% reduction of HMG CoA reductase activity. Cholic acid had no effect. In gallstone-free controls and in bile acid-treated but not in untreated gallstone patients, saturation of hepatic bile correlated with HMG CoA reductase activity. It is concluded that treatment with chenodeoxycholic acid but not with cholic acid results in unsaturated hepatic bile. This unsaturation may in part be explained by a decreased hepatic HMG CoA reductase activity.

Adult↗
PubMed1980

Metabolism of endogenous plama triglyceride in familial hypercholesterolaemia: studies of affected and unaffected siblings of two kindreds.

Plasma endogenous triglyceride kinetics were investigated using [3H]glycerol in five unaffected and eight affected (heterozygous) siblings of two kindreds with familial hypercholesterolaemia. No consistent differences between affected and unaffected siblings regarding plasma triglyceride levels or apparent triglyceride production rates as determined over 10 h were seen, and the values observed were generally within the ranges seen in twelve normolipidaemic controls. It is concluded that abnormal plasma triglyceride metabolism is not a feature of heterozygous familial hypercholesterolaemia.

Adult↗
PubMed1980

Biliary lipid composition in patients with porta cirrhosis of the liver.

Fasting duodenal bile was collected under standardized conditions in 10 male patients with stable portal cirrhosis of the liver and in 12 healthy male controls matched for age, body weight, and serum lipid levels. The proportion of cholesterol, expressed as molar percentage of total biliary lipids, was lower in patients with cirrhosis than in controls (4.6 +/- 0.6 versus 6.4 +/- 0.4 molar %, mean +/- S.E.M.; P less than 0.025), whereas the proportions of bile acids and phospholipids were similar in the two groups. The cholesterol saturation of bile was lower in cirrhotic patients (68 +/- 8%) than in controls (94 +/- 7%; P less than 0.025). The contribution of deoxycholic acid to total bile acids was diminished in cirrhosis and that of chenodeoxycholic acid slightly increased. The results suggest that, in spite of the disturbances of bile acid metabolism generally seen in cirrhosis, such patients are not prone to develop cholesterol gallstones.

Bile↗
PubMed1980

Effects of treatment with chenodeoxycholic acid on liver microsomal metabolism of steroids in man.

The present investigation was undertaken to evaluate whether treatment of gallstone patients with chenodeoxycholic acid is associated with changes of the hepatic metabolism of steroids. Altogether 37 patients with cholesterol gallstones undergoing cholecystectomy were included in the study. Nine of them had been treated with chenodeoxycholic acid (15 mg/kg/day) for about 8 weeks prior to operation. Two hydroxylations involved in cholic acid biosynthesis, 12 alpha-hydroxylation of 7 alpha-hydroxycholest-4-en-3-one and 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, and the metabolism of a physiological steroid hormone, androst-4-ene-3, 17-dione, were studied in the microsomal fraction of liver homogenates. The 12 alpha-hydroxylase was inhibited about 50%, which is in accordance with a regulatory function of this enzyme. The 25-hydroxylase and the metabolism of androst-4-ene,3, 17-dione were unaffected. It is concluded that chenodeoxycholic acid treatment is not associated with general influences on hepatic steroid metabolism.

Androstenedione↗