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Biomedical subjects

K Einarsson

Publications and source records attributed to K Einarsson.

At least 127 records · Page 7Linked to original sources
PubMed1983

Studies of liver insulin receptors in non-obese and obese human subjects.

The insulin-binding isotherms and the structural composition of human liver insulin receptors were examined by using plasma membranes that were prepared from liver biopsies of nine non-obese and 10 obese subjects undergoing elective surgery. The insulin-binding characteristics of liver membranes from non-obese subjects were quite similar to those previously described in rat liver membranes. However, when the membranes from obese subjects were compared with the non-obese group, insulin-binding activity was reduced by 50% (P less than 0.01). The reduction in obesity resulted primarily from a decrease in total receptor number, although a small decrease in receptor affinity was also observed. Insulin binding was not correlated with sex or with the fasting plasma insulin level. The insulin-binding sites of liver membranes were affinity-labeled with 125I-insulin and the cross-linking reagent, disuccinimidyl suberate. The liver membranes from both the non-obese and the obese group had heterogenous (nonreduced) insulin-binding species of 300,000, 260,000, and 150,000 mol wt, which were again comparable to the findings reported in rat liver. Sulfhydryl reduction demonstrated a major sub-unit of 125,000 and a minor component of 40,000-45,000 in both groups. These results indicate a close similarity between the hepatic insulin receptor of man and the more intensely studied rat hepatic receptor. Obesity in human subjects is associated with a loss of hepatic insulin receptors. This alteration may contribute to the insulin resistance reported in this organ as well as to obesity-mediated glucose tolerance.

Adult↗
PubMed1983

14C-triolein breath test as a rapid and convenient screening test for fat malabsorption.

The 14C-triolein breath test was evaluated as a screening test for fat malabsorption in 50 consecutive patients. After the ingestion of a 30-g fat meal containing 5 microCi 14C-triolein, the breath excretion of 14CO2 was measured at hourly intervals for 6 h and compared with a 3-day faecal excretion of fat. Nineteen patients had steatorrhoea and 31 patients normal fat excretion. The maximum specific activity of CO2 in the breath provided the best means of distinguishing between the two groups, with no false-negative values and nine false-positive values (29%). Our findings confirm that the 14C-triolein breath test is sensitive and has sufficient specificity for screening fat malabsorption, especially among outpatients. If a normal 14C-triolein breath test is obtained, it seems unnecessary to perform measurements of excretion of faecal fat.

Adult↗
PubMed1983

Evidence for a lack of regulatory importance of the 12 alpha-hydroxylase in formation of bile acids in man: an in vivo study.

The possibility that the 12 alpha-hydroxylase involved in formation of bile acids is of regulatory importance for the ratio between cholic acid and chenodeoxycholic acid in bile was studied with an in vivo technique. [4-14C]7 alpha-Hydroxy-4-cholesten-3-one and [6 beta-3H]7 alpha, 12 alpha-dihydroxy-4-cholesten-3-one were synthesized, and a mixture of these two bile acid intermediates was administered intravenously in five healthy subjects and in one patient with severe liver cirrhosis. The patient with liver cirrhosis was included in the study because of a considerable reduction in biosynthesis of cholic acid. Since the [4-14C]-labeled steroid is an intermediate just proximal to and since the [6 beta-3H]-labeled steroid is an intermediate just distal to the 12 alpha-hydroxylase step, the 3H/14C ratio in the cholic acid formed should reflect the relative 12 alpha-hydroxylase activity. The 3H/14C ratio varied between 1.8 and 3.9 in the cholic acid isolated from the healthy subjects and was 3.6 in the cholic acid isolated from the patient with liver cirrhosis. The ratio between cholic acid and chenodeoxycholic acid varied between 0.6 and 3.9 in the bile from the control subjects and was only 0.4 in the bile from patients with liver cirrhosis. There was no correlation between the 3H/14C ratios and the ratios between cholic acid and chenodeoxycholic acid in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Comparative effects of ursodeoxycholic acid and chenodeoxycholic acid on bile acid kinetics and biliary lipid secretion in humans. Evidence for different modes of action on bile acid synthesis.

The effects of ursodeoxycholic acid on biliary lipid secretion and bile acid kinetics were determined in 12 men. For comparison, eight of the subjects were also treated with chenodeoxycholic acid using a crossover study design. The daily dose of each bile acid was 15 mg/kg body wt; each treatment period lasted for 5-6 wk. Kinetics of cholic acid and chenodeoxycholic acid, hepatic secretion rates of biliary lipids, and lipid composition of concentrated fasting duodenal bile were determined before and at the end of each treatment period. The synthesis rates of cholic acid and chenodeoxycholic acid were increased by approximately 80% and 40%, respectively, during treatment with ursodeoxycholic acid. The fractional catabolic rates of the two bile acids were increased by approximately 50%, whereas the pool sizes remained unchanged. Under similar conditions, administration of chenodeoxycholic acid reduced the pool size as well as the synthesis rate of cholic acid by approximately 70%. Ursodeoxycholic acid reduced the hepatic secretion of cholesterol to a higher extent (approximately 50%) than did chenodeoxycholic acid (approximately 30%). The secretion rates of bile acids and phospholipids remained essentially unchanged during the two treatment periods. Fasting duodenal (gallbladder) bile was unsaturated with cholesterol during both regimens. It is concluded that the two bile acids exert different effects on bile acid metabolism. The enhanced conversion of cholesterol to bile acids observed during ursodeoxycholic acid treatment may at least partly explain why ursodeoxycholic acid can reduce the biliary output of cholesterol without suppressing hepatic cholesterol synthesis.

Bile↗
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

Effects of interruption of the enterohepatic circulation of bile acids on the transport of very low density-lipoprotein triglycerides.

An increase in plasma very low density lipoprotein-triglycerides (VLDL-TG) is seen frequently during treatment with bile acid-binding resins. The purpose of this study was to determine whether this increment in VLDL-TG is due mainly to an increase in synthesis of VLDL, or to an enhanced catabolism. Three types of patients were studied: (1) 7 normotriglyceridemic subjects. (2) 4 obese patients, and (3) 9 hypertriglyceridemic patients. Before treatment they underwent a study of VLDL-TG kinetics that employed multicompartmental analysis of specific activity curves following injection of 3H-glycerol. The patients were then treated with a bile acid-binding resin, either cholestyramine or colestipol, for several weeks to several months. At the end of the treatment period, they were readmitted to the hospital for a second study of VLDL-TG kinetics. The patients showed a variable response to resin therapy. Many had an increase in concentrations of VLDL-TG, but others had no change or even a slight decrease. However, analysis of the data showed a high correlation between change in production rates of VLDL-TG and change in concentration. Also, when the data for the 20 patients were combined, there was a statistically significant increase in both synthetic rates and concentrations of VLDL-TG; in contrast, the fractional catabolic rate (FCR) was unchanged by therapy. Therefore, our data show that when treatment with bile acid sequestrants causes an increase in plasma VLDL-TG, the increase is due to an increment in production and not to a decrease in catabolism.

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↗
PubMed1982

Lymphatic transport of bile acids in man.

The possibility of a lymphatic transport of bile acids in man was investigated. Four patients were studied 2-4 weeks after renal transplantation. As a part of the postoperative immunosuppressive treatment they all had a thoracic duct fistula for lymphatic drainage. After a standardized meal, lymph and peripheral blood samples were simultaneously collected at 30-minute intervals for 210 minutes. The bile acids, cholic acid, chenodeoxycholic acid, and deoxycholic acid were assayed by a gas-liquid chromatography-mass spectrometry method using deuterium-labeled internal standards. The concentration of cholic acid was about the same in lymph and serum. The concentrations of chenodeoxycholic and deoxycholic acids were 2-3 times higher in lymph than in serum, both in the fasting state and postprandially. These results are explained by a more efficient passive absorption of the less polar dihydroxy bile acids. The transport of bile acids in the lymph was calculated to be only about 0.2% of that in the portal vein.

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

Molecular species of biliary phosphatidylcholines in gallstone patients: the influence of treatment with cholic acid and chenodeoxycholic acid.

Molecular species of phosphatidylcholines were analyzed in hepatic and gallbladder bile obtained from six subjects with adenomyoma of the gallbladder (gallstone-free controls) and 27 gallstone patients undergoing cholecystectomy. Seven of the gallstone patients had been treated with cholic acid and seven with chenodeoxycholic acid for at least 8 weeks before operation. The two predominant species were 1-palmitoyl-2-oleoyl- and 1-palmitoyl-2-linoleoyl-sn-glycerophosphocholines which together accounted for 75-80% of the total amount of phosphatidylcholines. Minor species were 1-palmitoyl-2-palmitoleoyl-, 1-stearoyl-2-linoleoyl-, 1-oleoyl-2-linoleoyl-, and 1-palmitoyl-2-arachidonoyl-sn-glycerophosphocholines. Gallstone patients had a higher portion of the 1-palmitoyl-2-oleoyl species and a concomitant lower proportion of the 1-palmitoyl-2-linoleoyl species than gallstone-free subjects. The ratio between the two species was about 0.7 and 0.4, respectively, in the hepatic bile of the two groups of patients. Treatment with bile acids was associated with a normalization of the pattern of phosphatidylcholines.

Bile↗