Biomedical subjects

K Einarsson

Publications and source records attributed to K Einarsson.

At least 55 records · Page 3Linked to original sources

PubMed1991

Age-related changes in the metabolism of cholesterol in rat liver microsomes.

The effects of aging on the hepatic metabolism of cholesterol were studied in 1-, 6- and 24-month-old male Sprague-Dawley rats. Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, which regulates cholesterol biosynthesis, decreased from 835 +/- 144 (SEM) pmol/min/mg protein in the youngest group to 219 +/- 34 and 205 +/- 53 pmol/min/mg protein (p less than 0.001) in the 6- and 24-month-old groups, respectively. Cholesterol 7 alpha-hydroxylase activity, which governs bile acid synthesis, was gradually reduced from 70 +/- 14 pmol/min/mg protein in the 1-month-old group to 32 +/- 7 and 16 +/- 3 pmol/min/mg protein (p less than 0.05) in the 6- and 24-month-old groups, respectively. Acyl coenzyme A:cholesterol acyltransferase activity, which catalyzes the esterification of cholesterol, averaged 431 +/- 47 and 452 +/- 48 pmol/min/mg protein in the 1- and 6-month-old groups, respectively, and was increased to 585 +/- 55 pmol/min/mg protein (p less than 0.05) in the 24-month-old group. The level of total cholesterol showed an age-related increase from 1.56 +/- 0.16 mg/g liver in the 1-month-old group to 1.70 +/- 0.15 and 2.20 +/- 0.19 mg/g liver (p less than 0.05) in the 6- and 24-month-old groups, respectively. The increase was mainly caused by an accumulation of esterified cholesterol. We conclude that a marked decrease in HMG-CoA reductase occurs between 1 and 6 months of age; thereafter the enzyme activity stays unchanged. The activity of cholesterol 7 alpha-hydroxylase decreases progressively and drastically with age, whereas the capacity for esterifying cholesterol increases slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Hepatic metabolism of cholesterol in Crohn's disease. Effect of partial resection of ileum.

To study cholesterol metabolism in Crohn's disease and especially the effect of ileum resection, liver biopsy specimens were obtained from patients undergoing partial ileal resection because of Crohn's disease (n = 17) and patients with Crohn's colitis undergoing colectomy (n = 3). Gallstone-free patients (n = 16) undergoing cholecystectomy because of adenomyomas or polyps of the gallbladder served as controls. The mean levels of cholesterol 7 alpha-hydroxylase activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, rate-determining enzymes in bile acid, and cholesterol synthesis, respectively, were twofold to threefold higher in the ileum-resected patients than in the controls. Significant positive correlations were obtained between length of resected ileum and cholesterol 7 alpha-hydroxylase activity. Provided patients who had received total parenteral nutrition preoperatively were excluded from analysis, a significant correlation was also observed between length of resected ileum and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Significant positive correlations were also obtained between length of resected ileum and serum levels of 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) and lathosterol (a marker for cholesterol synthesis). The plasma levels of total and low-density lipoprotein cholesterol were negatively correlated to the length of resected ileum. The expression of hepatic low-density lipoprotein-receptor binding activity was determined in five of the patients and in three of the controls. A significant positive correlation was observed between 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein-receptor binding activity. The results show that malabsorption of bile acids leads to parallel stimulation of cholesterol synthesis, cholesterol degradation, and low-density lipoprotein-receptor expression in human liver. The resulting effect in the present patients was a significant reduction in low-density lipoprotein cholesterol.

Adult↗

PubMed1991

Effect of cholestyramine treatment on biliary lipid secretion rates in normolipidaemic men.

This study was designed to clarify the effect of bile acid sequestrant treatment on the total biliary output rates of cholesterol, phospholipids and bile acids in man, and to correlate these changes with the alterations in plasma lipoprotein levels. For this purpose nine healthy, normolipidaemic men were treated with 16 g of cholestyramine daily over a period of 4 weeks, and the biliary secretion rates were measured by a duodenal perfusion technique. Resin therapy, which profoundly increases de novo synthesis of bile acids, resulted in a lowering of total plasma cholesterol levels, mainly due to a 35% reduction in low density lipoprotein (LDL) cholesterol, and in a 33% increase in plasma triglyceride levels, reflecting enhanced very low density lipoprotein (VLDL) triglyceride concentrations; high density lipoprotein (HDL) levels did not change. However, these lipoprotein changes did not correlate with any alterations in biliary lipid output. Total hepatic secretion rates of the biliary lipids remained generally unchanged during treatment, with a tendency towards lower cholesterol output, resulting in a lower molar percentage of cholesterol in hepatic bile, 3.4 +/- 0.4 vs. 2.9 +/- 0.2 mol %. This is probably due to an increased rate of conversion of cholesterol to bile acids in the hepatocyte. It is concluded that, in man, the liver may adapt well to changes in the enterohepatic circulation of bile acids, thereby maintaining output rates of biliary lipids at a relatively constant level.

Adult↗

PubMed1991

Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn's disease.

Biliary lipid composition, cholesterol saturation, and bile acid pattern were determined in fasting duodenal bile of 10 patients (four men and six women, mean age 41 years) with Crohn's disease and a history of ileal resection (mean 64 cm). The data were compared with corresponding values in a group of healthy subjects. None of the patients with Crohn's disease had supersaturated bile. Cholesterol saturation was significantly lower in the patients with Crohn's disease than in the healthy subjects. The molar percentage of cholesterol was also lower among the patients but there was no significant difference. The molar percentages of phospholipids and bile acids were normal. Bile acid composition in the patients with ileal resection was characterised by a significant decrease in the deoxycholic acid fraction and a pronounced increase in the ursodeoxycholic acid fraction compared with the healthy subjects. The surprisingly high percentage of ursodeoxycholic acid may contribute to the low degree of cholesterol saturation in bile. Based on these results patients with Crohn's disease should not have an increased risk of cholesterol gall stone formation.

Adult↗

PubMed1991

Nucleation time of gall bladder bile in gall stone patients: influence of bile acid treatment.

The time required for precipitation of cholesterol crystals (nucleation time, NT) was determined and related to the cholesterol saturation in gall bladder bile of gall stone free subjects (n = 11), patients with pigment stones (n = 3), and patients with cholesterol gall stones (n = 30) undergoing cholecystectomy. Seven of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and nine with ursodeoxycholic acid (UDCA), 15 mg/kg/day for three weeks before operation. NT was longer in gall stone free subjects (mean, 20 days), patients with pigment stones (14 days) and patients treated with CDCA (24 days) and UDCA (17 days) compared with untreated patients with cholesterol gall stones (1.5 days). In spite of low cholesterol saturation and prolonged NT, and in contrast to those treated with CDCA, four of the nine patients treated with UDCA had cholesterol crystals in their bile. These observations give further support to the concept that the mechanism for inducing gall stone dissolution may be different for CDCA and UDCA.

Bile↗

PubMed1991

Effect of ursodeoxycholic acid treatment on ileal absorption of bile acids in man as determined by the SeHCAT test.

The effects of urodeoxycholic acid on ileal absorption of bile acids and on serum bile acid and lipoprotein concentrations were studied. Eight healthy subjects were investigated. The gamma emitting bile acid analogue, SeHCAT, was given orally and its fractional catabolic rate and seven day retention were assessed by repeated external counting over the upper abdomen during the next seven days. Ursodeoxycholic acid was then given orally at a dose of 15 mg/kg/day for three weeks and the study was repeated during treatment. The fractional catabolic rate increased by 64% (mean (SD), 0.333 (0.159) v 0.203 (0.061)/day; p less than 0.05) and seven day retention decreased by 44% (15(10) v 27(10)%, p less than 0.001), indicating bile acid malabsorption. Total serum cholesterol fell from 5.79 (1.22) to 5.50 (1.18) mmol/l (p = 0.05), while serum ursodeoxycholic acid increased 22 fold (7.87 (2.67) v 0.34 (0.24) mumol/l, p less than 0.001). Five of the subjects continued taking 30 mg/kg/day of ursodeoxycholic acid for one week and showed an increase in fractional catabolic rate of 81% (0.300 (0.091) v 0.166 (0.037)/day; p less than 0.05) and a fall in seven day retention of 50% (16 (12) v 32 (8)%, p less than 0.01). There were significant reductions in total cholesterol (5.36 (1.71) v 6.08 (1.47) mmol/l; p less than 0.05) and low density lipoprotein cholesterol (3.70 (1.33) v 4.58 (1.16) mmol/l; p less than 0.05). The results support the concept tht ursodeoxycholic acid treatment interferes with the absorption of endogenous bile acids, and emphasise the beneficial effects of this treatment of lipoprotein concentrations in man.

Adult↗

PubMed1991

Influence of age on the metabolism of plasma low density lipoproteins in healthy males.

The plasma concentration of the atherogenic low density lipoproteins (LDL) increases with age. To clarify the mechanism of this change, we studied the kinetics of autologous 125I-LDL apolipoprotein B (apo B) in 41 normolipidemic, nonobese healthy males. For comparison, they were divided into three age groups: young, 21-39 yr (n = 18), middle-aged, 40-59 yr (n = 11), and old, 60-80 yr (n = 12). The levels of plasma LDL cholesterol and LDL apo B increased from respectively 3.4 +/- 0.1 (SEM) mmol/liter and 86 +/- 2 mg/dl in the young to 4.1 +/- 0.1 mmol/liter and 95 +/- 3 mg/dl in the old (P less than 0.01), and this increase was linked to a progressively decreased (r = -0.38, P less than 0.02) fractional catabolic rate of LDL apo B (0.348 +/- 0.010 pools per day in the young vs. 0.296 +/- 0.009 pools per day in the old, P less than 0.01). The production rate of LDL apo B did not differ significantly between the groups. The reduced fractional catabolic rate of LDL apo B in the old was not associated with a decrease in binding affinity of the LDL particle to its receptor, as judged from its ability to compete for 125I-LDL fibroblast binding. When hepatic LDL receptor expression was stimulated by cholestyramine treatment in six old males, their LDL apo B fractional catabolic rate increased to the levels observed in the young subjects. We conclude that the increase in LDL which normally occurs with age is explained by a reduced capacity for its removal, and hypothesize that this is mediated via a reduced hepatic LDL receptor expression.

Adult↗

PubMed1991

Vasoactive intestinal peptide and secretin: effects of combined and separate intravenous infusions on bile secretion in man.

The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion bile volume increased by 60%, and during the combined VIP and secretin infusion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentrations decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [14C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.

Adult↗

PubMed1991

Neurophysiologic studies of patients with Crohn's disease on long-term treatment with metronidazole.

Fifty-three patients with Crohn's disease were chosen for this study. They were divided into three groups: the first group (19 patients) was treated with metronidazole and had been receiving the drug for at least 1 year; the second group (13 patients) had previously had the same type of long-term treatment but had been off the drug for at least 3 months before entering the study; the third group (21 patients) had never received treatment with metronidazole. The maximum daily dose of metronidazole used was 800 mg. All patients were examined with a broad set of neurophysiologic investigations devised to reveal signs of peripheral neuropathy. No significant difference was found between the three groups. The conclusion was that a daily dose of metronidazole not exceeding 800 mg is well tolerated by patients with Crohn's disease with regard to objective signs of neurotoxicity. A few patients from all three groups showed a raised perception threshold for changes of temperature in the feet (as compared with the department's normal standard). The results of the test were almost identical in the three groups and thus not connected with the metronidazole treatment. During the study, patients were asked about subjective neurologic symptoms such as tingling and numbness. A few patients from all three groups reported such paresthesias from time to time, but they were of a transient nature, not perpetual, and, in patients taking metronidazole, not aggravated despite continuing treatment with unchanged dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Effect of lactic acid producing bacteria on the human intestinal microflora during ampicillin treatment.

20 healthy volunteers participated in a double blind study concerning the effect of lactic acid producing bacteria on the intestinal microflora during ampicillin treatment. 10 volunteers received 500 mg ampicillin tablets t.i.d. together with capsules containing lactic acid producing bacteria (Lactobacillus acidophilus and Bifidobacterium bifidum) for 7 days, and the other 10 volunteers were given 500 mg ampicillin tablets together with placebo capsules t.i.d. for 7 days. Both groups of volunteers continued the intake of the capsules t.i.d. for another 14 days after the ampicillin administration had been completed. The number of enterococci, streptococci and corynebacteria decreased during ampicillin administration but returned to normal levels after 14 days. Yeasts increased during the antibiotic treatment but returned to the same levels as before treatment within 14 days. Escherichia coli strains were suppressed in most volunteers during ampicillin administration. The numbers of anaerobic gram-positive cocci and rods decreased in most subjects during ampicillin treatment but were normalized within 2 weeks. Bacteroides strains were recovered in higher numbers in the lactic acid producing bacteria group compared to the placebo group. The volunteers receiving lactic acid producing bacteria were recolonized slightly faster than those having placebo. There were adverse effects observed in 3 subjects receiving ampicillin plus placebo. In the lactic acid producing bacteria group, one subject had diarrhoea on day 3 to on day 3 to day 7.

Adult↗

PubMed1991

Interruption of the enterohepatic circulation of bile acids stimulates the esterification rate of cholesterol in human liver.

The activity of acyl CoA: cholesterol acyltransferase (ACAT), which catalyzes the esterification of cholesterol, was studied in liver microsomes obtained from cholestyramine-treated gallstone patients (n = 12) and patients with Crohn's disease who had undergone partial ileal resection (n = 11). Gallstone patients (n = 33) and gallstone-free subjects undergoing cholecystectomy because of polyps of the gallbladder (n = 8) served as controls. The mean levels of the ACAT activity were the same in the gallstone and the gallstone-free patient groups (6.0 +/- 0.4 and 6.1 +/- 1.1 pmol/min per mg protein, respectively). When exogenous cholesterol was added to the assay system the activities were increased four- to fivefold in both groups. The ACAT activity tended to be increased in the cholestyramine-treated patients (8.1 +/- 1.8 pmol/min per mg protein), and was significantly enhanced (P less than 0.005) in the ileal-resected patients (12.3 +/- 2.3 pmol/min per mg protein). When the enzyme activity was determined with added exogenous cholesterol, it was significantly higher compared to the controls in both the cholestyramine-treated patients and the patients with ileal resection (57.9 +/- 11.6 and 50.0 +/- 10.3 pmol/min per mg protein, respectively). The content of free and esterified cholesterol in liver homogenates and microsomes was not significantly different between the patient groups. We conclude that ACAT activity is increased in patients with interruption of the enterohepatic circulation of bile acids, and speculate that this reflects a stimulated uptake of lipoprotein cholesterol and may indicate that more cholesteryl esters are incorporated into very low density lipoproteins.

Adult↗

PubMed1991

Distribution of cholesterol between vesicles and micelles in human gallbladder bile: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid.

The present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients (n = 23) and gallstone-free subjects (n = 7). Nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy. The vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation, and a clear separation between the two phases was obtained. The vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 A. The proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group (40% +/- 4%) compared with the gallstone-free (28% +/- 3%), ursodeoxycholic acid (28% +/- 3%) and chenodeoxycholic acid (18% +/- 4%) groups. Despite a low cholesterol saturation of bile in the latter three groups (88% +/- 12%, 51% +/- 9% and 65% +/- 5%, respectively), a considerable part of the biliary cholesterol was carried in the vesicular fraction. The cholesterol/phospholipid ratio in the vesicular fraction averaged between 0.49 and 0.58 in the gallstone, gallstone-free and chenodeoxycholic acid groups, whereas the ursodeoxycholic acid group had a significantly lower ratio of 0.24. The nucleation time of bile from the gallstone group was short (2 +/- 1 days) compared with the gallstone-free, chenodeoxycholic acid and ursodeoxycholic acid groups (23 +/- 3, 24 +/- 6 and 14 +/- 3 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism.

Interruption of the enterohepatic circulation of bile acids by cholestyramine or colestipol influences the hepatic metabolism of cholesterol in many ways. The synthesis of bile acids is increased, as reflected by a several-fold increase in the activity of the cholesterol 7 alpha hydroxylase, the rate-determining enzyme in bile acid synthesis. The increased metabolism of cholesterol to bile acids causes an enhanced demand of cholesterol in the hepatocytes which respond with both new synthesis of cholesterol, as reflected in a several-fold increase of the HMG-CoA reductase activity, and increased expression of LDL receptors. As a consequence, the plasma level of LDL-cholesterol is lowered. The hepatic secretion rate of VLDL particles is increased. Cholestyramine therapy does not affect the output of biliary lipids or the cholesterol saturation of bile, indicating that treatment with bile acid sequestrants should not be associated with any increased risk of gallstone formation.

Bile↗

PubMed1991

Hepatic cholesterol metabolism in cholesterol gallstone disease.

Hepatic cholesterol metabolism was examined in 27 Swedish patients with cholesterol gallstone disease and in 13 patients free of gallstones operated for roentgenographically suspect polyps in the gallbladder. All 40 patients underwent cholecystectomy, and a liver biopsy and gallbladder bile were obtained at surgery. The cholesterol saturation of gallbladder bile was significantly higher in patients with gallstones compared to the gallstone-free controls (131 +/- 13 vs. 75 +/- 5%, P less than 0.001). Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, governing cholesterol synthesis, did not differ between gallstone and gallstone-free patients (104 +/- 11 vs. and 109 +/- 22 pmol/min per mg protein, respectively). The activity of cholesterol 7 alpha-hydroxylase, catalyzing the catabolism of cholesterol to bile acids, was not significantly decreased in gallstone patients (6.2 +/- 1.1 vs. 8.0 +/- 2.0 pmol/min per mg protein). The capacity to esterify cholesterol, judged by the activity of acyl coenzyme A:cholesterol acyltransferase (ACAT), was similar in gallstone and gallstone-free patients (5.4 +/- 0.4 vs. 6.7 +/- 1.1 pmol/min per mg protein). In the presence of exogenous cholesterol, ACAT activity increased by more than fourfold in both groups. No correlation was found between the saturation of gallbladder bile and any of the mentioned enzyme activities in gallstone patients. It is concluded that distinct abnormalities in cholesterol metabolizing enzymes are not of major importance for development of gallstones in Swedish patients with cholesterol gallstone disease. The results support the contention that the etiology of cholesterol gallstones is multifactorial.

Adolescent↗

PubMed1990

Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol.

BACKGROUND: Inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, are now used frequently to treat hypercholesterolemia. We studied the effects of specific inhibition of cholesterol synthesis by one of these agents (pravastatin) on the hepatic metabolism of cholesterol in patients with gallstone disease who were scheduled to undergo cholecystectomy. METHODS: Ten patients were treated with pravastatin (20 mg twice a day) for three weeks before cholecystectomy; 20 patients not treated served as controls. A liver specimen was obtained from each patient at operation, and the activities of rate-determining enzymes in cholesterol metabolism as well as low-density-lipoprotein (LDL)-receptor binding activity were determined. RESULTS: Pravastatin therapy reduced plasma total cholesterol by 26 percent and LDL cholesterol by 39 percent (P less than 0.005). Serum levels of free lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, decreased by 63 percent (P less than 0.005), indicating reduced de novo biosynthesis of cholesterol. Microsomal HMG-CoA reductase activity, when analyzed in vitro in the absence of the inhibitor, was increased 11.8-fold (1344 +/- 311 vs. 105 +/- 14 pmol per minute per milligram of protein in the controls; P less than 0.001). The expression of LDL receptors was increased by 180 percent (P less than 0.005), whereas the activities of cholesterol 7 alpha-hydroxylase (which governs bile acid synthesis) and of acyl-coenzyme A:cholesterol O-acyltransferase (which regulates cholesterol esterification) were unaffected by treatment. CONCLUSIONS: Inhibition of hepatic HMG-CoA reductase by pravastatin results in an increased expression of hepatic LDL receptors, which explains the lowered plasma levels of LDL cholesterol.

Aged↗

PubMed1990

Characteristics of biliary lipid metabolism after liver transplantation.

Biliary lipid metabolism was studied after 10 liver transplantations with continuous drainage of bile. Within 3 wk after transplantation, the new liver produced bile with concentrations of biliary lipids in agreement with those reported for T-tube bile in cholecystectolized nontransplanted subjects. Although changes in biliary lipid composition occurred swiftly in response to various forms of disturbed liver function, they did not provide substantially more information than did standard serum tests or simple measurements of bile flow in most patients. Secretion rates of phospholipids and cholesterol were found to be completely bile acid dependent. For each micromole of bile acids, 0.22 and 0.08 mumol of phospholipids and cholesterol were secreted, respectively. When bile flow was related to bile acid output, a linear relationship was found (r = 0.89), with a positive intercept indicating a bile acid-independent bile flow of approximately 44 microliters/min. Analysis of individual bile acids showed almost exclusively primary bile acids. The relative proportion of chenodeoxycholic acid was more prominent during the first days after transplantation. Different explanations for this are discussed.

Adult↗

PubMed1990

Low density lipoprotein receptor-binding activity in human tissues: quantitative importance of hepatic receptors and evidence for regulation of their expression in vivo.

The heparin-sensitive binding of 125I-labeled low-density lipoprotein (LDL) to homogenates from 18 different normal human tissues and some solid tumors was determined. The binding to adrenal and liver homogenates fulfilled criteria established for the binding of LDL to its receptor--namely, (i) saturability, (ii) sensitivity to proteolytic destruction, (iii) inhibition by EDTA, and (iv) heat sensitivity. When the binding of 125I-labeled LDL was assayed at a constant concentration (50 micrograms/ml), the adrenal gland and the ovary had the highest binding of normal tissues. The highest binding per g of tissue overall was obtained in homogenates of a gastric carcinoma and a parotid adenoma. When the weights of the parenchymatous organs were considered, the major amount of LDL receptors was contained in the liver. To study the possible regulation of hepatic LDL-receptor expression, 11 patients were pretreated with cholestyramine (8 g twice a day for 3 weeks). Increased binding activity (+105%, P less than 0.001) was obtained in homogenates from liver biopsies from the cholestyramine-treated patients as compared with 12 untreated controls. It is concluded that the liver is the most important organ for LDL catabolism in humans and that the receptor activity in this organ can be regulated upon pharmacologic intervention. Further studies are needed to confirm the possibility that certain solid tumors can exhibit high numbers of LDL receptors.

Adrenal Cortex↗

PubMed1990

Bile acid metabolism in familial dysbetalipoproteinaemia: studies in subjects with the apolipoprotein E-2/2 phenotype.

Bile acid kinetics and biliary lipid composition were determined in seven subjects with primary dysbetalipoproteinaemia. They were all homozygous for the apolipoprotein E isoform E-2 and six of them were hyperlipidaemic (type III hyperlipoproteinaemia). With or without hyperlipidaemia, the apo E-2/2 phenotype was associated with increased bile acid formation (mean increase compared with 32 normolipidaemic controls, 43%; P less than 0.025). The biliary lipid composition was not different from that seen in the controls. The results indicate that the uptake by the liver of apo E-containing remnant particles is of importance for the regulation of hepatic cholesterol metabolism in man. It is suggested that hepatic cholesterol synthesis is stimulated in dysbetalipoproteinaemia, and that this leads to a compensatory increase in bile acid synthesis.

Adult↗