PubMed Health⌕ Search

Biomedical subjects

B Leijd

Publications and source records attributed to B Leijd.

At least 37 records · Page 2Linked to original sources

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↗

Cholesterol and bile acid metabolism in obesity.

1. The present study was undertaken to determine the influence of obesity on bile acid kinetics and cholesterol balance in man. 2. Fourteen obese and normolipidaemic patients (160 +/- 6% of ideal body weight, mean +/- SEM) were studied under standardized dietary conditions. Bile acid kinetics, were determined with the aid of 14C-labelled cholic acid and chenodeoxycholic acid. Cholesterol balance was calculated as the sum of bile acid synthesis plus daily faecal excretion of neutral C27 steroids minus dietary intake of cholesterol. The results obtained were compared with previously published data on control subjects (n = 13). 3. The cholesterol balance was higher in the obese patients (2.61 +/- 0.27 mmol/day) than in the control subjects (1.78 +/- 0.22 mmol/day), owing to a higher excretion of neutral steroids. When expressed per kg of body weight the cholesterol balance was quite normal in the obese patients.

Chenodeoxycholic Acid↗

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↗

Effects of cholic acid on the metabolism of endogenous plasma triglyceride and on biliary lipid composition in hyperlipoproteinemia.

Plasma lipids, endogenous triglyceride kinetics, and biliary lipid composition were determined in 13 patients with primary hyperlipoproteinemia (HLP) before and during treatment with cholic acid (15 mg/kg body weight/day for 3 months). In patients with type IIa HLP (n = 5), no consistent effects were seen on fasting plasma lipids or triglyceride turnover determined over a 10-hour period. Plasma triglyceride concentration was decreased in six of the eight patients with type IV HLP. Apparent triglyceride production rate was not significantly changed with initially elevated triglyceride synthesis. Treatment with cholic acid resulted in an increased proportion of bile acids and a decreased proportion of cholesterol and phospholipids in fasting duodenal bile; bile saturation with cholesterol was not significantly reduced. The results ,re discussed in relation to previous studies on the integrated regulation of bile acid and triglyceride metabolism, and it is concluded that cholic acid and chenodeoxycholic acid exert different effects on plasma triglyceride metabolism and on biliary lipid composition in HLP.

Adult↗

Biliary lipid composition in normo- and hyperlipoproteinemia.

The lipid composition of fasting gallbladder bile obtained under standardized conditions was determined in healthy controls and in patients with hyperlipoproteinemia without gallstones. Altogether 23 normolipidemic controls (10 males and 13 females) and 50 hyperlipidemic patients (31 type IIa, 7 type IIb, and 12 type IV) were studied; all were less than 15% overweight. The cholesterol saturation averaged 96 +/- 5% (mean +/- SEM) in the controls, and 10 of them had bile supersaturated with cholesterol. There was no difference between males and females. An increased saturation with age was seen in females. A normal biliary cholesterol saturation (102 +/- 3%) was found in patients with hyperlipoproteinemia type IIa; this was true also for the subgroup with established familial hypercholesterolemia. All patients with hyperlipoproteinemia type IIb and 10 of those with type IV had saturated bile (135 +/- 8% and 121 +/- 6%, respectively). The results suggest an association between certain forms of hyperlipoproteinemia and the development of supersaturated bile. Since fasting gallbladder bile supersaturated with cholesterol is considered to precede gallstone formation, the present results may explain previous findings of an increased prevalence of gallstone disease in patients with hypertriglyceridemia.

Age Factors↗

Prevalence of gallbladder disease in hyperlipoproteinemia.

An analysis of the occurrence of gallbladder disease (ie, cholelithiasis, cholecystitis, cholecystectomy) in 210 consecutive patients with primary hyperlipoproteinemia showed that the prevalence of gallbladder disease was 8%, 18%, and 42% in males with type IIa, IIb, and IV hyperlipoproteinemia, and 22%, 48%, and 72% in the corresponding groups of females. The 40-59-year-old patients were compared to three necropsy series from Malmö, Sweden. The occurrence of gallbladder disease was within normal limits in type IIa and abnormally high in type IV hyperlipoproteinemia. There were no differences with regard to age, body weight, glucose intolerance, or ischemic heart disease between type IV patients with and without GBD. It is suggested that certain forms of disturbances of lipoprotein metabolism are associated with an increased risk for development of gallbladder disease.

Adult↗

Biliary lipid composition during treatment with different hypolipidaemic drugs.

In an attempt to clarify the possible lithogenic effects of commonly used hypolipidaemic drugs, gallbladder bile was obtained from patients with primary hyperlipoproteinaemia before and during treatment with nicotinic acid (n = 13), cholestyramine (n = 19), clofibrate (n = 11), and a combination of cholestyramine and clofibrate (n = 11). Each treatment period was minimum 6 weeks, and standardized dietary conditions were obtained. Both nicotinic acid and clofibrate treatment caused an increase in biliary cholesterol concentration relative to biliary total lipids (bile acids, phospholipids, and cholesterol). During cholestyramine medication the relative cholesterol concentration fell. A combination of cholestyramine with clofibrate medication led to a decrease of bile saturation to pretreatment levels in nine of the eleven subjects. In the other two a further increase in the cholesterol saturation of the bile occurred. Treatment with nicotinic acid and clofibrate but not with cholestyramine is thus probably associated with an increased risk for development of cholesterol gallstones. It is suggested that addition of cholestyramine may be a possible way to prevent the lithogenic effect of clofibrate in patients with hyperlipoproteinaemia when not only hypocholesterolaemic but also hypotriglyceridaemic effects are wanted.

Adult↗

Hepatic cholesterol metabolism in normo- and hyperlipidemic patients with cholesterol gallstones.

In vivo studies have shown abnormalities in cholesterol and bile acid metabolism in primary hyperlipoproteinemia (HLP). The aim of the present investigation was to determine if the increased production of cholesterol in HLP type IV can be attributed to a correspondingly high level of the hepatic 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity and if the low cholic acid: chenodeoxycholic acid synthesis ratio in HLP type II is due to some hydroxylase deficiency. Liver biopsies from 26 normolipidemic and 25 hyperlipidemic (10 type IIa, 6 type IIb, and 9 type IV) patients undergoing elective cholecystectomy were assayed for HMG CoA reductase activity, 12 alpha-hydroxylase activity, and 25-hydroxylase activity. The HMG CoA reductase activity was normal in HLP type IIa and type IIb and was increased about twice HLP type IV (P less than 0.001). The 12 alpha- and 25-hydroxylase activities were normal in all groups of patients. The results are compatible with a normal cholesterol synthesis in the liver in HLP type II. A reduced 12 alpha- or 25-hydroxylase activity cannot explain the low production of cholic acid relative to chenodeoxycholic acid in this type of HLP. The elevated HMG CoA reductase activity found in the liver of type IV patients may, however, be part of the explanation for the elevated synthesis of cholesterol often seen in these patients.

Adult↗

Effect of chenodeoxycholic acid on serum and biliary lipids in patients with hyperlipoproteinaemia.

1. In order to study the effects of chenodeoxycholic acid on serum and biliary lipids in hyperlipoproteinaemia, chenodeoxycholic acid was administered to seven type IIa, eight type IIb and eight type IV patients in a daily dose of 750 mg (1.9 mmol) for 3 months. 2. The serum concentrations of cholesterol and triglycerides were determined at 4-week intervals: cholesterol remained unchanged whereas triglycerides decreased 15--20%. 3. In 17 patients, biliary lipids were studied. The proportion of chenodeoxycholic acid in the bile increased to about 70%; lithocholic acid and ursodeoxycholic acid increased significantly. 4. Bile saturation with cholesterol decreased and correlated negatively with the proportion of chenodeoxycholic acid in biliary bile acids but positively with serum triglycerides. 5. It is concluded that chenodeoxycholic acid treatment in hyperlipoproteinaemia is associated with parallel fall in serum triglycerides and biliary cholesterol and thus may prove to be a useful adjunct in hypolipidaemic treatment.

Bile↗

Intracutaneous herniation of fat in connection with microangiopathia diabetica.

Three women with diabetes mellitus presented an unusual change in the skin on the distal and acral parts of the extremities, most distinctly on the upper surface of the hands. The surface was raised in small cushions but had the colour of intact skin. The skin felt doughy and swolen on palpation but there was no oedematous pitting. It had been suspected earlier that these skin changes indicated myxoedema or heart disease and the patients had been treated with diuretics. In all three cases, however, histological examinations revealed a more or less reduced, atrophic dermis with here and there an appreciable dislocation of the subcutaneous layer of fat, which with the sweat glands formed an intracutaneous herniation up against the epidermis. These histological changes explained the clinical picture of cushions in the skin. As these patients had diabetes mellitus and the histological picture also included vascular changes of the type associated with a diabetic microangiopathy, it is considered that this form of intradermal herniation of fat is yet another skin change which may be elicited by diabetes mellitis.

Adipose Tissue↗

Hypocalcaemia with zonular cataract due to idiopathic hypoparathyroidism. With a note on the prevalence of severe hypocalcaemia in a health screening.

A 59-year-old woman with idiopathic hypoparathyroidism who had tetany and zonular cataract is described. Twelve years ago she had had a period with cramps and convulsions, followed by an absence of symptoms for several years. Judging from the distance between the opacity of cataract and the surface of the lens, the onset of the cataract was estimated to have occurred 11 years ago and the apparent cessation of cataract development 10 years ago. It is suggested that the absence of hypocalcaemic symptoms during the last 10 years was associated with an increase in serum calcium levels, possibly connected with the onset of menopause. The occurrence of hypocalcaemia was analyzed in a health-screened population of 15 903 persons. Nine of the subjects were found to have a serum calcium level of less than 2.10 mmol/l, giving a prevalence of 0.6%0. None had primary hypoparathyroidism, which illustrates the rarity of this condition.

Cataract↗

Bile acid kinetics in relation to endogenous tryglyceride metabolism in various types of hyperlipoproteinemia.

Bile acid and plasma endogenous triglyceride kinetics were determined under standardized dietary conditions in 47 hyperlipidemic subjects with the aid of [14C]cholic acid, [14C]chenodeoxycholic acid, and [3H]glycerol, respectively. On the basis of their lipoprotein pattern the patients were separated into three groups characterized by hyperlipoproteinemia (HLP) type IIa (n = 19), type IIb (n = 6), and type IV (n = 22). In keeping with previous reports from this laboratory the total bile acid formation reports from this laboratory the total bile acid formation in HLP type IV (19.5 +/- 2.2) mumol kg-1d-1, mean +/- SEM) exceeded that encountered in type IIa (10.7 +/- 0.9 mumol kg-1d-1, P less than 0.005). This difference was mainly due to an increased synthesis of cholic acid in type IV HLP (12.7 +/- 1.7 mumol kg-1d-1 vs. 6.1 +/- 0.5 mumol kg-1d-1, P less than 0.005). Bile acid formation in type IIb HLP was essentially within the limits recorded for type IIa. Apparent plasma triglyceride formation (as calculated from the 10-hr radioactivity decay curve) averaged 10.5 +/- 0.7 mumol kg-1hr-1 in type IIa HLP and was significantly higher in type IIb (20.7 +/- 1.9 mumol kg-1hr-1, P less than 0.001) and in type IV (22.1 +/- 1.4 mumol kg-1hr-1, P less than 0.001). The apparent fractional turnover rate of plasma triglyceride in type IV HLP (0.147 +/- 0.011 hr-1) was lower than that encountered in type IIa (0.188 +/- 0.008, P less than 0.01) and in type IIb (0.177 +/- 0.011 hr-1). The apparent production of plasma triglycerides and the formation of cholic acid correlated in type IIa (r = +0.69, P less than 0.001) and in type IV HLP (r = +0.70, P less than 0.001). A similar pattern was seen for total bile acid formation, while chenodeoxycholic acid showed a correlation to apparent triglyceride synthesis only in type IV HLP. It is suggested that an increased formation of plasma triglycerides--monitoring very low density lipoprotein synthesis--is linked to an enhanced degradation of cholesterol to bile acids and that there is an integrated regulation of the metabolism of these two parameters.

Adult↗

Effects of cholestyramine and chenodeoxycholic acid on the metabolism of endogenous triglyceride in hyperlipoproteinemia.

Previous studies conducted under basal conditions have suggested a linkage between the formation of plasma triglyceride and the degradation of cholesterol to bile acids. To further examine this relationship, plasma endogenous triglyceride kinetics were determined using [(3)H]glycerol in 26 hyperlipidemic subjects before and during stimulated (cholestyramine treatment) and inhibited (chenodeoxycholic acid treatment) bile acid synthesis. All patients with hyperlipoproteinemia (HLP) type II (n = 9) treated with cholestyramine (12 g daily for 2-4 months) displayed increased apparent biosynthesis (12.8 +/- 1.5 vs. 9.7 +/- 1.2 micro mol kg(-1)hr(-1), mean +/- SEM, P < 0.005) and an elevated apparent fractional turnover rate (0.230 +/- 0.017 vs. 0.176 +/- 0.014 hr(-1), P < 0.001) as determined over a 10-hr period, in spite of essentially unchanged plasma triglyceride concentrations. No consistent effect of this therapy was encountered in the five patients studied with type IV HLP. Chenodeoxycholic acid feeding (1.9 mmol daily for 3-4 months) resulted in a reduced apparent synthesis of plasma triglycerides both in type IIa (n = 5, 7.9 +/- 0.5 vs. 13.1 +/- 1.2 micro mol kg(-1)hr(-1), P < 0.01) and type IV HLP (n = 7, 15.5 +/- 1.8 vs. 23.6 +/- 3.7 micro mol kg(-1)hr(-1), P < 0.02). Furthermore, a 20-25% reduction of the apparent fractional turnover rate was seen, and the plasma concentration of triglycerides was reduced by about 15%. It is concluded that the present experimental conditions that primarily influence cholesterol and bile acid biosynthesis also affect the metabolism of plasma triglycerides-and presumably that of very low density lipoprotein-in a regulatory manner. Hypothetically, this may be achieved via a hepatic pool of newly synthesized cholesterol.

Adult↗