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Biomedical subjects

B Angelin

Publications and source records attributed to B Angelin.

At least 235 records · Page 13Linked to original sources
PubMed1980

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↗
PubMed1980

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↗
PubMed1979

Adrenal hydroxylations in genetically obese and hypertensive rats.

The separate steps in the formation of aldosterone from cholesterol were studied in a strain of spontaneously hypertensive rats in which phenotypic obesity is inherited as a recessive trait (Koletsky rats). The obese and hypertensive state had little or no effect on side-chain cleavage of cholesterol, formation of progesterone from pregnenolone or 21-hydroxylation. Mitochondrial 18-hydroxylation of endogenous and exogenous corticosterone, however, as well as 18- and 11 beta-hydroxylation of deoxycorticosterone, were increased in obese hypertensive rats, both when compared with non-obese hypertensive siblings and when compared with healthy Sprague-Dawley rats. 18-Hydroxylation of corticosterone was increased more than 18-hydroxylation of deoxycorticosterone. In non-obese hypertensive rats, the adrenal content of mitochondrial cytochrome P-450 was lower than that in obese hypertensive rats but higher than that in rats of the conventional Sprague-Dawley strain. The results are discussed with respect to possible heterogeneity of adrenal cytochrome P-450 and to possible explanations for the changes observed.

Adrenal Glands↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

Decreased nitroblue tetrazolium reduction of granulocytes in type IV hyperlipoproteinemia.

NBT reduction of granulocytes was determined in 40 patients with primary hyperlipoproteinemia. The reaction was measured in granulocytes both in the resting state and after stimulation with E. coli, as well as with and without addition of plasma. In 17 patients with type IV hyperlipoproteinemia (endogenous hypertriglyceridemia), the NBT reduction was significantly decreased in all these types of experiments when compared with 12 healthy controls. Sera from hypertriglyceridemic patients decreased NBT reduction of normal granulocytes. Increasing concentration of VLDLs from normolipidemic donors had the same effect. It is suggested that plasma lipoproteins may influence granulocyte function.

Cell Membrane Permeability↗
PubMed1979

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↗
PubMed1978

Effect of cholestyramine on bile acid kinetics in patients with portal cirrhosis of the liver. Evidence of a selective defect in the formation of cholic acid.

The kinetics of cholic acid (C) and chenodeoxycholic acid (CD) were studied in six patients with portal liver cirrhosis. The studies were conducted both before and after 5-6 weeks of treatment with cholestyramine (12 g/day). In keeping with previous observations, the pool size and formation of C showed subnormal values during the pretreatment period, while the production of CD was within normal limits. The pool sizes of C and CD did not change upon treatment with cholestyramine, but the mean total bile acid formation increased by a factor of about 2.5. The ratio between the amounts of C and CD synthesized remained essentially unchanged. Considering the therapeutic response previously observed in normal subjects and in patients with hyper-beta-lipoproteinemia, the present results suggest a selective impairment of the biosynthesis of C in patients with portal liver cirrhosis. It is suggested that the primary defect may reside in the 12alpha-hydroxylase enzyme system.

Aged↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

Individual serum bile acid concentrations in normo- and hyperlipoproteinemia as determined by mass fragmentography: relation to bile acid pool size.

Combined gas-liquid chromatography-mass spectrometry with specific ion monitoring (mass fragmentography) has been used for assay of cholic acic (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) in human serum. Deuterium-labeled C and D were used as internal standards. The relative standard deviation of duplicate samples was 3, 4, and 7% for C, CD, and D, respectively. The variation within the same individual in the fasting state was small, while the day-to-day variation was greater, especially for the dihydroxy bile acids. In normal control subjects (n = 24), the fasting serum concentration of C averaged 184 +/- 24 ng/ml (mean +/- SEM), and that of CD and D 526 +/- 62 and 407 +/- 44 ng/ml, respectively. Patients with type IIa hyperlipoproteinemia (n = 32) displayed low values of serum bile acids, with a C concentration of 121 +/- 11 ng/ml (P less than 0.01 vs. controls). A similar pattern was seen in patients with a type IIb lipoprotein pattern (n = 10). Subjects with type IV hyperlipoproteinemia (n = 32) showed serum bile acid levels within the normal limits. No relationship to age, sex, or body weight was seen in any of the patient subgroups. Bile acid kinetics were determined with an isotope dilution technique using 14C-labeled C and CD under steady state conditions in control subjects and patients with type IIa and type IV hyperlipoproteinemia. The serum concentration of C correlated significantly to its pool size in control subjects and in patients with type IIa hyperlipoproteinemia but not in patients with type IV. The serum level of CD was not related to CD pool size in any of the subgroups. The data obtained are discussed in relation to present concepts of the enterohepatic circulation. It is suggested that the intestinal content of C in the fasting state is proportional to the total C pool size. The possibility of a defective intestinal uptake of C in some patients with type IV hyperlipoproteinemia is raised.

Bile Acids and Salts↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

Influence of cholestyramine on synthesis of cholesterol and bile acids in germfree rats.

The present investigation describes the influence of partial, pharmacologic interruption of bile acid enterohepatic circulation on cholesterol and bile acid synthesis in germfree rats. Seven rats received a basal, semisynthetic diet and five rats received the basal diet supplemented with 5% cholestyramine. After 6 weeks, feces were collected in one 3- and one 4-day pool for analysis of bile acids and cholesterol. When the sampling period was concluded, the rats were killed and the liver microsomal fractions were isolated. The activities of HMG CoA reductase and 7alpha-hydroxylase were determined. The main fecal bile acids in the untreated rats were cholic acid and beta-muricholic acid. During cholestyramine treatment cholic acid increased from 4.4 +/- 0.7 to 39.5 +/- 5.6 mg/kg body weight/day and beta-muricholic acid from 4.5 +/- 0.6 to 7.7 +/- 0.9 mg/kg body weight/day. Chenodeoxycholic acid became a major bile acid averaging 10.4 +/- 1.6 mg/kg body weight/day. The total amount of bile acids increased about 6-7 times and the percentage of cholic acid increased from 49.4 +/- 2.0 to 68.6 +/- 1.1%. The 7alpha-hydroxylase activity increased 4-5 times. During cholestyramine treatment the fecal excretion of cholesterol was increased from 12.0 +/- 1.4 to 68.0 +/- 5.0 mg/kg body weight/day. The endogenous formation of cholesterol was increased 6 times and the HMG CoA reductase activity was increased about 20 times. In conclusion, germfree rats, like conventional rats, have the ability to increase the endogenous formation of bile acids and cholesterol during interruption of the enterohepatic circulation of bile acids, which is also reflected in a stimulation of the activities of the rate-determining enzymes.

Animals↗