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Biomedical subjects

K Einarsson

Publications and source records attributed to K Einarsson.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1977

Serum lipids before and after parathyroidectomy in patients with primary hyperparathyroidism.

Eight males and 36 females with hypercalcaemia were operated upon for primary hyperparathyroidism and parathyroid adenomata were revealed in every case. The serum levels of cholesterol and triglycerides were determined before the operations and 6,12 and 18 months after them. Furthermore, the serum lipids of the patients were compared with those of a normacalcaemic sex- and age-matched control group. The serum cholesterol concentration in primary hyperparathyroidism was about 8-10% lower in both females and males compared with the correspondeing control cases and the levels of serum trigycerides were about 22% and 60% lower. After operation the serum cholesterol concentration returned to a normal level and the triglycerides nomalized. The results are discussed in the light of present knowledge about dietary calcium intake, primary hyperparathyroidism and lipid metabolism.

Adenoma↗
PubMed1977

Cholelithiasis in subjects with hypercalcaemia and primary hyperparathyroidism detected in a health screening.

The frequency of gallstone disease was studied in a group of 82 subjects (69 females and 13 males; mean ages 55-0 and 52-3 years, respectively) with verified hypercalcaemia (VHC) detected in a health screening in the Stockholm area. All non-cholecystectomised subjects were examined with a peroral cholecystography. Causes of hypercalcaemia other than primary hyperparathyroidism (PHPT) had been excluded as far as possible. Sixty-two patients had been operated upon and all but two males were found to have parathyroid adenomas. The patients were compared with a series of 82 normocalcaemic age- and sex-matched subjects, selected from the health screening register. The patients with VHC and/or PHPT had about the same frequency of gallstone disease as the controls. The results are at variance with those of other investigators who have reported that PHPT is associated with an abnormally high frequency of gallstone disease. Possible explanations of the discrepancy in results is discussed.

Cholelithiasis↗
PubMed1977

Individual bile acids in portal venous and systemic blood serum of fasting man.

The serum concentrations of cholic acid (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) were determined in peripheral venous and portal venous blood from 10 otherwise healthy patients undergoing elective cholecystectomy. A highly specific and accurate gas chromatographic-mass spectrometric technique was used. Peripheral venous serum contained 0.49 +/- 0.16 (mean +/- SEM) mumole per liter of C, 1.55 +/- 0.32 mumoles per liter of CD, and 1.44 +/- 0.57 mumoles per liter of D. Arterial serum, obtained from 5 of the subjects, did not show any differences in bile acid concentrations compared to venous serum. In contrast, the portal venous content of each bile acid was several-fold greater, 6.14 +/- 1.20 mumoles per liter of C, 8.40 +/- 1.84 mumoles per liter of CD, and 6.18 +/- 2.27 mumoles per liter of D. The hepatic uptake of C was estimated to be about 90%, whereas that of CD and D was lower, about 70%. This difference in hepatic uptake between the individual bile acids was reflected in the relative composition of the total bile acids, which was 30:39:31 (C:CD:D) in portal venous serum and 13:50:37 in peripheral serum. Compared to common duct bile obtained simultaneously, the portal vein contained a greater proportion of CD. The relevance of the data obtained to our present concept of the enterohepatic circulation of bile acids is discussed, and it is suggested that the higher fasting level of CD compared to C in peripheral serum results from the combination of a lower fractional hepatic extraction and a higher portal venous input to the systemic circulation.

Aged↗
PubMed1977

Effects of cholesterol feeding on synthesis and metabolism of cholesterol and bile acids in germfree rats.

The aim of the present investigation was to study the influence of cholesterol feeding on cholesterol synthesis and fecal excretion of bile acids in germfree rats. Four germfree rats were fed a basal diet containing 0.004% cholesterol and four germfree rats received the same diet supplemented with 0.4% cholesterol for 2 weeks. Cholesterol synthesis was studied by assaying the HMG CoA reductase activity in the liver microsomal fraction. Cholesterol feeding decreased the HMG CoA reductase activity from 28.5 +/- 6.6 (mean +/- SEM) to 9.1 +/- 0.7 pmol/mg protein per min. In another experiment four germfree rats received the basal diet and four germfree rats the cholesterol-enriched diet. After 6 weeks feces were collected in two 4-day pools for analysis of bile acids. The main fecal bile acids were cholic acid and beta-muricholic acid (a metabolite of chenodeoxycholic acid), comprising more than 95% of total bile acids. Cholic acid was increased from 3.9 +/- 0.2 to 9.9 +/- 1.2 mg/kg body weight per day and beta-muricholic acid from 6.6 +/- 0.5 to 21.8 +/- 3.1 mg/kg body weight per day. The percentage of cholic acid decreased from 37.1 +/- 1.1 to 31.2 +/- 1.0%. In conclusion, germfree rats like conventional rats have the ability to compensate for an increased input of dietary cholesterol by inhibition of cholesterol synthesis and stimulation of bile acid synthesis. The synthesis of chenodeoxycholic acid (implied from the fecal excretion of beta-muricholic acid) is stimulated to a greater extent than that of cholic acid.

Animals↗
PubMed1976

The metabolism of steroids in the fatty liver induced by orotic acid feeding.

1. The metabolism of 4-[4-14C]androstene-3,17-dione, 4-[4-14C]pregnene-3,20-dione, 5alpha-[4-14C]androstane-3alpha,17beta-diol, [4-14C]cholesterol, 7alpha-hydroxy-4-[6beta-3H]cholesten-3-one, 5beta-[7beta-3H]cholestane-3alpha,7alpha-diol and [3H]lithocholic acid was studied in the microsomal fraction of livers from control and orotic acid-treated male rats. 2. As a result of the treatment the orotic acid-fed rats had fatty livers and subnormal concentrations of cholesterol and triglycerides in serum. 3. The 6beta- and 7alpha-hydroxylation of 4-androstene3,17-dione, and the 2alpha-, 2beta- and 18-hydroxylation of 5alpha-androstane-3alpha,17beta-diol, and the 5alpha-reduction of 4-androstene-3,17-dione and 4-pregnene-3,20-dione were decreased by 40--50% in orotic acid-fed rats. Other oxidative and reductive reactions of the steroid hormones were not significantly affected. 4. The 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one was decreased by about 50%, whereas the 7alpha-hydroxylation of cholesterol and the 26-hydroxylation of 5beta-cholestane-3alpha,7alpha-diol were not significantly decreased. The 6beta-hydroxylation of lithocholic acid was stimulated by 40%. 5. The results are discussed in relation to present knowledge of the heapatic drug-metabolizing enzymes and to the recent findings of an abnormal bile acid metabolism in liver disease.

Androstane-3,17-diol↗
PubMed1976

Effects of clofibrate on some microsomal hydroxylations involved in the formation and metabolism of bile acids in rat liver.

1. The liver microsomal metabolism of [4-14C]cholesterol, endogenous cholesterol, 7 alpha-hydroxy-4-[6 beta-3H]cholesten-3-one, 5-beta-[7 beta-3H]cholestane-3 alpha, 7 alpha-diol and [3H]lithocholic acid was studdied in control and clofibrate (ethyl p-chlorophenoxyisobutyrate)-treated rats. 2. The extent of 7 alpha-hydroxylation of exogenous [414C]cholesterol and endogenous cholesterol, the latter determined with a mass fragmentographic technique, was the same in the two groups of rats. The extent of 12 alpha-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one and 5 beta-cholestane-3 alpha, 7 alpha-diol was increased by about 60 and 120% respectively by clofibrate treatment. The 26-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha-diol was not significantly affected by clofibrate. The 6 beta-hydroxylation of lithocholic acid was about 80% higher in the clofibrate-treated animals than in the controls. 3. The results are discussed in the context of present knowledge about the liver microsomal hydroxylating system and bile acid formation in patients with hypercholesterolaemia, treated with clofibrate.

Animals↗
PubMed1976

Elimination of cholesterol in hyperlipoproteinaemia.

1. Cholesterol intake (about 0-25 mmol/day) and the faecal excretion of cholesterol, coprostanol and coprostanone were determined in normolipidaemic control subjects and hyperlipidaemic patients, whose bile acid kinetics had been previously studied. 2. The combined excretion of the neutral steroids (excluding plant sterol and plant sterol metabolites) averaged 1-07 +/- 0-13 (+/-SEM)mmol/day in the control subjects (n=14). The corresponding values in patients with hyperlipoproteinaemia type IIa (n=19), IIb (n=12) and IV (n=23) were 0-86 +/- 0-10, 0-93 +/- 0-11 and 1-48 +/- 0-17 mmol/day respectively. 3. The mean values for the net steroid "balance", defined as the combined amount of bile acid synthesized (determined by an isotope-dilution technique) and the faecal excretion of neutral steroids minus cholesterol intake, were 1-83 +/- 0-22 mmol/day in the control subjects and 1-60 +/- 0-15, 1-81 +/- 0-19 and 3-53 +/- 0-23 mmol/day in patients with type IIa, IIb and IV lipoprotein patterns respectively. 4. No significant correlations between net steroid "balance" and sex, age, serum lipid concentrations, body weight or body surface area were found in any of the groups of subjects. 5. It is concluded that patients with type II hyperlipoproteinaemia eliminate cholesterol as bile acids and neutral faecal steroids normally. The type IV lipoprotein pattern is associated with increased bile acid synthesis and/or elevated faecal excretion of neutral steroids, so that the net steroid "balance" is usually above the normal limit.

Bile Acids and Salts↗
PubMed1976

Influence of fructose feeding on individual enzymic reactions in the formation and metabolism of bile acids in rat liver homogenates.

1. Rats were maintained for 10 d on a semi-synthetic diet containing 700 g glucose or 700 g fructose/kg. Individual enzymic reactions in bile acid synthesis and metabolism were studied by measuring the 7alpha-hydroxylation of [4-14C]cholesterol, and 12alpha-hydroxylation of 7alpha-[6beta-3H]hydroxy-4-cholesten-3-one, the 26-hydroxylation of 5beta-[7beta-3H]cholestane-3alpha,7alpha-diol and the 6beta-hydroxylation of [3H]lithocholic acid in liver homogenates. 2. The serum cholesterol level was approximately the same in both groups of animals, but the serum triglyceride level was almost twice as high in the fructose-fed rats compared to the glucose-fed rats. 3. The 6beta-hydroxylation of [3H]ithocholic acid was increased by about 20% in the fructose-fed rats compared to the glucose-fed animals. The activities of the other enzymic reactions studied did not differ significantly between the two groups of animals. The findings are discussed in relation to previous knowledge concerning mechanisms regulating triglyceride, pre-beta-lipoprotein and bile acid synthesis.

Animals↗
PubMed1976

Evidence for the absorption of bile acids in the proximal small intestine of normo- and hyperlipidaemic subjects.

Bile acid composition was determined in duodenal and jejunal aspirates obtained under fasting conditions in normolipidaemic controls and in patients with the type IIa and type IV lipoprotein patterns. In 17 out of the 22 subjects studied, the duodenal as compared with the jejunal aspirates contained proportionally more CD (chenodeoxycholic acid) than C (cholic acid). The two types of aspirates also differed slightly with regard to the D (deoxycholic acid): CD ratio, which was higher in samples drawn from the jejunum. These findings, compatible with an absorpiton of about 30% of CD in the upper small intestine, were approximately the same in all groups of patients. As evidenced by additional experiments in two subjects, an oral intake of cream does not significantly influence the absorption of CD in the upper small intestine.

Bile Acids and Salts↗