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Biomedical subjects

B Angelin

Publications and source records attributed to B Angelin.

At least 163 records · Page 9Linked to original sources
PubMed1989

Hypocholesterolaemia and increased elimination of low-density lipoproteins in metastatic cancer of the prostate.

To study the influence of tumour mass on lipid metabolism, the lipoprotein pattern in untreated patients with newly diagnosed cancer of the prostate was examined. Total cholesterol levels were reduced in patients with evidence of metastasis (n = 30) compared with those without metastasis (n = 73). Since the major fraction of serum cholesterol is contained in low-density lipoproteins (LDL), turnover of LDL was studied in detail in 8 patients compared with 12 age-matched healthy men. LDL were cleared faster in the 3 patients with metastatic disease than in the patients without metastasis and in controls, indicating faster catabolism of LDL. Thus in prostatic cancer an increased tumour burden is associated with increased elimination of LDL, which contributes to reduced serum cholesterol levels.

Aged↗
PubMed1989

Tin-protoporphyrin and long wave length ultraviolet light in treatment of psoriasis.

To assess the effects of tin (Sn)-protoporphyrin (a synthetic haem analogue) in conjunction with long wave length ultraviolet light (UVA) radiation in psoriasis 10 patients, 9 of whom were substantially or completely unresponsive to other forms of therapy, received 2.0 mumol/kg bodyweight of Sn-protoporphyrin for 1 day followed by UVA light treatment for 21 days. The average starting UVA dose was 5.6 (SD 2.0) J/cm2, and the average cumulative UVA dose was 98.3 (35.1) J/cm2. Severity of psoriatic plaques, scored clinically on a scale of 0-3 for erythema, scaling, and induration, fell from a mean score of 7.9 at the start of the study to 3.6 at the end. Psoriatic lesions were improved in all patients and the effect was striking in some. The responses lasted throughout the three weeks of the study and no deleterious side-effects of the treatment were noted. Clinical follow-up for three months showed no rebound in disease activity. Sn-protoporphyrin with conventional UVA light may be useful in the treatment of psoriasis.

Adult↗
PubMed1989

Activation of rat liver cytosolic phosphatidic acid phosphatase by nucleoside diphosphates.

Phosphatidic acid phosphatase (EC 3.1.3.4) was purified 30-fold by ammonium sulfate fractionation and hydroxyapatite chromatography from the soluble fraction of rat liver. ADP was found to stimulate the enzyme activity with half-maximal stimulation at 0.2 mM. Similar effects were seen when ADP was replaced by GDP or CDP. In contrast, ATP inhibited the enzyme; half-maximal inhibition observed at 0.2 mM. Again, the degree of inhibition did not differ when GTP or CTP replaced ATP. Thus, the structure of the base part of the nucleotide was not critical for mediating these effects. The positions of the phosphate groups in the nucleotide structure were however found to be of importance for the enzyme activity. Variations in the structure of the phosphate ester bound at the 5'-position had a pronounced effect on phosphatidic acid phosphatase activity. The effect of nucleotides depended on pH, and the inhibition by ATP was more pronounced at pH levels lower than 7.0, whereas the stimulatory effect of ADP was virtually the same from pH 6.0 to pH 8.0. The enzyme showed substrate saturation kinetics with respect to phosphatidic acid, with an apparent Km of 0.7 mM. Km increased in the presence of ATP, whereas both apparent Vmax and Km increased in the presence of ADP, suggesting different mechanisms for the action of the two types of nucleotides. The results indicated that physiological levels of nucleotides with a diphosphate or a triphosphate ester bound at the 5'-position of the ribose moiety influenced the activity of phosphatidic acid phosphatase. The possibility is discussed that these effects might be of importance for the regulation of triacylglycerol biosynthesis.

Adenosine Diphosphate↗
PubMed1989

Effect of thiazide treatment on biliary lipid composition in healthy volunteers.

An increased incidence of cholecystitis has been observed in thiazide-treated patients. In order to test the possibility that the therapy might have caused an increase in the cholesterol saturation of gallbladder bile, biliary lipid composition was determined in fasting duodenal bile obtained from 10 healthy individuals after cholecystokinin injection, before and after 3 weeks of treatment with hydrochlorthiazide. The mean relative concentration of cholesterol was increased in 6 subjects, from 4.7 to 5.6 mol%, and the cholesterol saturation of bile was increased in 7, from 69 to 81%. These preliminary results indicate that thiazide treatment may to some extent increase biliary cholesterol saturation, and this may, at least in part, explain the higher prevalence of symptomatic gallbladder disease during such therapy.

Adult↗
PubMed1989

Bile acid synthesis in humans: regulation of hepatic microsomal cholesterol 7 alpha-hydroxylase activity.

The present work tested the hypothesis that portal venous bile acids regulate the activity of the cholesterol 7 alpha-hydroxylase and studied the influence of hepatic microsomal free cholesterol concentration on the enzyme activity. Operative liver biopsies and samples of portal venous blood were obtained from a total of 61 patients with gallstones who were undergoing cholecystectomy. Fifteen of the patients were treated with cholestyramine (16 g/day) for 2-3 wk before operation and 23 patients with chenodeoxycholic acid (15 mg/kg.day) or ursodeoxycholic acid (15 mg/kg.day) for 3-4 wk before operation. Highly accurate methods based on isotope dilution-mass spectrometry were used for assay of the cholesterol 7 alpha-hydroxylase activity, the concentration of free cholesterol in the microsomes, and the levels of individual bile acids in portal venous blood. Cholestyramine treatment increased the cholesterol 7 alpha-hydroxylase activity about sixfold, from 7.6 +/- 1.1 (mean +/- SEM) to 45.7 +/- 6.7 pmol/min.mg protein. Administration of chenodeoxycholic acid reduced the enzyme activity considerably to 1.0 +/- 0.3 pmol/min.mg protein, whereas ursodeoxycholic acid did not significantly affect the enzyme activity (7.9 +/- 2.2 pmol/min.mg protein). The concentration of microsomal free cholesterol remained essentially unchanged in spite of a 45-fold variation in enzyme activity. There was a negative correlation between the absolute as well as the relative concentration of chenodeoxycholic acid in portal blood and the activity of the cholesterol 7 alpha-hydroxylase, whereas there was no correlation between the total concentration of bile acids and the enzyme activity. It is concluded that the composition of individual bile acids may be more important than the total concentration of bile acids in the portal vein for the regulation of the cholesterol 7 alpha-hydroxylase activity in humans. It is further concluded that chenodeoxycholic acid is a considerably stronger suppressor of bile acid synthesis than ursodeoxycholic acid.

Adult↗
PubMed1989

Biliary excretion of iron and ferritin in idiopathic hemochromatosis.

The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.

Adult↗
PubMed1989

Effects of somatostatin on hepatic bile formation.

Somatostatin is a peptide that has anticholeretic properties in the dog. The purpose of the present work was to investigate if somatostatin is an anticholeretic agent in humans also. The effects of intravenous infusion of somatostatin on hepatic bile flow and biliary electrolytes and secretion of biliary lipids were studied in 7 patients with complete biliary drainage who had been operated on for choledocholithiasis. Somatostatin, 250 microgram/h, was found to decrease the hepatic bile secretion by approximately 30%. The peptide also reduced the outputs of bile acids, cholesterol, and phospholipids and the outputs of sodium, potassium, and chloride. The concentrations of the biliary lipids were not significantly changed. Somatostatin inhibited the erythritol clearance in the 2 patients studied by approximately 25%. The present study thus provides evidence that somatostatin inhibits bile formation in humans. It appears as if the reduction in bile production is mainly due to decreased canalicular bile flow. It is possible that this effect of somatostatin is attributable to inhibition of bile acid synthesis or of transport-secretion of bile acids, or both.

Adult↗
PubMed1989

Oestrogen-induced changes in lipoprotein metabolism: role in prevention of atherosclerosis in the cholesterol-fed rabbit.

Administration of moderate pharmacological doses of oestrogen to cholesterol-fed rabbits for 12 weeks resulted in a dramatically retarded development of arterial lesions as compared to non-oestrogen-treated, cholesterol-fed rabbits (7% vs. 47% aortal involvement). Oestrogen treatment was associated with a retarded increase in plasma cholesterol, and five times higher high density lipoprotein (HDL) to very low density lipoprotein (VLDL) cholesterol ratio. Expression of hepatic lipoprotein receptor activity, as detected by heparin-releasable binding of 125I-hypercholesterolaemic VLDL, was heavily suppressed by cholesterol feeding. Administration of oestrogen modulated this response and resulted in higher receptor expression. In accordance, oestrogen treatment resulted in a less prominent reduction of 125I-hypercholesterolaemic VLDL clearance in the cholesterol-fed rabbits. VLDL from both groups of cholesterol-fed animals stimulated cholesteryl ester synthesis in cultured macrophages to the same extent. Thus, in rabbits under a dietary cholesterol load, oestrogen counteracted hepatic lipoprotein receptor suppression, reduced plasma VLDL- and increased plasma HDL-cholesterol levels, and to a large extent abolished the development of atherosclerosis.

Animals↗
PubMed1989

Lipid lowering in severe familial hypercholesterolaemia: efficacy and safety of a new regenerating system for selective apheresis of apolipoprotein B-containing lipoproteins.

Preliminary experience of the efficacy and safety of a new regenerating system for selective extracorporeal removal of apolipoprotein B-containing lipoproteins is described. Four patients with familial hyperlipoproteinaemia were studied on 10 occasions. A system of two, parallel, dextran sulphate cellulose columns was used, and plasma was processed continuously by passage through one of the columns while the other was being regenerated. With this procedure, reductions of very low density and low density lipoprotein cholesterol levels by 73 and 43%, respectively, could be achieved after treatment for 2.5-3 h (1000-3200 ml of plasma volume). No clinically relevant changes in the concentrations of other plasma proteins, including high density lipoproteins, were observed, and the treatment was well tolerated. We conclude that continuous selective apolipoprotein B apheresis is a safe and efficient lipid-lowering procedure which may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.

Apolipoproteins B↗
PubMed1989

Unsatisfactory effect of cyclosporin A treatment in Crohn's disease: a report of five cases.

Five patients with chronic continuous Crohn's colitis were treated with peroral Cyclosporin A (CyA) for 3 months in an open, uncontrolled pilot trial. The CyA dose was 10 mg kg-1 d-1 the first month of study, and thereafter 5 mg kg-1 d-1. Three of the patients initially showed some response to the treatment with decreases in the Crohn's disease activity index, but subsequently deteriorated. In one patient the condition was unchanged and another clearly worsened. Increases in serum creatinine levels were noted in three patients, and all of these also had decreased 51Cr-EDTA clearance indicating impaired renal function. Hypertrichosis and hyperaesthesia were also noted as side-effects. This study does not support the use of CyA in the short-term treatment of Crohn's disease in the colon.

Adult↗
PubMed1989

Early determination of serum lipids and apolipoproteins in acute myocardial infarction: possibility for immediate intervention.

Early identification of elevated cholesterol in patients with acute myocardial infarction (MI) is of interest as secondary prevention can then be initiated when patients are highly motivated. However, since the lipid pattern changes during acute MI, screening for lipid disturbances is often not performed until 6 months later. We prospectively studied lipid and apolipoprotein levels during acute MI and 3 and 6 months later in 123 consecutive acute MI patients, mean age 64 +/- 10 (SD) years, who were admitted within 24 h from onset of symptoms, mean delay 5.5 h. Blood was taken at admission to the Coronary Care Unit (CCU), the first morning in the CCU, at hospital discharge and at 3 and 6 months follow-up. Patients were fasted overnight except at admission, and no specific dietary advice was given. Total serum cholesterol, triglycerides, and apolipoprotein (apo) A-I concentrations did not differ significantly (1-3%) between CCU admission and the 3 and 6 months control. During the subsequent hospital period, lipid concentrations generally decreased and at discharge were 15-25% below those at 6 months follow-up (P less than 0.001). The highest correlations between immediate CCU determination and 6 months follow-up were obtained for cholesterol (r = +0.71) and apo B (r = +0.67). Thus, lipid levels obtained early at CCU admission in acute MI patients are representative of the patient's baseline levels which are in contrast to those registered later during hospital stay. This information could be used to identify patients for early intervention.

Adult↗
PubMed1989

Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma.

To characterize the effects of estrogen treatment on the metabolism of LDL we studied six males with metastatic prostatic carcinoma before and during the initiation of therapy; a repeated study was performed in five participants after 3-6 mo of treatment. The fractional catabolic rate (FCR) of autologous 125I-LDL was calculated both from elimination curves of plasma radioactivity and from urine/plasma (U/P) radioactivity ratios. Within 1-2 d of onset of estrogen therapy a more rapid decay of plasma radioactivity occurred, and FCR measured from U/P ratios increased by 20%. Concomitantly, LDL cholesterol levels decreased by 16%. After 3-6 mo of treatment FCR determined by both techniques was almost doubled, and LDL cholesterol was reduced by 34%. This occurred despite a 29% increase in the calculated synthesis rate of LDL. Tissue culture studies demonstrated that the receptor affinity of LDL isolated from patients on long-term estrogen therapy was reduced. We conclude that a profound increase in LDL catabolism is induced through administration of pharmacological doses of estrogen in males, and hypothesize that this is the consequence of an increased expression of hepatic LDL receptors. This enhanced catabolism of LDL leaves LDL particles in plasma with lower affinity for the LDL receptor.

Aged↗
PubMed1989

Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma.

To assess if and by which mechanisms pharmacological estrogen treatment induces gallstone disease, we examined patients with recently diagnosed prostatic cancer randomly allocated to estrogen therapy (n = 37) or orchidectomy (n = 35). According to gallbladder ultrasonography, after 1 yr new gallstones had developed in 5 of 28 estrogen-treated patients, compared with 0 of 26 orchidectomized patients (P = 0.03). Estrogen therapy for 3 mo increased the relative concentration of cholesterol and cholesterol saturation of bile by approximately 30% (n = 10). Serum LDL cholesterol was reduced by approximately 40%, and its relative change related inversely to that of bile cholesterol (Rs = -0.77). There were no changes in biliary or serum lipids after orchidectomy (n = 9). Secretion rates of biliary lipids were measured with a duodenal perfusion technique. Patients on chronic estrogen therapy (n = 5) had approximately 40% higher biliary excretion rates of cholesterol than age-matched controls (n = 7). Phospholipid secretion was also higher, but no difference in bile acid secretion was found. We conclude that an increased hepatic secretion of cholesterol results in increased cholesterol saturation of bile and an enhanced rate of gallstone formation during estrogen treatment. The changes in bile cholesterol seem to be related to the induced changes in serum lipoprotein metabolism.

Aged↗
PubMed1989

Treatment of psoriasis vulgaris with a synthetic metalloporphyrin and UVA light.

Sn-protoporphyrin is a synthetic heme analogue which inhibits the catabolism of natural heme to bilirubin and can suppress a wide variety of experimentally induced or naturally occurring forms of jaundice in animals and man. Ten patients, 9 of whom were substantially or completely unresponsive to other forms of therapy, received 2.0 mumol/kg body weight of Sn-protoporphyrin on day 0 of this study followed by UVA light treatment for 21 days. Severity of psoriatic plaques, clinically scored (erythema 0-3; scaling, 0-3; infiltration, 0-3;) declined from a mean +/- score of 7 +/- 0.3 on day 0 to 3.6 +/- 0.7 on day 21. Psoriatic lesions were improved in all patients and in some the effect was dramatic. No deleterious side effects were registered. As shown in this study, one-day treatment with Sn-protoporphyrin followed by conventional UVA light treatment may be a useful therapeutic modality for psoriasis patients and merits further investigation.

Adult↗
PubMed1989

Studies on acyl-coenzyme A: cholesterol acyltransferase activity in human liver microsomes.

The aim of the present study was to characterize the acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity in human liver microsomes. Liver biopsies were obtained from patients undergoing elective cholecystectomy under highly standardized conditions. In 34 patients the enzyme activity of the microsomal fraction averaged 6.6 +/- 0.7 (mean +/- SEM) pmol.min-1.mg protein-1 in the absence of exogenous cholesterol. Freezing of the liver biopsy in liquid nitrogen increased the enzyme activity five- to sixfold. Similarly, freezing of the microsomal fraction prepared from unfrozen liver tissue increased the enzyme activity about twofold. These results may help to explain previous disparate results reported in the literature. The enhanced ACAT activity obtained by freezing was at least partly explained by a transfer of unesterified cholesterol to the microsomal fraction and possibly also by making the substrate(s) more available to the enzyme. Preincubation of the microsomal fraction, prepared from unfrozen liver tissue, with unlabeled cholesterol increased the enzyme activity about fivefold. This finding indicates that hepatic ACAT in humans can also utilize exogenous cholesterol as substrate. Addition of cholesterol to frozen microsomes prepared from unfrozen liver tissue increased the ACAT activity two- to threefold, whereas addition of cholesterol to microsomes prepared from frozen liver tissue did not further increase the enzyme activity. No evidence supporting the concept that ACAT is activated-inactivated by phosphorylation-dephosphorylation could be obtained by assaying the enzyme under conditions similar to those during which the human HMG-CoA reductase is inactivated-activated.

Acyl Coenzyme A↗
PubMed1989

Effects of treatment with clofibrate, bezafibrate, and ciprofibrate on the metabolism of cholesterol in rat liver microsomes.

The effects of treatment of rats with clofibrate, bezafibrate, and ciprofibrate on the hepatic metabolism of cholesterol were studied in rat liver microsomes. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity, regulating cholesterol biosynthesis, was unaffected by clofibrate and ciprofibrate and slightly decreased (20%) by bezafibrate. Also cholesterol 7 alpha-hydroxylase activity, governing bile acid biosynthesis, was unaffected by clofibrate and was reduced by 25-30% in the two other groups of rats. A major new finding was that all three fibric acid derivatives reduced ACAT (acyl-coenzyme A:cholesterol acyltransferase) activity, catalyzing the esterification of cholesterol, by 50-70%. The hepatic content of free and esterified cholesterol was determined in the bezafibrate-treated rats. The concentration of microsomal cholesteryl ester was about 60% lower in the treated rats compared to the controls whereas the concentration of total cholesterol was unchanged.

Animals↗
PubMed1988

Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in mouse peritoneal macrophages.

The lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl-(HMG-) CoA reductase in cultured mouse peritoneal macrophages has been investigated. In contrast to what has been reported for other cells, HMG-CoA reductase activity is not suppressed by normal serum or by normal low density lipoproteins (LDL) from humans or dogs. Suppression of reductase activity occurred when cells were cultured in the presence of beta-migrating very low density lipoproteins (beta-VLDL) or LDL from hypercholesterolaemic dogs, or LDL modified by acetoacetylation. Human beta-VLDL from an atypical type III hyperlipoproteinaemic patient was also effective, as was apolipoprotein (apo) E-containing high density lipoproteins (HDL) from cholesterol-fed dogs (apo-E HDLc). The results indicate that cholesterol biosynthesis in mouse peritoneal macrophages is regulated by lipoprotein cholesterol entering via receptor-mediated endocytosis. Normal LDL were not effective because of the poor binding and uptake of these lipoproteins by the apo-B, E (LDL) receptor. Only beta-VLDL, apo-E HDLc, and hypercholesterolaemic LDL were avidly taken up by this receptor and were able to suppress HMG-CoA reductase. Acetoacetylated LDL were internalized via the acetyl-LDL (scavenger) receptor. Thus, mouse macrophages differ from human fibroblasts and smooth muscle cells in their physiological regulation of cholesterogenesis.

Animals↗