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Biomedical subjects

B Angelin

Publications and source records attributed to B Angelin.

At least 73 records · Page 4Linked to original sources
PubMed1996

Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males.

When given orally, estrogens, as well as androgens, lower serum lipoprotein (a)[Lp(a)]levels. To determine whether these effects occur also after parenteral administration of steroids, Lp(a) levels were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with parenteral estrogen (n = 8) or orchidectomy (n = 6). One group of healthy male volunteers (n = 9) was studied after parenteral administration of testosterone. Estrogen was given as im polyestradiol phosphate, 240 mg twice monthly, and testosterone was given as im injections, 250 mg/week. In the orchidectomized subjects, Lp(a) levels increased by 20% by month 3 after treatment (P < 0.05). In spite of drastic changes in serum hormone levels, no change in Lp(a) levels was observed in the estrogen-treated subjects. Concomitantly, low-density lipoprotein cholesterol levels were lowered by 15% and high-density lipoprotein cholesterol levels increased by 20%. Testosterone administration lowered Lp(a) levels by 20% (P < 0.05). No significant changes in serum lipid levels were observed in the testosterone-treated subjects or in the orchidectomy group. Thus, during parenteral administration of estrogens or androgens, diverging effects on Lp(a) and serum lipoproteins were observed. In particular, the mode of administration of estrogen influenced the response in Lp(a) levels. This suggests that the regulatory role of sex hormones on serum Lp(a) levels may depend on their capability to influence hepatic metabolic pathways of Lp(a).

Adult↗
PubMed1996

Increased prevalence of atherosclerotic wall changes in patients with hyperlipidaemia after renal transplantation.

OBJECTIVES: The initial aim of this study was to evaluate the possibility of influencing atherosclerosis in hyperlipidaemic renal transplant patients by lowering blood lipids with gemfibrozil treatment. DESIGN: Although this double-blind, randomized trial was stopped after 6 months owing to the suspicion of drug interference, we report here on the results of baseline ultrasonographic examinations. SETTING: The outpatient clinic at the Department of Transplantation Surgery, Huddinge University Hospital, Huddinge, Sweden. SUBJECTS AND METHODS: The carotid arteries were examined in 16 out of the 19 kidney transplant patients included in the study using an ultrasonographic duplex scanner. MAIN OUTCOME MEASURES: Plaque occurrence and the common carotid intima-media thickness of the renal transplant recipients were compared to the same parameters in a normotensive control group of approximately the same age from a previous study. RESULTS: An increased prevalence of plaque (75% of the patients having plaque on one or both sides) was seen in the hyperlipidaemic renal transplant patients in comparison with the control group (16%; P < 0.001). The common carotid intima-media complex was thicker (P < 0.05), and the lumen diameter and the calculated cross-sectional intima-media area were greater (P < 0.01-0.001) in the transplant recipients. CONCLUSIONS: Markedly increased atherosclerotic wall changes are seen in the carotid arteries of patients with hyperlipidaemia after renal transplantation.

Adult↗
PubMed1996

Expression of very low density lipoprotein receptor in the vascular wall. Analysis of human tissues by in situ hybridization and immunohistochemistry.

The recently cloned very low density lipoprotein (VLDL) receptor binds triglyceride-rich, apolipoprotein-E-containing lipoproteins with high affinity. The observation that VLDL receptor mRNA is abundantly expressed in extracts of tissues such as skeletal muscle and heart, but not liver, has led to the hypothesis that this receptor may facilitate the peripheral uptake of triglyceride-rich lipoproteins. However, little information is available concerning the types of cells that express this receptor in vivo. As expression of the VLDL receptor in the vascular wall might have important implications for the uptake and transport of triglyceride-rich lipoproteins, and perhaps facilitate the development of atherosclerosis in hypertriglyceridemic individuals, we used in situ hybridization and immunohistochemistry to determine whether VLDL receptor mRNA and protein was expressed in human vascular tissue. We observed expression of the receptor by both endothelial and smooth muscle cells within normal arteries and veins, as well as within atherosclerotic plaques. In the latter, the VLDL receptor was also expressed by macrophage-derived foam cells. The widespread distribution of the VLDL receptor in vascular tissue suggests a potentially important role for this receptor in normal and pathophysiological vascular processes.

Arteriosclerosis↗
PubMed1996

VLDL receptor mediates the uptake of human chylomicron remnants in vitro.

The VLDL receptor has been described as a new member of the LDL receptor supergene family that specifically binds VLDL in vitro via apolipoprotein E and lipoprotein lipase. Both apolipoprotein E and lipoprotein lipase are constituents of chylomicron remnants, another triglyceride-rich lipoprotein which has been proposed as a physiological ligand for the VLDL receptor. We used human chylomicron remnants to study their uptake into LDL, receptor-deficient Chinese hamster ovary cells overexpressing the human VLDL receptor. The uptake into these cells was compared to that into cells transfected with an empty transfection vector. Human chylomicron remnants were produced in vitro by hydrolysis with lipoprotein lipase, and were labeled with 125I. The uptake of these remnants into the cells overexpressing the VLDL receptor was found to be about 3-fold higher than the uptake into the control cells. The addition of a surplus of either apolipoprotein E or inactivated lipoprotein lipase to the remnants led to an increase in particle uptake. The chylomicron remnant uptake was inhibited by addition of the 39 kDa receptor associated protein These in vitro experiments strongly support the idea that the VLDL receptor is a physiological receptor for chylomicron remnants. The increase of receptor-mediated uptake induced by the addition of apoE or lipoprotein lipase underlines the role of these two proteins in this process.

Animals↗
PubMed1996

Gemfibrozil reduces thrombin generation in patients with combined hyperlipidaemia, without influencing plasma fibrinogen, fibrin gel structure or coagulation factor VII.

A double-blind, placebo-controlled, cross-over study was conducted in 21 men with combined hyperlipoproteinaemia to examine if lipid-lowering treatment with gemfibrozil (10-12 weeks) affects blood coagulation and fibrin gel structure at rest or during mental stress. Gemfibrozil lowered plasma triglycerides by 57 +/- 4%, whereas high density lipoprotein (HDL) cholesterol increased by 22 +/- 5%. Gemfibrozil lowered the triglyceride content of low density lipoprotein (LDL). Gemfibrozil reduced the plasma concentrations of thrombin-antithrombin complex (TAT) and prothrombin fragment F1 + 2 (F1 + 2), both at rest and during mental stress. However, there were no effects of gemfibrozil treatment on the plasma concentrations of fibrinogen, factor VII antigen, activated factor VII (VIIa) or activated factor XII (XIIa), or on fibrin gel structure. Acute mental stress per se did not influence coagulation factors, reaction products or fibrin gel structure, or their responses to the study drug. Thus, gemfibrozil reduced thrombin generation in men with combined hyperlipoproteinaemia, without influencing the plasma levels of fibrinogen, VIIa and XIIa, or fibrin gel structure. Attenuation of thrombin generation may contribute to the primary-preventive effects of gemfibrozil on coronary heart disease.

Adult↗
PubMed1996

Metabolism and excretion of ropivacaine in humans.

The pharmacokinetics, biotransformation, and urinary excretion of ropivacaine (Naropin), a new local anesthetic agent, have been studied in six healthy male volunteers after a 15-min iv infusion of 152 mumol (50 mg) of [14C]ropivacaine, with a specific radioactivity of 22.5 kBq/mumol (8.8 kBq/mg). Blood, urine, and feces were collected for up to 96 hr after administration. The plasma and urine samples were analyzed for unchanged ropivacaine and for four of its metabolites, i.e. 3-OH-2',6'-pipecoloxylidide (3-OH-PPX), 4-OH-ropivacaine, 3-OH-ropivacaine, and the N-dealkylated metabolite PPX, using GC and HPLC methods. The presence of 2,6-xylidine in plasma was also analyzed. The metabolites were quantified after acidic hydrolysis. The radioactivity could be followed in plasma for up to 14 hr after administration, with ropivacaine being the predominant compound in the early samples. The concentrations of the aforementioned metabolites in plasma were below or just above the lower limit of quantification, and no 2,6-xylidine was detected. The maximum plasma concentration of ropivacaine was 5.9 +/- 2.6 microM (1.6 +/- 0.7 mg/liter), with an elimination half-life of 2.0 +/- 0.3 hr and a total plasma clearance of 397 +/- 127 ml/min. The maximum plasma concentration value for the total radioactivity was 5.5 +/- 2.4 microM (1.5 +/- 0.7 mg/liter) and the elimination half-life was 5.4 +/- 2.9 hr. [14C]Ropivacaine and its metabolites were mainly excreted in the urine, with a total recovery of 86 +/- 3% in the urine and 9 +/- 1% in the feces after 96 hr. Most of the radioactivity (about 68%) was excreted within 12 hr. Ropivacaine was extensively metabolized, and only 1 +/- 0.6% of the dose was excreted unchanged in the urine. The major metabolite identified in the urine was conjugated 3-OH-ropivacaine, which was excreted to an extent of 37 +/- 3% of the dose. The urinary excretion of 4-OH-ropivacaine was < 1%, whereas the N-dealkylated metabolites PPX and 3-OH-PPX accounted for 2 and 3% of the dose, respectively. An additional hydroxylated metabolite, 2-OH-methyl-ropivacaine, was tentatively identified in the urine of some volunteers, accounting for about 4-15% of the dose.

Adult↗
PubMed1995

Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: reduced activity of cholesterol 7 alpha-hydroxylase.

Bezafibrate is a hypolipidemic fibric acid derivative known to induce cholesterol supersaturation of bile. To characterize its effects on hepatic cholesterol metabolism, 31 normolipidemic, normal-weight patients with gallstones undergoing cholecystectomy were studied. Eleven patients (5 men) were randomized to treatment with bezafibrate, 200 mg three times daily for 4 weeks before operation; the remaining 20 patients (5 men) served as nontreatment controls. At operation, a liver biopsy specimen was obtained under standardized conditions and several important parameters of cholesterol metabolism were assayed. Bezafibrate treatment lowered total plasma cholesterol and triglycerides 30% and 37%, respectively. The hepatic cholesterol 7 alpha-hydroxylase activity was reduced by approximately 60% in the bezafibrate treated patients compared with the controls, whereas the acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was similar in the two groups. The total 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity was increased twofold in the treated patients, whereas the active enzyme remained about the same as in the controls. The low-density lipoprotein (LDL) receptor binding activity was unaffected by the treatment. Bezafibrate treatment significantly reduces cholesterol 7 alpha-hydroxylase activity, and it is suggested that this may play an important role for the development of supersaturated bile during such therapy.

Adult↗
PubMed1995

Studies on lipoprotein metabolism in a family with jejunal chylomicron retention.

We describe two siblings with fat malabsorption and jejunal chylomicron retention. Plasma lipoproteins were studied in the patients and their first-degree relatives. The patients were a 14-year-old girl and her 8-year-old brother. Compared to healthy controls, they both had low fasting plasma concentrations of plasma total, HDL, and LDL cholesterol, as well as of apolipoproteins A-I and B. No increase in plasma lipoprotein levels or detectable apo B-48 was observed following an oral fat load. Histological studies of jejunal biopsy specimens obtained during fasting and 1 h postprandially showed severe steatosis, and an apparent block of chylomicron secretion from the endoplasmic reticulum into the Golgi apparatus was observed by electron microscopy. Liver biopsy specimens showed moderate steatosis and ultrastructural changes similar to those in the enterocytes. One healthy sister had a normal plasma lipoprotein pattern, and showed increased plasma triglyceride levels as well as the presence of apo B-48 following an oral fat load. Both parents had normal plasma total cholesterol levels, but clearly reduced fasting concentrations of HDL cholesterol and apo A-I. At least in this family, determination of plasma apo A-I levels might thus prove useful in the identification of heterozygotes.

Adolescent↗
PubMed1995

Gemfibrozil enhances platelet activity in patients with combined hyperlipoproteinemia.

A placebo-controlled crossover study was conducted to evaluate whether lipid-lowering with gemfibrozil (10 to 12 weeks) affects platelet function in vivo at rest and during mental stress in 21 men with combined hyperlipoproteinemia. Gemfibrozil lowered plasma triglycerides and total and VLDL cholesterol (P < .001 for all), whereas HDL cholesterol increased (P < .001). Gemfibrozil increased platelet counts by 18% (P < .001) and, according to filtragometry measurements, enhanced overall (means of rest and stress values) platelet aggregability in vivo (P = .014); this effect was more evident during mental stress (P = .027) than at rest (P = .18). Moreover, the urinary excretion of 11-dehydro-thromboxane-B2 was 54% higher during treatment with gemfibrozil (P < .001), whereas the excretion of beta-thromboglobulin in urine was unaltered. Plasma beta-thromboglobulin tended to be slightly elevated during active treatment (P = .15). Mental stress increased heart rate and catecholamine levels and elevated all cholesterol fractions (P < .01) and plasma beta-thromboglobulin (during placebo, P = .02), but platelet aggregability did not increase significantly. A positive correlation was found between 11-dehydrothromboxane-B2 excretion and LDL cholesterol levels during placebo (r = .62, P = .0057). In conclusion, gemfibrozil has beneficial effects on plasma lipoprotein levels but enhances several aspects of platelet activity in vivo and increases platelet counts. These changes might be prothrombotic and thus adverse for the hyperlipidemic patient. Primary preventive effects of gemfibrozil might be enhanced if a platelet inhibitor such as aspirin is administered with gemfibrozil.

Adult↗
PubMed1995

Hormonal regulation of serum lipoprotein(a) levels. Contrasting effects of growth hormone and insulin-like growth factor-I.

In response to treatment with growth hormone, serum levels of lipoprotein(a) increase, while those of LDL cholesterol decrease. To establish if increased levels of insulin-like growth factor-I may be of importance for these changes, we analyzed serum lipoprotein concentrations in 11 male patients with idiopathic osteoporosis who were treated with growth hormone (2 IU.m-2.d-1) or insulin-like growth factor-I (80 micrograms.kg-1.d-1) in a randomized, double-blind, cross-over study. LDL cholesterol was reduced by 0.7 mmol/L (P < .01) during growth hormone treatment but was not affected when the same patients received insulin-like growth factor-I. In contrast, mean lipoprotein(a) levels increased from 519 to 571 mg/L (P < .03) in response to growth hormone but were reduced from 538 to 478 mg/L (P < .04) during treatment with insulin-like growth factor-I. These results indicate that growth hormone exerts its effects on lipoprotein metabolism independent of insulin-like growth factor-I. Furthermore, the results suggest that treatment with insulin-like growth factor-I may reduce lipoprotein(a) levels.

Adult↗
PubMed1995

Impaired activation of adipocyte lipolysis in familial combined hyperlipidemia.

The pathophysiology of familial combined hyperlipidemia (FCHL) is unknown, but altered lipid turnover in peripheral tissues as well as hepatic overproduction of apolipoprotein B have been suggested as possible causes. In the present study, we explored whether a change in triglyceride breakdown by lipolysis in fat cells is present in FCHL. Lipolysis activation by catecholamines was examined in isolated subcutaneous adipocytes from 10 patients with FCHL and 22 healthy control subjects. Lipolysis rate was linear for at least 3 h in both groups. However, a marked (approximately 65%) decrease in the lipolytic response to noradrenaline was found in FCHL. This was also true when lipolysis was maximally stimulated at the receptor level with isoprenaline (nonselective beta-adrenergic agonist), at the adenylyl cyclase level with forskolin, or at the level of the protein kinase hormone-sensitive lipase complex with dibutyryl cAMP. The maximum enzymatic activity of hormone-sensitive lipase was decreased by approximately 40% in FCHL. On the other hand, the lipolytic sensitivity of alpha 2-, beta 1-, and beta 2-adrenoceptors was normal in this condition, as was the number and affinity of beta 1- and beta 2-adrenoceptors. Variations in the maximum lipolysis rate correlated significantly with the variations in hormone-sensitive lipase activity in the whole material, and with the serum values for triglycerides, HDL cholesterol and apoB lipoprotein within the control group, but the serum triglyceride values in FCHL were higher than this correlation predicted. In conclusion, the data demonstrate a marked resistance to the lipolytic effect of catecholamines in fat cells from patients with FCHL, in spite of normal adrenoceptor function. The lipolytic defect appears predominantly to be due to a defect in hormone-sensitive lipase, and may be of importance in the pathophysiology of FCHL.

Adipocytes↗
PubMed1995

Growth hormone specifically stimulates the expression of low density lipoprotein receptors in human hepatoma cells.

Human GH (hGH) has been shown to stimulate hepatic low density lipoprotein (LDL) receptor expression in man in vivo. To further characterize this effect in vitro, we determined the expression of LDL receptors in cultured human hepatoma (HepG2) cells exposed to hGH. After incubation with hGH, stimulation of LDL receptors appeared at a concentration of 0.25 nM hGH. The presence of hGH receptors on HepG2 cells could be demonstrated by immunocytochemistry using a hGH receptor-specific monoclonal antibody. Binding studies, using 125I-labeled hGH, revealed high affinity binding with the appropriate somatogenic specificity. The LDL receptor induction was specific for hGH, as both bovine GH and recombinant human PRL were without effect. The LDL receptor stimulation occurred in parallel with increased levels of LDL receptor messenger RNA. Inclusion of dexamethasone and thyroid hormone in the incubation medium enhanced the LDL receptor stimulation by hGH. Although incubation with insulin-like growth factor-I (IGF-I) stimulated LDL receptor expression, the hGH-induced stimulation was unaltered after preincubation of cells with a monoclonal mouse anti-IGF-I antibody, suggesting that the release of IGF-I is not involved in LDL receptor stimulation by hGH. We conclude that hGH specifically induces the LDL receptor in cultured HepG2 cells at both the protein and the messenger RNA level, and that the induction is independent of IGF-I release.

Carcinoma, Hepatocellular↗
PubMed1995

Growth hormone treatment does not alter biliary lipid metabolism in healthy adult men.

GH is important for the hepatic low density lipoprotein (LDL) receptor induction that occurs after estrogen treatment. GH treatment increases liver LDL receptors and lowers plasma LDL cholesterol in man. Estrogen treatment enhances biliary secretion of cholesterol, resulting in supersaturation of bile and an increased risk of gallstone formation. The present study was undertaken to investigate whether GH treatment also influences biliary lipid metabolism in humans. Twelve healthy male volunteers (mean age, 31 +/- 1 yr) were studied before and during the third week of treatment with recombinant human GH (0.1 IU/kg.day). Plasma lipids, bile acid kinetics, and biliary lipid composition were monitored. Plasma total and LDL cholesterol levels were reduced by 10% in response to therapy. However, no significant changes were observed in the biliary lipid composition or cholesterol saturation of gallbladder bile. Furthermore, there were no changes in chenodeoxycholic acid or cholic acid kinetics. The reduction of plasma LDL cholesterol in response to GH treatment in healthy adult men is not associated with detectable changes in biliary lipid metabolism. Thus, in contrast to estrogen, GH therapy of adults probably does not result in an increased risk of cholesterol gallstone development.

Adult↗
PubMed1994

Lack of association between apolipoprotein E allele epsilon 4 and sporadic Alzheimer's disease.

Apolipoprotein E (apoE) is a protein involved in the transport of lipids and a component of Alzheimer's disease (AD) plaques. There are three common alleles of the apoE gene, designated epsilon 2, epsilon 3 and epsilon 4. An association between familial and sporadic AD and the epsilon 4 allele was recently reported. We have investigated Swedish Alzheimer patients and controls. The epsilon 4 allele frequency in familial and sporadic cases and in controls was 47, 22 and 18%, respectively. There was no significant difference between sporadic AD and controls but in familial cases the increased epsilon 4 allele frequency previously reported was confirmed.

Aged↗