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B Angelin

Publications and source records attributed to B Angelin.

At least 109 records · Page 6Linked to original sources
PubMed1993

Adipocyte beta-adrenoceptor sensitivity influences plasma lipid levels.

Catecholamine stimulation of lipolysis through adipocyte beta-adrenoceptors is of major importance for the regulation of lipid mobilization from adipose tissue. The influence of adipocyte beta-receptor sensitivity as assessed by an isoprenaline bioassay on circulating lipid levels was investigated in 46 healthy and drug-free subjects. beta-Receptor sensitivity was inversely related to total plasma triglycerides (r = -.62), very low density lipoprotein cholesterol (VLDL-C) (r = -.56), VLDL triglycerides (r = -.52), and apolipoprotein B (r = -.41). These relationships remained significant after adjustment for age, sex, body mass index, waist/hip ratio, fat cell volume, and circulating levels of insulin, noradrenaline, and adrenaline. beta-Receptor sensitivity accounted for 40% of the variance in total plasma triglycerides. beta-Receptor subtype sensitivity and binding capacity were also determined in fat cells using terbutaline (beta 2) and dobutamine (beta 1) bioassays and radioligand binding. Multiple regression analysis revealed that terbutaline sensitivity correlated inversely with total plasma triglycerides, apolipoprotein B, VLDL-C, and VLDL triglycerides (partial r from -.56 to -.42), but there was no correlation between dobutamine sensitivity and blood lipids (partial r from .05 to .18) or between receptor binding and blood lipids (partial r from .01 to .28). Thus, the lipolytic beta-receptor sensitivity in fat cells appears to play a hitherto-unrecognized role for lipoprotein metabolism, in particular that of VLDL. This relationship is receptor-subtype specific, particularly involving beta 2-receptors, and seems to be localized to a postreceptor step in lipolysis regulation. Low sensitivity may be of importance for the development of hypertriglyceridemia.

Adipose Tissue↗
PubMed1993

Stimulation of rat hepatic low density lipoprotein receptors by glucagon. Evidence of a novel regulatory mechanism in vivo.

We studied the influence of glucagon on hepatic LDL receptors and plasma lipoproteins in rats. A dose-dependent (maximum, threefold) increase in LDL-receptor binding was evident already at a dose of 2 x 4 micrograms, and detectable 3 h after injection; concomitantly, cholesterol and apolipoprotein (apo) B and apoE within LDL and large HDL decreased in plasma. LDL receptor mRNA levels were however unaltered or reduced. Hepatic microsomal cholesterol was increased and the enzymatic activities of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase in hepatic microsomes were reduced. Insulin alone increased receptor binding and receptor mRNA levels twofold, but plasma cholesterol was unchanged and plasma apoE and apoB increased. Administration of insulin to glucagon-treated animals reduced the LDL-receptor binding to control levels and apoB appeared in LDL particles. Estrogen treatment increased LDL-receptor binding and mRNA levels five- and eightfold, respectively. Combined treatment with glucagon and estrogen reduced the stimulation of LDL-receptor mRNA levels by 80% although LDL-receptor binding was unchanged. Immunoblot analysis showed that glucagon increased the number of hepatic LDL receptors. We conclude that glucagon induces the number of hepatic LDL receptors by a mechanism not related to increased mRNA levels, suggesting the presence of a posttranscriptional regulatory mechanism present in the liver in vivo.

Animals↗
PubMed1993

Photodynamic properties of Sn-protoporphyrin: clinical investigations and phototesting in human subjects.

Pure synthetic metalloporphyrins have been developed for experimental and clinical use as inhibitors of heme oxygenase, the rate limiting enzyme in the catabolism of heme to bilirubin. Tin (Sn)-protoporphyrin is one such compound, which potently suppresses bilirubin production and thus jaundice in animals and man. We have previously reported that this metalloporphyrin in conjunction with UVA might be useful as a treatment for psoriasis. To assess the photodynamic properties of Sn-protoporphyrin, 31 subjects were investigated with regard to photosensitivity. In all subjects, phototesting using UVB, UVA, and visible light as well as photopatch testing was performed. Our investigations revealed that 16 of the 31 individuals treated with Sn-protoporphyrin developed a mild photosensitivity, mainly erythema of the hands and face, and in some cases a mild conjunctivitis. The duration of this sensitivity, which in no case caused discomfort, was dose-dependent and ranged from several weeks to 1-3 months. After administration of Sn-protoporphyrin, lower thresholds were found for both UVA and visible light, but the sensitivity for UVB was normal and photopatch tests were negative. In summary, the photosensitivity observed during Sn-protoporphyrin administration was of limited duration and magnitude and did not occur in all subjects. Thus, the combination of photoactive synthetic metalloporphyrins and artificial light might prove to be useful as a regimen for the treatment of skin disease.

Adult↗
PubMed1993

Apolipoprotein E polymorphism in a healthy Swedish population: variation of allele frequency with age and relation to serum lipid concentrations.

We analyzed blood samples from 407 healthy Swedish individuals, 244 men and 163 women, ages 17 to 86 years, for apolipoprotein (apo) E isoforms and serum triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol. Parallel genotyping by means of polymerase chain reaction (PCR)-amplified DNA was performed in 200 subjects. Identical results were obtained by genotyping and phenotyping in 95% of all subjects analyzed. The apo E allelic frequencies were 7.8% for epsilon 2, 71.9% for epsilon 3, and 20.3% for epsilon 4. Compared with other Caucasian populations, the present population had a high relative allelic frequency of epsilon 4. The epsilon 4 frequency decreased with increasing age and was significantly lower in individuals > 60 years of age (14.7%). When controlling for age and sex, there were strong correlations between total serum and LDL cholesterol and the various epsilon alleles. The epsilon 4 and epsilon 3 alleles correlated positively with serum cholesterol and the epsilon 4 allele correlated positively with LDL cholesterol. In contrast, HDL cholesterol and serum triglycerides did not show any correlation to the allele types. Thus, the results demonstrate a considerable age variation of the epsilon allele frequency among healthy Swedes and an influence of apo E alleles on serum and LDL cholesterol concentrations.

Adolescent↗
PubMed1992

Importance of growth hormone for the induction of hepatic low density lipoprotein receptors.

This investigation was undertaken to determine the possible role of growth hormone (GH) in the hormonal regulation of hepatic low density lipoprotein (LDL) receptor expression. Treatment of normal rats with estrogen (ethynylestradiol, 5 mg/kg per day) increased the number of hepatic LDL receptors, and the LDL receptor mRNA levels were increased 2.4-fold. However, when hypophysectomized rats were treated with estrogen, the hepatic LDL receptor number and the mRNA levels only increased slightly. Treatment with GH was important to restore the induction of hepatic LDL receptors in hypophysectomized estrogen-treated rats. Further, the hypocholesterolemic effect of estrogen was abolished in hypophysectomized rats, and GH reversed this effect. To assess the effect of GH in humans, hepatic LDL receptor binding activity was determined in liver biopsy specimens from gallstone patients pretreated with GH (12 international units/day) prior to operation. GH administration induced hepatic LDL receptors approximately 2-fold, and this was accompanied by a 25% decrease in serum cholesterol. The LDL receptor stimulation caused by GH treatment was of similar magnitude as that observed upon 3 weeks of treatment with an established hypolipidemic drug (pravastatin or simvastatin). The data show that GH has an important role in the regulation of hepatic LDL receptors and suggest that GH secretion may be important for the control of plasma LDL levels in humans.

Adult↗
PubMed1992

Metoprolol does not reduce platelet aggregability during sympatho-adrenal stimulation.

The possibility that beta-adrenoceptor blockers, especially beta 1-selective agents might inhibit platelet function is of considerable interest, as this might be of pathophysiological importance in cardiovascular diseases. Platelet function, however, is difficult to assess and in vivo related data are scarce. The effect of one week of treatment with metoprolol 200 mg/day on platelet aggregability during mental stress (colour word conflict test; CWT) and low and high dose adrenaline infusions has been evaluated in a double-blind, placebo-controlled, cross-over study in 10 healthy male volunteers. Platelet function in vivo was assessed using ex vivo filtragometry, and the urinary excretions of beta-thromboglobulin (HMW beta-TG) and 11-dehydro-TxB2 (a thromboxane metabolite). Conventional in vitro aggregometry and the urinary levels of 2,3-dinor-6-keto-PGF1 alpha (a prostacyclin metabolite) were also studied. During the interventions there was increased platelet aggregability in vivo, as filtragometry readings were shortened by 41 +/- 11% during high dose adrenaline infusion, urinary HMW beta-TG levels increased and urinary 11-dehydro-TxB2 tended to increase. In contrast, platelet sensitivity to ADP in vitro was reduced. The urinary 2,3-dinor-6-keto-PGF1 alpha levels were increased during the interventions. Despite the cardiovascular and biochemical signs of beta-adrenoceptor blockade at rest and during the interventions, metoprolol failed to influence platelet function in vivo, as measured by ex vivo filtragometry, or urinary HMW beta-TG or 11-dehydro-TxB2 levels. It tended rather to enhance the stress response measured by ex vivo filtragometry. Platelet aggregability in vitro and urinary 2,3-dinor-6-keto-PGF1 alpha levels were not altered by metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance.

The possibility of an inhibitory effect of spironolactone on the biliary clearance of digoxin has been investigated in 6 healthy subjects. Plasma clearance and the renal and biliary clearance of digoxin were determined twice at steady state (digoxin 0.5 to 1 mg.d-1 p.o. for 6 days), alone or in combination with spironolactone 200 mg daily, after an intravenous dose of digoxin (0.7 x oral dose) on Day 7. Plasma and urine were collected for 48 h. Biliary clearance of digoxin was determined on Day 8 by a duodenal perfusion technique. During spironolactone treatment plasma digoxin clearance tended to be lower (255 vs 224 ml/min; P = 0.057) and renal clearance significantly lower (166 vs 144 ml/min), while the biliary clearance of digoxin remained unchanged (106 vs 103 ml/min). Thus, spironolactone reduced the renal clearance of digoxin by an average of 13%, without affecting its biliary clearance.

Adult↗
PubMed1992

Dose-dependent absorption of amoxicillin in patients with an ileostomy.

Amoxicillin was given as single doses of 375, 700, 1500, 3000 and 6000 mg an oral suspension to four volunteers with an ileostomy and with no active intestinal disease after an overnight fast. The excretion of amoxicillin and its penicilloic acid was followed in samples taken from the ileostomy and in urine produced over 6 h. Beta-lactamase activity was measured in ileal fluid and none was found. The percentage of the dose recovered from the ileostomy increased successively from 8% at the lowest dose to 77% at the highest dose. A complementary excretion pattern of amoxicillin was found in the urine, amounting to 70% recovery at the lowest dose to 23% at the highest dose. The results confirm the dose-dependence of the absorption of amoxicillin, which could at least in part be due to specialised absorption of this drug in humans.

Adult↗
PubMed1992

Hepatic cholesterol metabolism in estrogen-treated men.

Operative liver biopsies were obtained from two male patients who developed gallstone disease during estrogen treatment of metastatic prostatic carcinoma. The heparin-sensitive binding of 125I-low-density lipoprotein (LDL) to liver homogenates (reflecting the expression of the LDL receptor) was determined, together with the activities of the rate-limiting enzymes in cholesterol synthesis [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase], bile acid production (cholesterol 7 alpha-hydroxylase), and cholesterol esterification (acyl CoA:cholesterol acyl transferase). The results were related to data available in 18 patients (5 male, 13 female) who underwent cholecystectomy because of gallstone disease. The hepatic 125I-LDL-binding activity was increased threefold compared with five controls, and the activity of HMG-CoA reductase was increased twofold. There was no major difference in the activities of cholesterol 7 alpha-hydroxylase or acyl CoA:cholesterol acyl transferase. The concentration of free and total cholesterol in liver microsomes was approximately 30% lower in the estrogen-treated men than in 11 controls. The results indicate that estrogen at pharmacological doses stimulates hepatic LDL-receptor expression and HMG-CoA reductase activity in men. The increased LDL-receptor expression could in part explain the enhanced plasma clearance of injected 125I-LDL and hence the reduction in plasma LDL cholesterol previously shown to occur in estrogen-treated men.

Aged↗
PubMed1992

Somatostatin does not block the effect of vasoactive intestinal peptide on bile secretion in man.

The effects of intravenously administered somatostatin and vasoactive intestinal peptide (VIP) on bile secretion were studied in 10 patients with complete biliary fistulas. The two peptides were administered both separately and simultaneously. During the infusion of vasoactive intestinal peptide, bile secretion increased by 85%, whereas during somatostatin infusion it decreased by 40%. When the peptides were administered together, the VIP-induced choleretic effect was not reduced by somatostatin. Vasoactive intestinal peptide infusion increased bicarbonate concentration and output, whereas somatostatin had the opposite effect. The output of chloride also increased following vasoactive intestinal peptide infusion but decreased following somatostatin infusion. The concentration of chloride was unaffected by somatostatin whereas it was decreased by vasoactive intestinal peptide. The output of bile acids was unaffected by vasoactive intestinal peptide and decreased by somatostatin infusion, whereas total lipid concentration increased during somatostatin infusion and decreased when vasoactive intestinal peptide was added. It is concluded that, in man, somatostatin acts on the bile acid-dependent canalicular bile secretion and also, to some extent, on the ductular secretion, whereas vasoactive intestinal peptide acts strictly at the ductular level. The effects of the two peptides on bile secretion are independent of each other.

Adult↗
PubMed1992

Metabolism of plasma low density lipoproteins in familial combined hyperlipidaemia: effect of acipimox therapy.

Ten male patients with familial combined hyperlipidaemia (FCHL) were studied with regard to LDL metabolism and composition. The FCHL patients had higher LDL levels than healthy controls (5.4 +/- 1.4 vs. 3.7 +/- 0.7 mmol l-1; P < 0.005) and a higher rate of production of the lipoprotein (15.8 +/- 3.1 mg kg-1 d-1 in FCHL vs. 13.1 +/- 1.8 mg kg-1 d-1 in the normals; P < 0.005). The fractional catabolic rate of LDL was low-normal in the FCHL patients, with a high level of interindividual variation. The actual individual LDL cholesterol level within the FCHL patient group appeared to be more closely associated with the LDL apoB FCR value than the rate of production of the particle. Analysis of the LDL particles from FCHL patients revealed a relative enrichment in triglycerides, while the cholesterol content of the lipoprotein was normal. Institution of acipimox therapy in 8 patients reversed the high rate of synthesis of LDL (15.2 +/- 3.5 mg kg-1 d-1) to a more normal level (13.9 +/- 4.0 mg kg-1 d-1; P = 0.08), while the FCR did not change significantly. In conclusion, patients with FCHL show an apparent overproduction of LDL apoB, while the actual degree of LDL elevation appears to be dependent on the clearance capacity of the lipoprotein, measured as LDL apoB FCR. The overproduction defect of LDL apoB can, at least in part, be managed by treatment with the nicotinic acid analogue acipimox.

Adult↗
PubMed1992

Hormonal regulation of serum Lp (a) levels. Opposite effects after estrogen treatment and orchidectomy in males with prostatic carcinoma.

Serum concentrations of lipoprotein (a) [Lp (a)] were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with estrogen (n = 15) or orchidectomy (n = 16). Estrogen was given as oral ethinylestradiol, 150 micrograms daily, combined with intramuscular polyestradiol phosphate, 80 mg/mo. The baseline levels were similar in both groups, but 6 mo after initiation of therapy, serum Lp (a) levels were decreased approximately 50% in the estrogen-treated group (P less than 0.001) in contrast to a 20% increase (P less than 0.01) in the orchidectomized group. Concomitantly, LDL cholesterol decreased by 30% and HDL cholesterol increased by almost 60% in the estrogen-treated patients. There was no relationship between the change in LDL cholesterol and Lp (a) reduction. In conclusion, Lp (a) levels in males were found to drastically decrease upon estrogen treatment and to increase after orchidectomy, suggesting that sex hormones, and particularly estrogens, exert a regulatory role on the serum Lp (a) level in man.

Aged↗
PubMed1992

Effects of growth hormone on low-density lipoprotein metabolism.

GH appears to play an important role in mediating the increase in hepatic LDL receptor expression that occurs in response to pharmacological oestrogen treatment. Furthermore, in normal individuals there is evidence of an increased number of hepatic LDL receptors in response to GH, resulting in an accelerated elimination rate of the LDL particle and a subsequent lowering of LDL cholesterol. Further studies on lipoprotein metabolism in patients with GH deficiency, and also in patients with hypercholesterolaemia, would therefore be of interest.

Biological Transport, Active↗