Beta-adrenergic effects on cellular cholesterologenesis and low density lipoprotein metabolism.
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Biomedical subjects
Publications and source records attributed to L O'Donnell.
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The effects of catecholamines on the regulation of lipoprotein metabolism have not been defined. We examined the effects of subcutaneously administered slow-release preparations of norepinephrine (2 mg/kg) and isoproterenol (0.2 mg/kg) on the serum lipoproteins of New Zealand White rabbits. Drugs or control suspension were administered daily to three groups of normally fed and three groups of cholesterol-fed rabbits, and lipoprotein analysis was performed at intervals over a 60-hour period. In the normally fed animals, norepinephrine increased the serum levels of triglyceride and phospholipid by factors of 2.4 (P less than .01) and 1.35 (P less than .05), respectively, compared with control animals at 60 hours, but had no effect on serum cholesterol. All components of serum very low density lipoproteins (VLDL: triglyceride, cholesterol, phospholipid, and protein) were significantly (P less than .01) elevated by norepinephrine in the normally fed animals. In the cholesterol-fed animals, norepinephrine at 60 hours significantly increased total serum cholesterol, triglyceride, and phospholipid concentrations by factors of 1.7 (P less than .05), 5.0 (P less than .01), and 1.6 (P less than .05), respectively, compared with controls. The norepinephrine effects in these animals was due to significant elevation of total VLDL and low density lipoproteins (LDL) and all their elemental components. Isoproterenol produced no significant effect on serum lipoprotein levels in the normally fed rabbit, but in cholesterol-fed animals it produced a rise in total serum VLDL and LDL triglyceride concentrations compared with controls at 60 hours. These data demonstrate that catecholamines are involved in the regulation of lipoprotein metabolism.
In a survey of 237 hospital workers involved in the care of AIDS patients at a major AIDS inpatient-care facility, negative attitudes toward AIDS and AIDS patients (AIDS-phobia) and AIDS-related job stress (AIDS-stress) were common. In multivariate analyses, AIDS-phobia is significantly higher among older staff, those having low contact with AIDS patients (AIDS-contact), and those holding homophobic attitudes. AIDS-phobic attitudes and low AIDS-contact can be interpreted as predicting each other. Finally, AIDS-stress is predicted by low contact with AIDS and AIDS-phobic attitudes.
Changes in plasma catecholamines, lipoproteins and dietary intake were examined in 13 medical students during a 3-month period prior to their examinations, and in 12 controls. In the medical students mean +/- s.e.(mean) plasma cholesterol increased over the study period (3.98 +/- 0.16 v. 4.26 +/- 0.16 mmol/l, P less than 0.05) and this was reflected by a rise in low-density lipoprotein cholesterol (2.53 +/- 0.15 v. 2.71 +/- 0.17 mmol/l, P less than 0.05). Both supine adrenaline (0.45 +/- 0.05 v. 0.70 +/- 0.07 nmol/l, P less than 0.01) and noradrenaline (2.74 +/- 0.18 v. 3.40 +/- 0.31 nmol/l, P less than 0.05) increased over this period. Apart from a decline in the modest alcohol consumption (9.1 +/- 3.45 v. 2.6 +/- 1.4 g/day, P less than 0.02) there was no change in dietary intake in the medical students. There were no significant changes in plasma catecholamines, lipoproteins or dietary intake in control subjects over the study period. Changes in catecholamines and lipoproteins occurring in association with chronic psychological stress may contribute to the increased coronary heart disease mortality associated with Type A behaviour and stressful life events.
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Adrenergic control of liver cholesterol metabolism was studied in the rabbit. The effects of noradrenaline (alpha 1, alpha 2, beta 2 agonist) and isoprenaline (beta 1, beta 2 agonist) on 3-hydroxy-3-methylglutaryl coenzyme A reductase, acyl-coenzyme A: cholesterol-o-acyltransferase (cholesterol acyltransferase) and cholesterol 7 alpha-hydroxylase, the rate-limiting enzymes of cholesterol biosynthesis and esterification and bile acid synthesis, respectively, were examined in the normally fed and cholesterol-fed male New Zealand White rabbit. Isoprenaline increased the activities of hydroxymethylglutaryl CoA reductase and cholesterol acyltransferase approx. 12-fold and 5-fold, respectively, in normally fed rabbits. Noradrenaline, by contrast, produced an effect only on hydroxymethylglutaryl CoA reductase, the activity of which was increased 3-fold in these animals. Neither catecholamine had an effect on hydroxymethylglutaryl CoA reductase in the cholesterol-fed rabbit. Isoprenaline decreased the activity of cholesterol acyltransferase by approx. 40% and increased the activity of cholesterol 7 alpha-hydroxylase 2-fold in the cholesterol-fed rabbit compared to cholesterol-fed controls. Noradrenaline had no effect on either cholesterol acyltransferase or cholesterol 7 alpha-hydroxylase in either the normally fed or the cholesterol-fed rabbit. We suggest that beta 2-adrenergic stimulation by isoprenaline in the normally fed rabbit may enhance cholesterol synthesis and storage, but that in the cholesterol-fed rabbit, it facilitates the elimination of cholesterol from the body by increasing the rate of bile acid synthesis.
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A 35 year old man was treated for stage IIA Hodgkin's disease by radiation to the upper thorax, axillae and neck. Three years later he presented with intractable and ultimately fatal congestive heart failure. Autopsy revealed massive biventricular hypertrophy with widespread subendocardial fibrosis and myocardial infarction, but with little coronary artery disease. Such a complex of features has not previously been described after radiation therapy and cannot be adequately explained by other known causes of heart muscle disease. Ventricular hypertrophy with extensive subendocardial fibrosis may be part of the spectrum of radiation heart disease.
Cardiac papillary fibroelastomas are rare and benign primary tumors in the cardiac valves or occasionally the mural endocardium. Before 1977, these tumors were diagnosed exclusively at postmortem examination. Over the last few years, a handful of cases have been diagnosed in vivo by echocardiography. In this report, we describe the first tricuspid valve papillary fibroelastoma detected by echocardiography in an adult. Clinical and echocardiographic features are discussed.
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Pronounced differences in pharmacokinetic parameters of antipyrine have been found in the 20-day pregnant hooded Wistar rat when compared with nonpregnant controls. Total body clearance falls significantly from 5.93 to 3.5 ml/min/kg in the pregnant rat whereas no significant increase in antipyrine volume of distribution occurs. These changes result in an increase in antipyrine half-life from 109 to 223 min in the pregnant rat. This study demonstrates that reduced hepatic mono-oxygenase capacity exists in the pregnant rat and that this can markedly affect drug clearance in there animals.