Steroid-induced lipemia. A complication of high-dosage corticosteroid therapy

Bagdade, John D.

doi:10.1001/archinte.125.1.129

Cited by 42 publications

(11 citation statements)

References 11 publications

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“…(1) (2) where K D is the equilibrium dissociation constant for DEX for glucocorticoid receptor binding and K NS is the non-specific binding constant. The receptor density values were normalized by the protein content in the cytosol preparation [18].…”

Section: Methodsmentioning

confidence: 99%

“…Chronic, low doses of these drugs are used in the treatment of chronic diseases such as lupus erythematosus and rheumatoid arthritis [1]. Despite their beneficial effects, long-term therapy causes severe metabolic disorders similar to those observed with abnormalities in endogenous hormones [2][3][4][5] leading to Cushing's syndrome, hypertension, hyperglycemia, muscle atrophy, and dyslipidemia.…”

Section: Introductionmentioning

confidence: 99%

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Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Hazra

Pyszczynski

DuBois

et al. 2007

J Pharmacokinet Pharmacodyn

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Receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase (TAT) were evaluated in normal rats. A group of normal male Wistar rats were injected with 50 mg/kg methylprednisolone (MPL) intramuscularly at the nadir of their plasma corticosterone (CST) rhythm (early light cycle) and sacrificed at various time points up to 96 h post-treatment. Blood and livers were collected to measure plasma MPL, CST, hepatic glucocorticoid receptor (GR) mRNA, cytosolic GR density, TAT mRNA, and TAT activity. The pharmacokinetics of MPL showed bi-exponential disposition with two first-order absorption components from the injection NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript site and bioavailability was 21%. Plasma CST was reduced after MPL dosing, but resumed its daily circadian pattern within 36 h. Cytosolic receptor density was significantly suppressed (90%) and returned to baseline by 72 h resuming its biphasic pattern. Hepatic GR mRNA follows a circadian pattern which was disrupted by MPL and did not return during the study. MPL caused significant down-regulation (50%) in GR mRNA which was followed by a delayed rebound phase (60-70 h). Hepatic TAT mRNA and activity showed up-regulation as a consequence of MPL, and returned to their circadian baseline within 72 and 24 h of treatment. A mechanistic receptor/genemediated pharmacokinetic/pharmacodynamic model was able to satisfactorily describe the complex interplay of exogenous and endogenous corticosteroid effects on hepatic GR mRNA, cytosolic free GR, TAT mRNA, and TAT activity in normal rats.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Hazra

Pyszczynski

DuBois

et al. 2007

J Pharmacokinet Pharmacodyn

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“…Other conditions reported to have low PHLA include diabetes mellitus (69), hormonal steroid treatment (43,46,70), liver disease (65), alcoholism (71), renal failure (72), and pancreatitis (73). Specific changes also might be detected with hypolipidemic diets or drugs found to increase total PHLA (44,45,74 …”

Section: Selective Measurement Of Two Lipase Activities In Postheparimentioning

confidence: 99%

Selective Measurement of Two Lipase Activities in Postheparin Plasma from Normal Subjects and Patients with Hyperlipoproteinemia

Krauss¹,

Levy²,

Fredrickson³

1974

J. Clin. Invest.

425

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A B S T R A C T An assay has been developed for specific measurement of two different lipase activities in postheparin plasma. Lipoprotein lipase, derived from extrahepatic sources, is measured as protamine-inactivated lipase activity; hepatic lipase activity is protamine-resistant under the conditions of this assay. In 100 normal subjects, both enzyme activities were noted to be related to age and sex. Protamine-resistant lipase, which comprised 46-95% of the total activity, was highest in men over 18. Protamine-inactivated lipase activity was greatest in younger males and was agecorrelated in women, doubling between the second and sixth decades.In 12 patients with hyperchylomicronemia, including five previously shown to have familial type I hyperlipoproteinemia, protamine-inactivated lipase activity was markedly reduced, whereas protamine-resistant lipase was below normal in only 1. The results were not due to lack of plasma activator, presence of plasma inhibitor, or diet, and the deficiency was not overcome by increasing the provoking dose of heparin from 10 U to 75 U/kg. Mean values for both lipase activities were not reduced in 32 other patients with hyperchylomicronemia, nine with "floating beta" lipoproteins (type III hyperlipoproteinemia), and 23 with hyperprebetalipoproteinemia (type IV). Mean protamine-resistant lipase activity was below normal in a group of four women with hypothyroidism, in whom protamine-inactivated lipase was not reduced. Both of the lipase activities were capable of hydrolyzing lipid in very low-density lipoproteins, but the relative rate of hydrolysis of chylomicrons by protamine-resistant lipase was markedly limited. These results indicate the importance of distinguishing between lipases of hepatic and extra-

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“…In recent years it has been described in patients with endstage renal failure, and is apparently more pronounced in those undergoing haemodialysis treatment [2,3,9,13,20], A satisfactory explanation for this imbalance in lipid metabolism associated with renal disease is not yet known. A reduction in triglyceride metabolism by inhibition of lipoprotein lipase [24], stimulation of hepatic triglyceride synthesis in nephrotic syndrome [15], increased produc tion of very low density lipoproteins as a consequence of elevated basal plasma insulin concentrations in renal in sufficiency [3,33] and a hyperiipaemic effect of steroid therapy in patients after renal transplantation are thought to be possible causes [4,37], Hypercholesterolaemia and hypertriglyceridaemia ap pear to be important risk factors in the development of atherosclerosis and coronary heart disease [10.12,36,41, 42], This has also been observed in renal diseases with hyperlipaemia, patients with nephrotic syndrome [1] and patients after renal transplantation [25] are reported to manifest an accelerated development of atherosclerotic heart disease. A similar phenomenon in patients with ad vanced renal failure undergoing regular haemodialysis [5,31,32] has been unconfirmed by Burke et al [11], Recently in this journal an increased 'coronary risk' has also been reported in patients with analgesic nephropathy [26,30].…”

Section: Introductionmentioning

confidence: 99%

Hypercholesterolaemia and Hypertriglyceridaemia in Patients with Analgesic Nephropathy

Helber¹,

Wambach²,

Böttcher³

et al. 1980

Nephron

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Patients with analgesic nephropathy are reported to have a higher risk of atherosclerosis. One possible reason for this is a high incidence of hyperlipaemia in patients with analgesic nephropathy. In a retrospective study, serum cholesterol and serum triglyceride concentrations of patients with analgesic nephropathy and moderately restricted renal function were significantly higher compared to a control group with other renal diseases of similar age and degree of renal insufficiency. Hyperlipaemia in analgesic nephropathy is not explained by end-stage renal failure on one side or protein loss as in nephrotic syndrome on the other side. Some possible mechanisms for hyperlipaemia in analgesic nephropathy are discussed.

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Steroid-induced lipemia. A complication of high-dosage corticosteroid therapy

Cited by 42 publications

References 11 publications

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids

Selective Measurement of Two Lipase Activities in Postheparin Plasma from Normal Subjects and Patients with Hyperlipoproteinemia

Hypercholesterolaemia and Hypertriglyceridaemia in Patients with Analgesic Nephropathy

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