Gene expression of LDL receptor, HMG-CoA reductase, and cholesterol-7 alpha-hydroxylase in chronic renal failure

BACKGROUND: Chronic renal failure (CRF) is associated with an atherogenic lipid profile and an increased risk of ischaemic cardiovascular disease. The associated hyperlipidaemia is reportedly ameliorated by erythropoietin (Epo) therapy. According to a recent report, rats studied 3 weeks after 5/6 nephrectomy and fed a high- protein diet exhibited increased activities of hepatic HMG-CoA reductase (HMG-CoAR) and cholesterol 7 alpha-hydroxylase (Ch-7 alpha- H), despite normal corresponding mRNA values. DESIGN AND METHODS: This study was designed to examine the effects of naturally progressing CRF of longer duration as well as those of Epo therapy on gene expressions of the key factors involved in hepatic cholesterol metabolism, i.e., LDL receptor (LDLR), HMG-CoAR, and Ch-7 alpha-H. Sprague-Dawley rats were randomized to the CRF group (5/6 nephrectomy), Epo-treated CRF group (given Epo 150 U/kg/twice weekly) and sham-operated, placebo- treated normal controls. They were allowed free access to regular rat chow and studied 6 weeks after surgery. Liver mRNAs and protein mass or activities of the above factors were studied. RESULTS: Plasma cholesterol concentration was significantly increased in the CRF group (P < 0.001) and was modestly lowered (P < 0.05) by Epo therapy. However, microsomal cholesterol concentration and LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA as well as HMG-CoAR activity, and Ch-7 alpha-H and LDLR protein mass measurements were virtually identical in the three groups. Thus, hepatic LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA and protein measurements in rats with CRF were similar to those of the normal control group representing an inappropriate response to the associated hypercholesterolemia. Epo therapy led to partial amelioration of CRF- associated hypercholesterolaemia with no discernible effect on hepatic tissue expression of the above factors.      

Role of adrenergic innervation in regulation of secretory activity of cells of the rat supraoptic nucleus

To study the role of the noradrenergic innervation in the production of peptide neurohormones by cells of the supraoptic nucleus (SON) the substance 6-hydroxydopamine (6-HDA), which causes selective destruction of noradrenergic terminals, was used. The intensity of fluorescence of these terminals in the region of SON 7 days after intraventricular injection of 6-HDA in a dose of 250 g was sharply reduced and morphological pictures reflecting activation of hormone production by SON cells were observed. According to the results the noradrenergic innervation evidently inhibits synthesis of peptide neurohormones by SON cells and regulates the transport and secretion of peptide neurohormones from the posterior lobe of the pituitary into the general circulation.Laboratory of Neuroendocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 518–520, November, 1979.     

Randomized trial of two administration schedule of bonephos (Clodronate) in patients with painful bone metastasis

A randomized study of two intravenous schedules of Clodronate showed that a single 4-hour infusion of 1500 mg Clodronate proved significantly more effective than the traditional 2 hours infusion of 300 mg during 5 days. The regimen may prove preferable in therapy of patients with painful bone metastases.