The respiratory burst activity of peripheral leukocytes from 17 patients with chronic renal failure and 12 healthy individuals was assessed using the technique of whole-blood chemiluminescence (CL). Luminol- and lucigenin-dependent CL was measured in two dilutions of venous blood following stimulation with serum-treated zymosan or phorbol myristate acetate, and the CL peaks associated with a polymorphonuclear leukocyte count of 10⁴ /ml were calculated. The mean CL peaks for the patients were significantly higher than those for the controls in all experimental designs (p < 0.05). This enhanced leukocyte respiratory burst activity was not associated with the underlying renal abnormality or with the type of dialysis treatment, but may have been related to the induction of tissue enzymes which is known to occur in uremia.

dicates that young children (< 2 years) have a different bladder shape than older children and need to be assessed by a specific formula to improve the accuracy of ultrasonographic estimation of their bladder volume. The influence of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, on quantitative and qualitative changes in lipoprotein metabolism was investigated in 18 patients (group I, 10 with primary kidney disease and group II, 8 with diabetic nephropathy) with nephrotic syndrome. Nephrotic patients exhibited severe hyperlipidemia (serum cholesterol 390+_ 17 mg/dl an triglyceride 335-+42 mg/dl; mean -+ SEM) and had significantly higher lipoprotein (a) [Lp(a)] levels (54_+12 mg/dl; median 31 mg/dl, p <0.01) compared with 20 healthy subjects (mean 12_+ 1.8 mg/dl; median 7 mg/dl). Fifty-six percent of the patients and 15% of the controls had values greater than 30 mg/dl. Treatment with simvastatin in increasing doses over a period of three months (13 patients received 40 mg/day and 5 patients 20 mg/day at the end of the third month) reduced LDL-cholesterol in both groups of patients (35% and 54%) as well as apolipoprotein B (apoB) (31% and 46%) significantly, but Lp (a) levels were not influenced (57_+21 vs 59___20 and 50_+14 vs 53 _+ 16 mg/dl, respectively). On the other hand a complex change in lipoprotein composition occurred. The ratio of LDL apoB/LDL cholesterol-ester increased significantly (0.75_+0.03 to 0.84+_0.03 and 0.80 __ 0.03 to 1.02 ___ 0.1, respectively) and cholesterol concentration in VLDL (64 _+ 16 to 39 _+ 7 and 74 _+ 18 to 55 _+ 74 mg/dl, respectively) was reduced. Therefore, the ratio of triglycerides/cholesterol in VLDL increased (2.89_+0.32 vs 4.10_+0.50 and 3.56_+0.30 to 5.86_+0.97, respectively), indicating VLDL formation poor in cholesterol and rich in triglycerides. The data show that simvastatin profoundly influences the composition of triglyceride and cholesterol rich lipoproteins in patients with nephrotic syndrome. Although these alterations in lipoprotein composition appear to be favorable, the strikingly elevated levels of the atherogenic lipoprotein(a) were not influenced.

Lovastatin and bezafibrate have proved effective in lowering low-density-lipo-protein (LDL) cholesterol and elevating high-density-lipoprotein (HDL) cholesterol. We compared their tolerability, safety, and effects on lipoproteins and urinary mevalonate excretion in a short-term study. Forty patients with primary hypercholesterolemia were enrolled in a single-blind randomized study with a diet/placebo period of 8 weeks and a treatment period of 12 weeks. Twenty patients received lovastatin (final average dose 70.5 mg/day), and 20 patients received bezafibrate 400 mg/day. LDL cholesterol was lowered by 35% (from 323 to 208 mg/dl) with lovastatin and by 8% (from 289 to 264 mg/dl) with bezafibrate. HDL cholesterol increased by 21 and 20% with lovastatin and bezafibrate, respectively. Twenty-four-hour urinary mevalonic acid output decreased by 37% during treatment with lovastatin and by 2% during treatment with bezafibrate. Thus, the lowering of cholesterol by lovastatin, but not by bezafibrate, can be attributed to inhibition of HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase. Both lovastatin and bezafibrate are well tolerated.

The effects of calmodulin antagonists on the amount of LDL receptor (LDL-R) mRNA in cultured human fibroblasts was examined by hybridization with a fragment of LDL-R cDNA. In a 'Northern' blot the fragment hybridized to a 5.3-kilobase RNA, as expected for LDL-R mRNA. The concentration of this RNA was increased in preparations from cells that were treated with trifluoperazine or W-7 [N-(6-aminohexyl)-5-chloronaphthalene-1-sulphonamide). The selectivity of the increase was established by using a probe for /3-actin mRNA. In dot-blot hybridization it was observed that the calmodulin antagonists cause 2-4-fold relative increase in the amount of LDL-R mRNA. INTRODUCTIONThe low-density-lipoprotein (LDL) receptor, a transmembrane cell-surface glycoprotein, mediates endocytosis of macromolecular lipoprotein ligands. The regulation of the activity of the LDL receptor has been studied extensively in both cultured cells and experimental animals. Although the primary structure (Yamamoto et al., 1984) and synthesis of the LDL receptor (Goldstein et al., 1985) and the organization of the gene encoding this glycoprotein (Suidhof et al., 1987) have been elucidated, little is known about the mechanisms of the regulation of the synthesis of the LDL receptor. In human skin fibroblasts, depletion of cholesterol enhances, and loading with cholesterol lowers, the activity of the LDL receptor . The activity of the LDL receptor Chao et al., 1979) and the amount of its mRNA (Ma et al., 1986a,b) are enhanced in livers of rats, hamsters and rabbits treated with mevinolin (Ma et al., 1986b) or with pharmacological doses of

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