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This study examines the effects of increased dietary cholesterol (6 eggs/d) on the metabolism of low density lipoproteins in a group of seven healthy volunteers. Egg supplementation raised high density and low density lipoprotein cholesterol levels by 18 and 40%, respectively. The composition of the low density lipoprotein was unaltered and therefore the number of circulating particles must have increased. Kinetic studies indicated that this was due primarily to a 23% rise in the rate of synthesis of the lipoprotein. Catabolism was also affected. The fractional removal rate of native low density lipoprotein fell by 10% (P less than 0.05). However, the clearance of the 1,2 cyclohexanedione-treated lipoprotein remained unchanged (control fractional clearance rate [FCR] = 0.188 pools/d; cholesterol feeding FCR = 0.183 pools/d). Therefore, the reduction in low density lipoprotein catabolism appeared to be due to a fall in receptor activity. Consequently, an increased sterol load (34.2 mumol/kg per d vs. 27.7 mumol/kg per d in the control phase, P less than 0.02) was channelled into the receptor-independent route during egg feeding.

Plasma lipoproteins were estimated in ten hypertensive subjects (mean age 51 +/- 11.2 yr), before, 6 wk and 6 mth following treatment with Sotalol 320 mg/day. Heart rate fell sequentially throughout the study (p less than 0.01) and although there was a sequential fall in mean blood pressure this did not reach statistical significance. There was a significant increase in plasma triglyceride concentration from a basal value of 1.87 +/- 1.064 to 2.50 +/- 0.877 mmol/l (p less than 0.005) at 6 mth. No significant change was found in very low density, low density and high density lipoprotein cholesterol or apolipoprotein concentrations (Apo A-I, Apo A-II, Apo B). We conclude that Sotalol exerts a similar influence on plasma lipoproteins as other non-cardioselective beta-adrenoceptor blockers without intrinsic sympathomimetic activity and its use does not constitute an increased risk of developing atherosclerosis, when compared with other beta-blockers.

This study examines the potential influence of genetic variation on the metabolism of LDL. Restriction fragment length polymorphisms (RFLP) of the gene coding for apo B were identified using the endonucleases Xba I, Eco RI, and Msp I in a group of 19 subjects with moderate hyperlipidemia. There was a significant association between the Xba I polymorphism and the total fractional clearance rate (FCR) of LDL. The individuals with the X1X1 genotype had, on average, a 22% higher FCR (P less than 0.025) than those with the genotype X2X2 (X2 allele = presence of Xba I cutting site). This difference was attributable to increased clearance by the receptor-mediated pathway of LDL catabolism. In this group of subjects, there was no association of LDL kinetic parameters and RFLPs of the LDL receptor gene or the AI- CIII- AIV gene cluster. The data suggest that variation in apo B itself, presumably acting through variable binding to the LDL receptor, makes a significant contribution to the rate of catabolism of LDL.

This study examines the kinetic basis for the increment in plasma low density lipoprotein (LDL) levels that accompanies the fenofibrate treatment of severely hypertriglyceridemic (HTG) patients. Seven HTG men with a mean plasma triglyceride level of 1470 mg/dl were treated for 6 weeks. During treatment, their plasma triglyceride level fell by 77% and their cholesterol level by 41%. The fall in very low density lipoprotein (VLDL) cholesterol level was reciprocated by increments in the cholesterol level in both LDL and high density lipoproteins (HDL); the rise in HDL was confined to HDL3. LDL catabolism was examined before and during therapy using native and chemically modified tracers in an attempt to distinguish receptor-mediated from non-receptor-mediated clearance. In their basal state, the hypertriglyceridemic subjects overcatabolized both the native and the modified lipoprotein, implying that the non-receptor pathways were hyperactive. The mean fractional clearance rate of LDL via the receptor pathway was not significantly different from normal. Fenofibrate therapy corrected the patients' hypercatabolism, reducing the receptor-independent fractional clearance of apo LDL by 50% (from 0.48 to 0.24 pools/day; p less than 0.05). The mean fractional catabolic activity of the receptor route did not change, but when the increment in the plasma apo LDL concentration was taken into account, it was clear that the drug treatment was associated with an increase in the net amount cleared by the receptor pathway and with a reduction of lipoprotein uptake into receptor-independent routes.

Subfractions of CLDL (VLDL), Sf 100-400; CLDL2, Sf 60--100; VLDL3, Sf 20--60) and LDL (LDL), Sf 12--20; LDL2, Sf 6--12; LDL3, Sf 3--6) were isolated from the plasma of three normal, three type III and four type IV hyperlipoproteinemic subjects. In the type IV group, all VLDL subspecies were of normal composition but were increased in concentration in the order VLDL1 greater than VLDL2 greater than VLDL3. In the same subjects, although LDL2 was lowered and LDL3 increased, the total plasma LDL concentration was normal. All VLDL subfractions were elevated in the type III group, but in this case VLDL3 predominated. These subfractions were enriched in cholesteryl esters and depleted in triglyceride. In the LDL density range there was a shift of mass towards the least dense fraction, LDL1, which was of normal composition. EPR studies of the VLDL and LDL subfractions in a type IV subject demonstrated a decrease in fluidity with increasing density. The major change occurred between VLDL3 and LDL1 and was attributed to a substantial alteration in the cholesteryl ester : triglyceride ratio in the particle. A similar argument was used to explain thction in normal or type IV subjects. Particle diameters, determined by laser light-scattering spectroscopy were in good agreement with the values obtained by electron microscopy. This study provides a baseline for the examination of the relationship between the physical and metabolic properties of VLDL and LDL subfractions in type III and IV hyperlipoproteinemia.

1. The permeability of Paramecium to NH(4)OH is greater when the cells are exposed to light than it is when they are in darkness. 2. This change can be demonstrated in cells exposed to monochromatic red light, though it is small. It becomes greater as the wave lengths shorten, and is greatest in the near ultra-violet. 3. The permeability increases as the duration of exposure to light is prolonged. 4. These experiments demonstrate the necessity of controlling the illumination when using Paramecium in physiological tests.