No abstract

A B S T R A C T The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from -6 to +75 mg/dl; mean change, +29 mg!dl; P <0.001). Increases reduction of LDL receptor activity (-74%; P < 0.01), quantified as the rate of degradation of 125I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism.The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = -0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade 125I-LDL after derepression by preincubation for 72 h in lipoproteindeficient medium (r = -0.74, P < 0.001). Thus, differences between individuals in the responses of the plasma lipoproteins to dietary cholesterol appear to be related in part to differences in the capacity of peripheral cells to catabolize LDL and to downregulate cholesterol synthesis.

Lipid peroxides are thought to be formed by free radicals and may play an important role in the development of atheromatous vascular disease. We have investigated the relationship between lipids, lipoproteins, coagulation factors, and lipid peroxides (measured as thiobarbituric acid reacting species (TBARS) in Type 2 diabetic patients with macrovascular disease. Eighteen diabetic and 20 non-diabetic subjects with clinical evidence of ischaemic heart disease and/or peripheral vascular disease were investigated, together with 28 healthy subjects without evidence of vascular disease. TBARS concentrations in non-diabetic (mean 5.0 (95% Cl 4.5-5.7) mumol l-1) and diabetic groups (5.6 (5.1-6.0) mumol l-1) with macrovascular disease were not significantly different although values were higher in both groups of patients with vascular disease by comparison with control subjects (2.7 (2.4-3.1) mumol l-1, p less than 0.001). Significant univariate correlations between TBARS concentrations and measures of blood glucose control (fructosamine, blood glucose and HbA1) were found for all 66 subjects (r = 0.35-0.42, p less than 0.01-p less than 0.001), although no independent association between these parameters and TBARS was demonstrated in multiple regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Background The incidence of syncope exhibits a daily pattern with more occurrences in the morning, possibly due to influences from the endogenous circadian system and/or the daily pattern of behavioral/emotional stimuli. This study tested the hypothesis that the circadian system modulates cardiovascular responses to postural stress, leading to increased susceptibility to syncope at specific times of day. Methods and Results Twelve subjects underwent a 13-day in-laboratory protocol, in which subjects’ sleep-wake cycles were adjusted to 20 hours for 12 cycles. A 15-minute title-table test (60° head-up) was performed ~4.5 hours after scheduled awakening in each cycle so that twelve tests in each subject were distributed evenly across the circadian cycle. Out of 144 tests, signs/symptoms of presyncope were observed in 21 tests in 6 subjects. These presyncope events displayed a clear circadian rhythm (P=0.028) with 17 cases (81%) in the circadian phase range corresponding to ~22:30-10:30 (4.25 times of the probability from the other half of the circadian cycle). Significant circadian rhythms were also observed in hemodynamic and autonomic function markers (blood pressure, heart rate, epinephrine, norepinephrine, and indices of cardiac vagal tone) that may underlie the circadian rhythm of presyncope susceptibility. Conclusion The circadian system affects cardiovascular responses to postural stressors resulting in greater susceptibility to presyncope during the biological night. This finding suggests that night-shift workers and people with disrupted sleep at night may have great risk of syncope due to their exposure to postural stressors during the biological night.