Letter: Reduction of serum-alkaline-phosphatase by clofibrate.
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Alkaline Phosphatase↗
Biomedical subjects
P N Demacker
Publications and source records attributed to P N Demacker.
Long-term treatment of type III hyperlipoproteinemia with clofibrate.
In this retrospective study we report the results of treatment with clofibrate during at least 7 years in 9 patients with severe type III hyperlipoproteinemia. Initial treatment consisted of a diet, restricted in fat and calories, because of insufficient response additional therapy with 2 g clofibrate daily was given. Serum cholesterol decreased significantly from 14.3 +/- 4.4 mmol/l (mean +/- SD), on diet therapy, to average annual values ranging from 9.0 +/- 4.9 to 7.9 +/- 2.0 and serum triglycerides decreased significantly from 5.6 +/- 1.9 to average annual values from 3.8 +/- 1.8 to 2.0 +/- 0.7, despite a slight gain in bodyweight. Serious side-effects did not occur. After several years of treatment with clofibrate the drug was withdrawn temporarily. Serum lipids increased significantly in all patients to a level, not different from that before the start of drug therapy. It is concluded that clofibrate is a strong hypolipidemic drug for the treatment of type III hyperlipoproteinemia, which does not lose efficacy even after 7 years of use.
Adult↗
Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects.
Oxidative modification of low density lipoprotein (LDL) has been implicated as a factor in the generation of macrophage-derived foam cells, the hallmark of atherosclerotic plaques. Because LDL consists of discrete subfractions with different physicochemical characteristics, the question arises as to whether these LDL subfractions differ in their susceptibility to oxidative modification. To answer this question, three LDL subfractions, LDL1, LDL2, and LDL3, were isolated from the plasmas of 11 healthy volunteers by density gradient ultracentrifugation. The LDL subfractions were oxidatively modified by incubation with copper ions. Differences in the subfractions' susceptibilities to lipid peroxidation were studied by measuring the formation of the 234-nm-absorbing oxidation products every 3 minutes on an ultraviolet spectrophotometer. A significant inverse linear relation was found between LDL subfractions and lag time (regression coefficient = -8.50, p less than 0.001), indicating that both the dense LDL3 and the light LDL2 were less well protected against oxidative modification than the very light LDL1. The LDL subfractions showed a positive linear relation with the rate of oxidation (regression coefficient = 0.46, p less than 0.001) and the amount of conjugated dienes formed in the LDL subfractions after 4 hours of oxidation (regression coefficient = 9.24, p less than 0.001). Thus, both LDL3 and LDL2 were more extensively modified in time than LDL1, which may be explained by the significantly higher concentration of polyunsaturated fatty acids in LDL3 (micromoles per gram LDL cholesterol) compared with LDL1 (Tukey's test, p less than 0.05). These results indicate that the more dense LDL subfractions, that is, LDL2 and LDL3, are more susceptible to oxidative modification and therefore may contribute more to foam cell formation than the less dense LDL subfraction LDL1.
Adult↗
Cholesterol-raising factor from boiled coffee does not pass a paper filter.
Previous studies have indicated that consumption of boiled coffee raises total and low density lipoprotein (LDL) cholesterol, whereas drip-filtered coffee does not. We have tested the effect on serum lipids of consumed coffee that was first boiled and then filtered through commercial paper coffee filters. Sixty-four healthy volunteers consumed six cups per day of this boiled and filtered coffee for 17 days. Then, they were randomly divided into three groups, which, for the next 79 days, received either unfiltered boiled coffee (lipid content, 1.0 g/l), boiled and filtered coffee (0.02 g lipid/l), or no coffee. Serum total cholesterol levels rose by 0.42 mmol/l (16 mg/dl; 95% confidence interval [CI], 0.14-0.71), LDL cholesterol levels by 0.41 mmol/l (16 mg/dl; 95% CI, 0.16-0.66), and apolipoprotein B levels by 8.6 mg/dl (95% CI, 3.8-13.4) in those who consumed boiled coffee relative to those who consumed boiled and filtered coffee. Responses of triglycerides, high density lipoprotein cholesterol, and apolipoprotein A-I did not differ significantly among these groups. No significant effects on serum lipid levels were found in the boiled and filtered coffee-consuming group compared with those who drank no coffee. In subjects who drank boiled coffee, serum campesterol level, an indicator of cholesterol absorption, remained constant. The serum lathosterol level, an indicator of cholesterol synthesis, increased by 11% (p less than 0.05), but the lathosterol to cholesterol ratio did not change. We propose that paper filters of the type used for drip-filtered coffee retain the lipid present in boiled coffee and in that way remove the hypercholesterolemic factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Increased removal of beta-very low density lipoproteins after ethinyl estradiol is associated with increased mRNA levels for hepatic lipase, lipoprotein lipase, and the low density lipoprotein receptor in Watanabe heritable hyperlipidemic rabbits.
The mechanism by which ethinyl estradiol (EE) decreases the concentration of lipids in the d less than 1.019 g/ml fraction (beta-very low density lipoprotein [beta-VLDL]) of homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits was studied. Treatment with EE increased the activity of hepatic lipase (HL) twofold to threefold in postheparin plasma and in liver biopsies. Postheparin plasma and adipose tissue lipoprotein lipase (LPL) activities were also increased twofold to fourfold after EE. The effects of EE on HL and LPL activities were associated with a threefold to sixfold elevation in liver HL mRNA and a fourfold elevation in adipose tissue LPL mRNA steady-state levels, pointing to an effect of EE on HL and LPL gene transcription. EE also increased liver low density lipoprotein (LDL) receptor mRNA levels threefold to fivefold. These results suggest a concerted action of LPL, HL, and the LDL receptor in the removal of beta-VLDL in homozygous WHHL rabbits with a defective LDL receptor. In addition, the content of apolipoprotein E in the d less than 1.019 g/ml fraction changed toward normal after EE. Because the remaining particles contained apolipoprotein B-100 almost exclusively, it is likely that apolipoprotein E-containing beta-VLDLs are preferentially removed. This may be the result of the increased activity of LPL and HL influencing the conformation of apolipoprotein E on the beta-VLDL particle in such a way that it is directly removed from the circulation, possibly by the induced LDL receptor.
Adipose Tissue↗
Plasma lipoproteins, apolipoproteins, and triglyceride metabolism in familial hypertriglyceridemia.
Several parameters of lipoprotein metabolism were examined in 38 men with primary hypertriglyceridemia (phenotype IV). Family investigation showed that 17 men had familial combined hyperlipidemia (FCH), seven had familial hypertriglyceridemia (FHT), and 14 had unclassified hypertriglyceridemia (UNC). In all three groups, plasma high density lipoprotein (HDL) cholesterol and the concentrations of apolipoprotein A-I and A-II were decreased, and apolipoprotein B was increased, each to the same extent. These results are compatible with an increased risk of cardiovascular disease in both FCH and FHT patients. The mean concentration of LDL cholesterol and the ratio of LDL to HDL cholesterol were significantly higher in FCH subjects, which could explain their increased risk. Postheparin lipoprotein lipase and hepatic lipase were the same in both groups. Determination of apolipoprotein C composition, which may modulate lipoprotein lipase activity, did not reveal any abnormalities in the different groups. In both FCH and FHT, the mean turnover rate of plasma triglycerides was almost twice normal, indicating that overproduction of plasma triglyceride plays an important role in both disorders. However, there was an overlap with normal controls, indicating impaired triglyceride removal in some subjects. The underlying mechanism of hypertriglyceridemia in FCH and FHT therefore seems to be heterogeneous.
Aged↗
Low density lipoprotein subfractions and relationship to other risk factors for coronary artery disease in healthy individuals.
By a recently developed sensitive density gradient ultracentrifugation method, the distribution of low density lipoprotein (LDL) subfractions was studied in the serum of healthy blood donors (20 to 62 years old). For each subject, we observed a specific LDL subfraction distribution characterized by the relative contribution of the three major LDL subfractions, LDL-1 (1.020 to 1.028 g/ml), LDL-2 (1.027 to 1.034 g/ml), and LDL-3 (1.033 to 1.039 g/ml), to total LDL. Statistical analysis was performed by using the LDL density variable defined as: (% of LDL-1) x 1.024 + (% of LDL-2) x 1.0305 + (% of LDL-3) x 1.036 as a continuous variable. Controlling for age, smoking habits, relative body weight and, when appropriate, for gender, it appeared that: 1) dense LDL subfraction patterns characterized by a predominant LDL-3 subfraction and a decreased LDL particle size were more likely to be found among men than among women, 2) with increasing density of LDL, the levels of serum triglycerides increased, whereas the concentration of HDL cholesterol and the ratio of LDL cholesterol to LDL apolipoprotein (apo) B decreased, and 3) the best model with significant contribution in the prediction of the LDL subfraction distribution was the three-variable model: total cholesterol, serum triglycerides, and LDL apo B (R2 = 0.40), whereas the best two-variable model consisted of serum triglycerides and high density lipoprotein cholesterol (R2 = 0.37). These data are consistent with results from a study described previously in which a different approach based on LDL subfraction quantification by gradient gel electrophoresis of whole plasma was used.
Adult↗
Effects of peritoneal dialysis with an overnight icodextrin dwell on parameters of glucose and lipid metabolism.
OBJECTIVE: To examine whether a reduced daily glucose load by overnight application of the less-absorbed glucose polymer icodextrin would have favorable effects on lipid profiles of continuous ambulatory peritoneal dialysis (CAPD) patients. STUDY DESIGN: Randomized crossover study with two subsequent periods of 6 weeks. SETTING: Home PD unit of a secondary-care hospital. PATIENTS: Twenty-one nondiabetic CAPD patients (15 male, 6 female; mean age 50.3+/-11.8 years). INTERVENTION: Participants were randomly assigned to receive an overnight dwell with either standard glucose solution or with a 7.5% icodextrin-containing solution. MAIN OUTCOME MEASURES: Relation between reduction in the total amount of intraperitoneal infused glucose and parameters of glucose (plasma glucose, insulin, and HbA1C) and lipid metabolism [free fatty acids, plasma lipids, lipoproteins, and low density lipoprotein (LDL) subfraction profile]. RESULTS: After the icodextrin dwells, a reduction of plasma total cholesterol (from 5.43+/-0.85 to 4.86+/-0.70 mmol/L, p < 0.001) and LDL cholesterol (from 3.38+/-0.87 to 2.93+/-0.73 mmol/L, p = 0.001) was observed. Also, high density lipoprotein (HDL) cholesterol (from 0.95+/-0.27 to 0.90+/-0.24 mmol/L, p = 0.029) was reduced, but the plasma total cholesterol-to-HDL ratio remained similar. Plasma free fatty acids and triglyceride levels tended to decrease (from 0.16+/-0.10 to 0.13+/-0.08 mmol/L, p= 0.06, and from 2.14+/-1.96 to 1.92+/-1.03 mmol/L, respectively). Evaluation of LDL subfraction profiles after ultracentrifugation showed a more buoyant LDL subfraction profile with fewer dense LDL particles in 6 patients and no changes in 14 patients after icodextrin. The effects on lipids were not accompanied by a decrease in fasting plasma glucose (from 5.76+/-1.29 to 5.86+/-0.80 mmol/L) or insulin levels (from 19.5+/-14.4 to 20.3+/-13.0 mU/L). CONCLUSION: These results suggest a beneficial effect on lipid profiles of CAPD patients with the use of an overnight dwell with icodextrin.
Cross-Over Studies↗