Lipoproteins, apolipoproteins, and low-density lipoprotein size among diabetics in the Framingham offspring study

Diabetes mellitus has been shown to be associated with lipid abnormalities. Prior studies have indicated that women with diabetes have a risk of coronary heart disease similar to that of men. We compared lipid parameters in diabetic and nondiabetic participants in cycle 3 of the Framingham Offspring Study. Values for plasma total cholesterol (TC), triglyceride, lipoprotein, cholesterol, apolipoprotein (apo) A1, B, apo and lipoprotein(a) [Lp(a)] and low-density lipoprotein (LDL) particle size were analyzed in 174 diabetic and 3,757 nondiabetic subjects. Data from a total of 2,025 men and 2,042 women participating in the third examination (1983 to 1987) of the Framingham Offspring Study were subjected to statistical analysis. Male and female diabetics showed lower high-density lipoprotein (HDL) cholesterol, higher triglycerides, higher very-low-density lipoprotein (VLDL) cholesterol, lower apo A1, and higher LDL particle scores, indicating smaller size, than nondiabetics. Female diabetics also showed significantly higher TC and apo B values than nondiabetics. The results remained statistically significant after controlling for obesity and menopausal status. The presence of small dense LDL particles (pattern B) was highly associated with diabetes and hypertriglyceridemia in both sexes, and the relative odds for pattern B remained significant in women but not in men after adjustment for age and hypertriglyceridemia. No differences in apo E isoform distribution were found for diabetics and nondiabetics. Diabetes was not associated with elevated LDL cholesterol levels. In conclusion, diabetics have lower HDL cholesterol and higher triglyceride levels and are more likely to have small dense LDL particles. Diabetes is not a secondary cause of elevated LDL cholesterol. Lipid screening of diabetics should include full quantification of lipids for proper assessment of potential atherosclerotic risk.     

Pregnancy in a patient with homozygous familial hypercholesterolemia undergoing low-density lipoprotein apheresis by dextran sulfate adsorption

Pregnancy and delivery in homozygous familial hypercholesterolemic (HFH) patients is extremely rare. We describe the case of a woman with HFH treated with low-density lipoprotein (LDL) apheresis by dextran sulfate adsorption who became pregnant and reached delivery uneventfully. LDL apheresis was performed biweekly, and lipoprotein analyses in pre-apheresis samples showed progressive increases in triglyceride, total cholesterol, and apolipoprotein (apo) B plasma concentrations. The fractional catabolic rate (FCR) for LDL cholesterol, as estimated by the first-order disappearance constants (k values) of the recovery of LDL cholesterol concentration to basal values after each apheresis session, increased more than threefold from week-24 to week-4 (labor is considered as time 0). After delivery basal values were recovered, but normalization was slower for LDL cholesterol than for the other lipidic parameters. High-density lipoprotein (HDL) showed a different pattern: HDL3 remained stable throughout gestation, whereas HDL2 cholesterol and apo A-I had a maximum at midgestation, then declined, and finally increased again at late gestation. With the exception of this latter increase of HDL2, all the other changes in lipoprotein concentrations during pregnancy and postpartum were similar to those found in healthy women. Thus, LDL apheresis does not interfere with physiologic adaptations of lipoprotein metabolism during pregnancy in HFH patients.     

Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT)

OBJECTIVES: To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors of myocardial infarction could be retarded by bezafibrate treatment. METHODS: A total of 92 dyslipoproteinemic men who had survived a first myocardial infarction before the age of 45 years were randomly assigned to treatment for 5 years with bezafibrate (200 mg three times daily) or placebo; 81 patients underwent baseline and at least one post-treatment coronary angiography. RESULTS: In addition to the decrease in very low density lipoprotein (VLDL) cholesterol (-53%) and triglyceride (-46%) and plasma apolipoprotein (apo) B (-9%) levels, bezafibrate treatment resulted in a significant increase in high density lipoprotein-3 (HDL3) cholesterol (+9%) level and a shift in the low density lipoprotein (LDL) subclass distribution toward larger particle species (peak particle diameter +032 nm). The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter (r=-0.23, p < 0.05), and percent (%) stenosis (r = 0.30, p < 0.01), respectively. Decreases in small dense LDL and/or VLDL lipid concentrations were unrelated to disease progression. CONCLUSIONS: Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins.     

Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome

Obesity is associated with dyslipidaemia characterised by increased fasting triglyceride and decreased high-density lipoprotein (HDL) concentrations. Causes for obesity-associated dyslipidaemia include insulin resistance, excessive caloric intake, increased free fatty acid production and disturbances in the counter-regulatory hormones. We examined the relationships between lipid parameters and obesity before and after adjustment of insulin resistance in 902 Hong Kong Chinese men. After adjustment for age, smoking and insulin resistance, increasing body mass index (BMI) and waist-to-hip ratio (WHR) remained closely associated with increased concentrations of triglyceride and apolipoprotein B (apo B), increased ratios between low-density lipoprotein (LDL) and HDL (LDL/HDL), and that between apo B and LDL (apo B/LDL), increased fasting and 2-h plasma glucose and insulin, as well as decreased concentrations of HDL, HDL2 and apolipoprotein A-I (apo A-I). On stepwise multiple regression analysis using age, BMI, WHR, insulin resistance and fasting plasma glucose as independent variables, BMI and WHR were the major determinants for the variance of triglyceride, HDL and its subfractions, LDL/HDL, apo B and apo B/LDL. Age was the most important predictor for total cholesterol and LDL. Insulin resistance only explained less than 1% of the variance in triglyceride and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR. In conclusion, obesity is associated with dyslipidaemia in Chinese men, characterised by increased plasma triglyceride, apo B, LDL/HDL, apo B/LDL, and decreased HDL, HDL2 and apo A-I concentrations. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia.     

The nature of the association between diet and serum lipids in the community: A twin study.

Diet is commonly thought to be an environmental influence on serum lipid concentrations. This study evaluated whether total caloric and fat intake predict total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TRIG) concentrations for environmental, as compared with genetic, reasons among 137 monozygotic and 67 dizygotic young adult twins. When genetic influences were controlled by correlating differences between monozygotic co-twins, a significant association remained between diet and TC, LDL, and HDL, suggesting that these dietary and serum lipid measures correlate for environmental reasons. Twin structural equation modeling confirmed these results. Overall, these results provide additional support for the hypothesis that diet is an environmental influence on TC, LDL, and HDL. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of low density and high density lipoproteins isolated from non-insulin dependent diabetic patients on prostaglandin secretion by mouse macrophage cell line P388D1

We have previously shown that low-density (LDL) and high-density (HDL) lipoprotein from healthy subjects can promote in vitro prostaglandin (PG) release by murine macrophages. In this pilot study, we have measured PG production induced by lipoproteins of six diabetic patients with poor metabolic control, compared to five healthy controls. Plasma lipoprotein levels were similar in both groups. Lipoprotein fractions were purified by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and PG quantified by HPLC. In presence of LDL, in control subjects, there was an increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic patients, the secretion pattern was similar. In presence of HDL, in control subjects, total PG secretion was also increased, but it was balanced between TxB2 and prostacyclin. In diabetic patients, at low HDL concentration (10 mg/l) the secretion was mainly due to TxB2, while at higher HDL concentrations (100 mg/l). the secretion was balanced between TxB2 and prostacyclin. Comparison of means of areas under curve for the two groups studied showed that LDL increased all PG secretion in diabetic patients compared to controls (P < 0.05 for PGF2alpha), while HDL increased all PG secretion in controls compared to diabetic patients, except PGF2alpha. Our work suggests a key role of LDL in TxB2 secretion in diabetic patients, which is a major proaggregant and vasoconstrictive agent. There was also an increased secretion of all PG in diabetic patients.     

The accuracy and precision of four infrared aural canal thermometers during cardiac surgery

Hormone replacement therapy has been shown to decrease the risk of coronary heart disease (CHD) in menopausal women. In this cross-sectional study, we addressed the following question: What effects would combined oral hormone replacement therapy have on plasma lipid and lipoprotein profiles independent of the other known CHD risk factors? We analyzed the plasma lipoproteins of two groups of menopausal women who were randomly selected from a large database of individuals. One group (n = 10) was not taking any hormone replacement therapy (NO HRT), while the second group (n = 8) was taking a daily dose of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone orally (PremPro, Wyeth-Ayerst, Philadelphia, PA) for at least 6 months (HRT). The two groups were not different in age, body weight, percent body fat, body mass index (BMI), waist to hip ratio, blood pressure, or insulin and glucose levels. High-density lipoprotein (HDL)-cholesterol was significantly higher (P < .05) in the HRT group. The total cholesterol (TC) to HDL-cholesterol ratio was significantly lower for HRT versus NO HRT (P < .05). Apolipoprotein (apo) A-1, the apo A-1/B ratio, and lecithin:cholesterol acyltransferase (LCAT) activity were significantly higher in HRT (P < .05). Lipoprotein subclass profiles measured by nuclear magnetic resonance (NMR) spectroscopy showed an increase in larger HDL subpopulations (H3 and H4) in HRT (P < .05), which are considered antiatherogenic. No differences were seen in the cholesterol concentration or size of low-density lipoprotein (LDL) subpopulations in HRT compared with NO HRT. These results indicate that the combined estrogen and progesterone treatment leads to beneficial effects on plasma lipoproteins. The beneficial effects include (1) increases in HDL-cholesterol and predominance of HDL2, (2) no adverse effects on LDL subpopulation distribution, and (3) increases in apo A-1 levels and LCAT activity, which indicate an improvement in reverse cholesterol transport.     

Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes

The risk of coronary heart disease (CHD) is lower in women than in men, but increases in women after menopause. Some of the gender, age, and menopausal-related differences in CHD risk may relate to differences in lipoprotein subspecies. We therefore examined these subspecies in three groups of healthy subjects: premenopausal women (W, n = 72, mean age 41.2 +/- 6.5), postmenopausal women (PMW, n = 74, 55.8 +/- 7.4), and men (M, n = 139, 48.8 +/- 10.7). We measured plasma levels of lipids, lipoprotein cholesterol, apolipoproteins A-I, A-IV, B, C-III, and E, and lipoprotein subspecies Lp A-I, Lp A-I:A-II, Lp B, Lp B:C-III, and Lp B:E, as well as LDL and HDL particle sizes. Our data indicate that women have significantly higher values of HDL-C, apoA-I, apoE, and Lp A-I; larger LDL and HDL particle sizes; and lower values of triglyceride, apoB, and Lp B:C-III particles than men, with no difference in Lp A-I:A-II. Postmenopausal status was associated with significantly higher values of total cholesterol, triglyceride, VLDL-C, and LDL-C; increased levels of apoB, C-III, and E; elevated values of Lp B, Lp B:C-III, and Lp B:E; and lower levels of HDL-C along with smaller HDL particle size. Moreover, we noted a strong correlation between LDL and HDL particle size. Our data are consistent with the concepts that male gender confers decreases in HDL subspecies due to lower Lp A-I levels; while postmenopausal status results in higher levels of all apoB-containing lipoproteins (Lp B, Lp B:C-III, and Lp B:E). The lipoprotein alterations associated with male gender and postmenopausal status would be expected to increase CHD risk.     

Associations between acute lipid stress responses and fasting lipid levels 3 years later.

The authors assessed the association between lipid responses to acute mental stress and fasting serum lipid levels 3 years later in 199 middle-aged men and women. Total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol increased following moderately stressful behavioral tasks. LDL cholesterol, HDL cholesterol, and total:HDL ratio measured 3 years later were predicted by acute stress responses independent of gender, age, socioeconomic position, change in body mass, smoking, alcohol consumption, or hormone replacement therapy baseline lipid levels. The odds of clinically elevated cholesterol were significantly greater in the highest compared with the lowest stress tertile, independent of baseline levels and covariates. Acute lipid stress responsivity may reflect processes that contribute to the development of elevated blood cholesterol concentration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer

PURPOSE: To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.     

Modifications in high-density lipoprotein lipid composition and structure alter the plasma distribution of free and liposomal annamycin

Recent studies have shown that changes in lipoprotein cholesterol and triglyceride concentration alters the plasma distribution of free (Ann.) and liposomal annamycin (LAnn) and that the majority of Ann. is associated with high-density lipoproteins (HDL) following the incubation in plasma of LAnn. To demonstrate that alterations in HDL lipid composition and HDL structure may influence the plasma distribution of Ann. and LAnn, Ann. and LAnn (20 micrograms/mL) were incubated in plasma pretreated with dithionitrobenzoate (DTNB, a compound which inhibits the conversion of free cholesterol to esterified cholesterol) 18 h prior to the experiment or in untreated plasma for 60 min at 37 degrees C. In addition, Ann. and LAnn were co-incubated with DTNB in plasma for 60 min at 37 degrees C. Following incubation the plasma was separated into its HDL, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and lipoprotein-deficient plasma (LPDP) fractions by ultracentrifugation and assayed for Ann. by fluorimetry. The HDL plasma cholesterol:triglyceride concentration ratio was significantly decreased following 18 h of DTNB pretreatment compared to untreated plasma controls. No significant differences in LDL/VLDL plasma cholesterol:triglyceride concentration ratio following 18 h of DTNB pretreatment was observed. An increased number of discoidal HDL particles were observed following 18 h of DTNB pretreatment. When Ann. was incubated in plasma pretreated with DTNB for 18 h the percentage of Ann. recovered in the HDL, LDL, and VLDL fractions significantly increased. However, the percentage of Ann. recovered within the LPDP fraction was significantly decreased. When LAnn was incubated in plasma pretreated with DTNB for 18 h the percentage of Ann. recovered in the HDL fraction significantly decreased. The percentage of Ann. recovered in the LPDP fraction significantly increased when LAnn was incubated in plasma pretreated with DTNB for 18 h. No significant differences in Ann. lipoprotein distribution were observed when Ann. and LAnn were co-incubated with DTNB in plasma for 1 h. These findings suggest that the cholesterol:triglyceride concentration ratio and physical structure of HDL maybe important in defining the capacity of HDL to sequester Ann.     

NeuroD regulates multiple functions in the developing neural retina in rodent

Platelet-activating factor acetylhydrolase (PAF-AH) is transported by lipoproteins in plasma and is thought to possess both anti-inflammatory and anti-oxidative activity. It has been reported that PAF-AH is recovered primarily in small, dense LDL and HDL following ultracentrifugal separation of lipoproteins. In the present studies, we aimed to further define the distribution of PAF-AH among lipoprotein fractions and subfractions, and to determine whether these distributions are affected by the lipoprotein isolation strategy (FPLC versus sequential ultracentrifugation) and LDL particle distribution profile. When lipoproteins were isolated by FPLC, the bulk (approximately 85%) of plasma PAF-AH activity was recovered within LDL-containing fractions, whereas with ultracentrifugation, there was a redistribution to HDL (which contained approximately 18% of the activity) and the d>1.21 g/ml fraction (which contained approximately 32%). Notably, re-ultracentrifugation of isolated LDL did not result in any further movement of PAF-AH to higher densities, suggesting the presence of dissociable and nondissociable forms of the enzyme on LDL. Differences were noted in the distribution of PAF-AH activity among LDL subfractions from subjects exhibiting the pattern A (primarily large, buoyant LDL) versus pattern B (primarily small, dense LDL) phenotype. In the latter group, there was a relative depletion of PAF-AH activity in subfractions in the intermediate to dense range (d=1.039-1.047 g/ml) with a corresponding increase in enzyme activity recovered within the d>1.21 g/ml ultracentrifugal fraction. Thus, there appears to be a greater proportion of the dissociable form of PAF-AH in pattern B subjects. In both populations, most of the nondissociable activity was recovered in a minor small, dense LDL subfraction. Based on conjugated dienes as a measure of lipid peroxidation, variations in PAF-AH activity appeared to contribute to variations in oxidative behavior among ultracentrifugally isolated LDL subfractions. The physiologic relevance of PAF-AH dissociability and the minor PAF-AH-enriched oxidation-resistant LDL subpopulation remains to be determined.     

Differences in lipoprotein lipid concentration and composition modify the plasma distribution of cyclosporine

PURPOSE: The purpose of this study was to define the relationship between lipoprotein (LP) lipid concentration and composition and the distribution of cyclosporine (CSA) in human plasma. METHODS: 3H-CSA LP distribution was determined in normolipidemic human plasma that had been separated into different LP and lipoprotein-deficient plasma (LPDP) fractions by either affinity chromatography coupled with ultracentrifugation, density gradient ultracentrifugation or fast protein liquid chromatography. 3H-CSA LP distribution (at a concentration of 1000 ng/ml) was also determined in patient plasma samples with defined dyslipidemias. Furthermore, 3H-CSA LP distribution was determined in patient plasma samples of varying LP lipid concentrations. Following incubation, the plasma samples were separated into their LP and LPDP fractions by sequential phosphotungistic acid precipitation in the dyslipidemia studies and by density gradient ultracentrifugation in the specific lipid profile studies and assayed for CSA by radioactivity. Total plasma and lipoprotein cholesterol (TC), triglyceride (TG) and protein (TP) concentrations in each sample were determined by enzymatic assays. RESULTS: When the LP distribution of CSA was determined using three different LP separation techniques, the percent of CSA recovered in the LP-rich fraction was greater than 90% and the LP binding profiles were similar with most of the drug bound to plasma high-density (HDL) and low-density (LDL) lipoproteins. When 3H-CSA was incubated in dyslipidemic human plasma or specific patient plasma of varying LP lipid concentrations the following relationships were observed. As the very low-density (VLDL) and LDL cholesterol and triglyceride concentrations increased, the percent of CSA recovered within the VLDL and LDL fractions increased. The percent of CSA recovered within the HDL fraction significantly decreased as HDL triglyceride concentrations increased. The percent of CSA recovered in the LPDP fraction remained constant except in hypercholesterolemic/hypertriglyceridemic plasma where the percent of CSA recovered decreased. Furthermore, increases in VLDL and HDL TG/TC ratio resulted in a greater percentage of CSA recovered in VLDL but less in HDL. CONCLUSIONS: These findings suggest that changes in the total and plasma LP lipid concentration and composition influence the LP binding of CSA and may explain differences in the pharmacological activity and toxicity of CSA when administered to patients with different lipid profiles.     

Relationship between acute diarrhoea and low plasma levels of vitamin A and retinol binding protein

OBJECTIVE: We studied possible sex differences of the effect of fenofibrate on serum lipoproteins. Twenty-three patients with primary hypercholesterolaemia (10 postmenopausal women and 13 aged-matched men) were treated with slow-release fenofibrate for 96 weeks. RESULTS: Steady state lipoprotein concentrations were reached after 12 and 24 weeks of treatment in women and men, respectively. During the subsequent follow-up the lipoprotein concentrations remained constant. In women total and low-density lipoprotein (LDL) cholesterol decreased from 299 to 234 mg.dl-1 and from 210 to 151 mg.dl-1, respectively, and in men from 265 to 233 mg.dl-1 and from 192 to 160 mg.dl-1. The decrease in triglycerides was also more pronounced in women (-42%) than in men (-18%). High-density lipoprotein (HDL) cholesterol increased significantly in women from 53 to 63 mg.dl-1 but not in men (45 to 50 mg.dl-1). Since the changes in LDL and HDL cholesterol occurred in opposite directions, the decrease in LDL/HDL cholesterol ratio was accentuated in both groups. However, this ratio was decreased almost twofold in women (-41%) compared to men (-23%). Although the serum concentrations of fenofibric acid were 1.3-fold higher in women than in men, which was probably due to the higher body weight in men (1.2-fold), this difference can hardly explain the favorable effect on lipoproteins in women. CONCLUSION: The present study indicates that fenofibrate might be very effective by reducing the concentrations of atherogenic lipoproteins in postmenopausal women.     

The significance of lipoproteins in serum binding variations of propofol

The protein binding of propofol was investigated in vitro in isolated lipoprotein fractions (very low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) and in serum samples from the following subjects: healthy normolipemic volunteers (n = 16), hyperlipidemic subjects diagnosed with familiar polygenic hypercholesterolemia (n = 26) showing high levels of cholesterol, and elderly subjects (n = 15). Protein binding was determined by using ultrafiltration, and the concentration of unbound propofol was measured by using liquid chromatography. Levels of total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, HDL cholesterol, albumin, and alpha1-acid glycoprotein were also measured. Propofol was extensively bound to the three lipoprotein fractions (88%+/-2% to VLDL, 93%+/-1% to LDL, and 91%+/-4% to HDL). The percentage of unbound propofol was significantly decreased (P < 0.0001) in hyperlipidemic (0.88%+/-0.20%) individuals whose levels of cholesterol and triglycerides were increased versus healthy subjects (1.26%+/-0.22%), whereas no significant difference was found in the elderly group (1.12%+/-0.23%). A positive relationship was found between serum protein binding of propofol and lipid levels. Multiple regression analysis, including all subjects, showed that changes in the levels of total cholesterol and triglycerides explained approximately 62% of the variability in the serum protein binding of propofol. These results stress the importance of triglycerides and cholesterol in the serum protein binding of propofol. We therefore suggest that these variations in lipid levels, and consequently in protein binding, may influence anesthetic practice with propofol. IMPLICATIONS: We investigated the effect of serum lipids in the protein binding of propofol. We found that propofol binds extensively to all lipoprotein fractions. Propofol binding showed a significant relationship with the serum levels of cholesterol and triglycerides.     

Strobilurin M, tetrachloropyrocatechol and tetrachloropyrocatechol methyl ether: new antibiotics from a Mycena species

OBJECTIVE: To describe lipid and lipoprotein perturbations in gestational diabetes mellitus (GDM) and to examine the potential consequences--e.g, increased birth weight and increased placental lipid transfer. STUDY DESIGN: Maternal and cord free fatty acids (FFAs) and total, very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) (and maternal HDL2 and HDL3), triglyceride (TG), and cholesterol and dietary intake were determined for women with diet-treated GDM and for healthy pregnant women with normal glucose tolerance. RESULTS: Women with GDM had higher hemoglobin A1c than controls, while body weight gain was significantly lower for women with GDM as compared to controls. Plasma and lipoprotein TG concentrations were greater for women with GDM, and although plasma FFAs were higher in women with GDM versus controls, the difference was not significant. No differences were observed between groups with respect to maternal plasma or lipoprotein cholesterol. Cord plasma and lipoprotein lipids were similar between groups; with the exception of VLDL + LDL TG, which was lower in women with GDM. In controls, there were significant correlations between maternal plasma TG and cord FFAs; maternal HDL2 cholesterol and cord plasma cholesterol; and maternal plasma TG, maternal HDL2 cholesterol, cord FFAs, and infant birth weight. In GDM, maternal plasma cholesterol and cord VLDL + LDL cholesterol correlated. There were no significant correlations between maternal or cord lipids and infant birth weight in women with GDM. CONCLUSION: Hypertriglyceridemia, rather than hypercholesterolemia, is a feature of GDM. However, elevations in maternal plasma and lipoprotein TGs in women with GDM were not related to fetal lipid concentrations or infant birth weight.     

Initial clinical experience with the Ahmed Glaucoma Valve implant in pediatric patients

There is evidence that a low-density lipoprotein (LDL) subfraction profile of increased concentrations of small, dense LDL particles is less common among trained than among sedentary normocholesterolemic men, but it is still uncertain whether there is a similar association in hypercholesterolemia also. Therefore, we determined the lipid and apolipoprotein concentration and composition of six LDL subfractions (density gradient ultracentrifugation) in 20 physically fit, regularly exercising (>three times per week) hypercholesterolemic men and 20 sedentary hypercholesterolemic controls. Trained (maximal oxygen consumption [VO2max], 57.3 +/- 7.4 mL/kg/min) and sedentary (VO2max, 37.5 +/- 8.8 mL/kg/min) individuals (aged 35 +/- 11 years; body mass index [BMI], 23.9 +/- 2.7 kg/m2) were matched for LDL apolipoprotein (apo) B levels (108 +/- 23 and 112 +/- 36 mg/dL, respectively). Trained subjects had significantly lower serum triglyceride (P < .05) and very-low-density lipoprotein (VLDL) cholesterol levels (P < .05) and higher high-density lipoprotein 2 (HDL2) cholesterol levels (P < .01) than sedentary controls. LDL particle distribution showed that trained individuals had significantly less small, dense LDL (d = 1.040 to 1.063 g/mL) and more large LDL (d = 1.019 to 1.037 g/mL) subfraction particles than sedentary controls, despite equal total LDL particle number. Analysis of LDL composition showed that LDL particles of hypercholesterolemic trained men had a higher free cholesterol content than LDL of untrained hypercholesterolemic men. Small, dense LDL in hypercholesterolemic trained men were richer in phospholipids than those in sedentary controls. These data demonstrate the significant influence of aerobic fitness on lipoprotein subfraction concentration and composition, thereby emphasizing the role of exercise in the treatment and risk reduction of hypercholesterolemia.     

Characterization of a composite gradient gel for the electrophoretic separation of lipoproteins

We describe a protocol for making a new type of gradient gel, the Composite gradient gel, that was designed to resolve plasma lipoproteins using nondenaturing gradient gel electrophoresis. The new gel format allows analysis both of high density lipoproteins (HDLs) and low density lipoproteins (LDLs) on the same gel. The gel gave highly repeatable (r2 = 0.999) size estimates. We compared lipoprotein phenotypes determined from the new gradient gel with those obtained using specialized HDL and LDL gradient gels. The comparisons indicated that the Composite gel gave lipoprotein particle size estimates for HDLs and LDLs that were virtually identical to those obtained, respectively, from the specialized HDL and LDL gradient gels. We measured median diameters, which reflect the distributions of absorbance, for LDLs and for HDLs and found that the Composite gel gave lipoprotein size distributions that were virtually identical to those measured using the specialized LDL and HDL gels. Finally, comparison of fractional absorbance for six lipoprotein size intervals obtained from the Composite and specialized gels revealed a close correlation (r2 = 0.828). Thus, it appears that both LDL and HDL size phenotypes may be evaluated simultaneously using a single gradient gel format.     

An experience of lipoprotein (a) dosage in a Moroccan population of 184 subjects

One hundred and eighty-four patients underwent complete lipid analysis (total cholesterol, HDL and LDL cholesterol, triglycerides, apolipoproteins A1 and B, lipoprotein (a)) and coronary angiography, in order to evaluate the discriminant value of the lipoprotein (a). Subjects with non-significant coronary stenoses (< 50% of the lumen) were used as a control group (n = 84). The others were considered to be pathological. The total cholesterol, HDL cholesterol and triglycerides were measured by an enzymatic colorimetric method. The LDL cholesterol was calculated by Friedewald's formula. The apolipoprotein A1 and B were measured by immunoturbidimetry and the lipoprotein (a) by an Elisa. The results showed a relationship between the different lipid levels, especially between high lipoprotein (a), and the severity of the coronary disease. A quantitative and qualitative study showed no significant influence of the other risk factors on the mean lipoprotein (a) level. Gender and age had no influence. Therefore, the higher the lipoprotein (a) level, the greater was the coronary risk, independently of the other associated risk factors.     

Linkage of low-density lipoprotein size to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency

Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within-genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus.