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.     

Biological variability in serum vitamin E concentrations: relation to serum lipids

The components of biological variation in serum vitamin E in relation to serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), apolipoprotein A-I (apo A-I), and apo B were examined in 26 healthy volunteers who had monthly blood samplings during one calendar year. The estimated CVs for vitamin E were: interindividual, 19.9%, and intraindividual, 11.9%; the index of individuality (I-index) was 0.59. The I-indices for all lipid variables were < 0.51. Serum concentrations of vitamin E, cholesterol, triglycerides, HDL-C, LDL-C, and apo B were lower in spring than in the other seasons. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were for vitamin E 14.5%, cholesterol 16.2%, triglycerides 14.5%, and LDL-C 24.3%. A significant common annual rhythm was expressed in vitamin E or lipid variables and in the changes in ambient temperature the weeks before blood sampling (inverse relations). There were highly significant positive time relations between serum vitamin E and cholesterol, triglycerides, and apo B. Subjects with higher homeostatic setpoints of cholesterol showed higher homeostatic setpoints of vitamin E, triglycerides, LDL-C, and apo B.     

Lack of relations of hostility, negative affect, and high-risk behavior with low plasma lipid levels in the Coronary Artery Risk Development in Young Adults Study

BACKGROUND: Previous studies have suggested that low plasma cholesterol levels or cholesterol lowering may increase the risk of suicide and violent death. Increased aggression, risk-taking behavior, or depression has been associated with low cholesterol levels in some studies. METHODS: A total of 4240 subjects of the Coronary Artery Risk Development in Young Adults study, aged 23 to 35 years, were included in the study. Analyses were stratified by race (black or white) and sex. Persons in the lowest 10% of plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were compared with the other participants in each race/sex group, using standardized measures of hostility, anger suppression, depressive symptoms, and anxiety. The relations between 5-year change in hostility and 5-year change in lipid levels also were examined. The relations between lipid levels and high-risk behavior (e.g., violent arguments or having a gun at home) were examined in a subset of subjects. All analyses were adjusted for relevant covariates. RESULTS: In cross-sectional analyses, low total cholesterol levels were not related to any of the psychological measures in any race/sex group. Among black women only, low low-density lipoprotein cholesterol was related to greater anxiety, and low triglycerides were related to lower anger suppression (P < or = .002). Among white men only, increases in hostility during the 5-year follow-up were related to increases in triglycerides (P < .01), but changes in hostility were unrelated to changes in cholesterol levels. Among a subset of 371 subjects with initially elevated total cholesterol (> or = 5.17 mmol/L [> or = 200 mg/dL]) and a non-medicated decrease of 0.52 mmol/L (> or = 20 mg/dL) or more during 5 years, hostility decreased in a univariate analysis (P < .001). High-risk behaviors also were not associated with low lipid levels. CONCLUSION: The results do not support a consistent relation between hostility, negative affect, or high-risk behaviors with low lipid levels or lipid-lowering among young adults.     

Comparative effects of atenolol versus celiprolol on serum lipids and blood pressure in hyperlipidemic and hypertensive subjects

Antihypertensive drugs may affect serum lipoprotein levels in mixed populations but data in hyperlipidemic patients are scanty. Atenolol versus celiprolol effects on serum lipoproteins were compared in 159 hyperlipoproteinemic hypertensive patients. This was a randomized, double-blind, parallel-group, positive-controlled multicenter trial with centralized lipoprotein laboratory and diet constancy monitoring. Blood pressure reduction and serum lipoprotein and apoprotein levels were monitored for 3 months. Both drugs reduced systolic and diastolic blood pressures. Atenolol had greater effects than celiprolol on diastolic pressure, but effects on systolic blood pressure were not different. Patients receiving atenolol had lower serum high-density lipoprotein cholesterol levels and higher low-density lipoprotein/high-density lipoprotein cholesterol ratios, whereas patients treated with celiprolol showed no contrasting changes. These differences in lipoprotein levels between drug treatment groups were statistically significant at weeks 9 and 12. The difference between drug treatments was also significant if the values of the 9- and 12-week visits were averaged. Patients taking atenolol had statistically significantly higher serum levels of total cholesterol, triglycerides and apoprotein B at 9 weeks. These divergent directional changes were consistent throughout and statistically significantly different between drugs.     

Estrogen improves endothelial function

PURPOSE: To determine the effect of estrogen on endothelium-dependent relaxation in the cutaneous microcirculation of women. METHODS: Three groups of women participated in the study. Group 1 (n = 20) was premenopausal and had a mean age of 39 years (range 24-50 years). Group 2 (n = 9) was postmenopausal and had a mean age of 58 years (range 53-65 years). Group 3 (n = 11) was postmenopausal and taking estrogen replacement therapy; the mean age was 53 years (range 43-58 years). Eleven women in group 1 underwent testing twice, once during menstruation (mean serum estradiol level 73 +/- 30 pg/ml) and once during midcycle (mean serum estradiol level 268 +/- 193 pg/ml; p = 0.003). Single-point laser Doppler ultrasound and laser Doppler imaging with a scanner were used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium-independent smooth muscle relaxant). RESULTS: All three groups were matched for body mass index and fasting glucose, total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglyceride levels. All women had normal blood pressure, and none smoked. Mean serum estradiol levels were 196 +/- 170 pg/ml (group 1), 35 +/- 12 pg/ml (group 2), and 107 +/- 78 pg/ml (group 3) (p = 0.004). Maximum microvascular vasodilatation (percentage increase over baseline) in response to acetylcholine was reduced in group 2 (93% +/- 43%) compared with group 1 (187% +/- 63%) and group 3 (142% +/- 56%) (p = 0.001). The response to sodium nitroprusside also was diminished in group 2 (73% +/- 27%) compared with group 1 (126% +/- 45%) and group 3 (100% +/- 32%) (p = 0.02). Within group 1 the acetylcholine response was higher during the midcycle phase (186% +/- 31%) compared with the menstrual phase (147% +/- 57%) (p < 0.05). The sodium nitroprusside response also was higher during the midcycle phase (144% +/- 31%) compared with the menstrual phase (94% +/- 41%) (p < 0.05) CONCLUSION: The results indicate that estrogens might enhance endothelium-dependent and endothelium-independent vasodilatation in the microcirculation of women.     

Low lipid concentrations in critical illness: implications for preventing and treating endotoxemia

OBJECTIVES: To determine the prevalence and clinical significance of hypolipidemia found in critically ill patients, and whether the addition of a reconstituted lipoprotein preparation could inhibit the generation of tumor necrosis factor-alpha (TNF-alpha) in acute-phase blood taken from these patients. SETTING: Surgical intensive care unit (ICU) of a large urban university hospital. DESIGN: Prospective case series. PATIENTS: A total of 32 patients with a variety of critical illnesses had lipid and lipoprotein concentrations determined. Six patients and six age- and gender-matched control subjects had whole blood in vitro studies of the effect of lipoprotein on lipopolysaccharide mediated TNF-alpha production. INTERVENTIONS: Blood samples were drawn on admission to the ICU and over a subsequent 8-day period. MEASUREMENTS AND MAIN RESULTS: Mean serum lipid and lipoprotein values obtained from patients within 24 hrs of transfer to the surgical ICU were extremely low: mean total cholesterol was 117 mg/dL (3.03 mmol/L), low-density lipoprotein cholesterol 71 mg/dL (1.84 mmol/L), and high-density lipoprotein cholesterol 25 mg/dL (0.65 mmol/L). Only the mean triglyceride concentration of 105 mg/dL (1.19 mmol/L), and the mean lipoprotein(a) concentration of 25 mg/dL (0.25 g/L) were within the normal range. During the first 8 days following surgical ICU admission, there were trends toward increasing lipid and lipoprotein concentrations that were significant for triglycerides and apolipoprotein B. Survival did not correlate with the lipid or lipoprotein concentrations, but patients with infections had significantly lower (p = .008) high-density lipoprotein cholesterol concentrations compared with noninfected patients. Lipopolysaccharide-stimulated production of TNF-alpha in patient and control blood samples was completely suppressed by the addition of 2 mg/mL of a reconstituted high-density lipoprotein preparation. CONCLUSIONS: Patients who are critically ill from a variety of causes have extremely low cholesterol and lipoprotein concentrations. Correction of the hypolipidemia by a reconstituted high-density lipoprotein preparation offers a new strategy for the prevention and treatment of endotoxemia.     

19-Allylaminoherbimycin A, an analog of herbimycin A that is stable against treatment with thiol compounds or granulocyte-macrophage colony-stimulating factor in human leukemia cells

OBJECTIVE: To investigate the effects on lipid and lipoprotein metabolism of two doses (5- or 10 micrograms/24 h) of levonorgestrel released from an intrauterine device (IUD) in combination with orally administered estradiol (2 mg estradiol valerate) in perimenopausal women. DESIGN: A 1-year prospective randomized single blind clinical trial. SETTING: Department of Obstetrics and Gynaecology, Ostra Hospital, G?teborg, Sweden. SUBJECTS: Fifty-one perimenopausal women with climacteric symptoms. OUTCOME MEASURES: Cholesterol in serum and in lipoprotein fractions; high-density lipoprotein (HDL), low-density lipoprotein (LDL). Triglycerides in serum and in very low-density lipoprotein. RESULTS: In both treatment groups significant elevations in HDL-cholesterol of similar magnitude were observed after 1 month and these changes were maintained during the 12 month observation period. In both treatment groups an initial significant decrease of LDL-cholesterol was observed and the decrement was maintained after 12 months. Serum levels of cholesterol decreased significantly in both groups after 1 month and were maintained after 12 months in the levonorgestrel-IUD (LNG-IUD) 5 micrograms group. However, the initial reduction of serum cholesterol in the LNG-IUD 10 micrograms group did not differ from baseline after 12 months. Serum triglyceride levels fluctuated during the observation period. No significant changes occurred. CONCLUSION: Continuous combined HRT with intrauterine administration of levonorgestrel, 5- or 10 micrograms/24 h, in perimenopausal women was observed to increase HDL-cholesterol and to decrease LDL-cholesterol compared with pretreatment values. The low doses of levonorgestrel did not reverse the beneficial effects on lipid metabolism usually seen after estradiol administration.     

Role for cell surface oligosaccharide in cell-cell recognition during implantation

OBJECTIVE: To evaluate the effect of three different dosages of transdermally administered 17beta-estradiol on serum lipoproteins in women who had recently experienced surgical menopause. MATERIAL AND METHODS: We undertook a 2-year, randomized, double-blind, placebo-controlled study in which 126 subjects were recruited and stratified by age, and 93 patients completed the protocol. Serum lipoproteins were assessed before initiation of treatment and after 12 and 24 months of therapy with 0.025, 0.05, or 0.1 mg of estradiol daily. RESULTS: Total serum cholesterol and low-density lipoprotein cholesterol showed dose-dependent decreases that reached statistical significance after 2 years of treatment with transdermally administered estradiol. CONCLUSION: This study confirms that transdermally administered 17beta-estradiol has a modest beneficial effect on serum lipoproteins, with decreased levels of total cholesterol and low-density lipoprotein cholesterol.     

Asymmetrical hemispheric activation and behavioral persistence: effects of unilateral muscle contractions

OBJECTIVE: To compare pubertal maturation, sex steroid hormones, and lipoproteins and their interrelationships in male offspring of parents with premature coronary heart disease (cases) and a control group. DESIGN: This was a cross-sectional comparison of cases and members of a control group 10 to 15 years of age. SUBJECTS AND METHODS: Offspring were recruited from patient lists of area physicians. Members of the control group were recruited from area schools. Body mass (kg/m2), serum lipids, lipoproteins, apolipoproteins, estradiol, and free testosterone were measured. RESULTS: Differences in age were not significant, but offspring were taller, heavier, and more mature. Offspring had higher total and low density lipoprotein cholesterol. Offspring had lower estradiol levels in early puberty but higher levels in late puberty. With family history and body mass in the regression models for lipid parameters, free testosterone was a significant explanatory factor for total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein, and estradiol was a significant predictor for apolipoprotein B. The percent of the variance in the lipid parameters explained by testosterone and estradiol was small. CONCLUSION: Sex hormone concentrations appear to be modest but significant predictors of lipoprotein and apolipoprotein concentrations in offspring and a control group in cross-sectional analysis. After controlling for pubertal maturation, hormone and lipid concentrations differed in offspring and the control group.     

Association of fasting plasma free fatty acid concentration and frequency of ventricular premature complexes in nonischemic non-insulin-dependent diabetic patients

We investigated the association between free fatty acid (FFA) concentration and ventricular premature complexes (VPCs) in nonischemic patients with non-insulin-dependent diabetes mellitus using 3 approaches: cross-sectional analysis (n = 142), intervention including induction of elevated FFA levels with Intralipid heparin (n = 15), and reduction in FFA levels with Acipimox (n = 34) and a longitudinal follow-up study (n = 59). Patients at the third tertile of fasting plasma FFA concentration had the strongest increase in VPCs. Independently of age, sex, body mass index (BMI), waist/hip ratio, left ventricular mass index, glycated hemoglobin, fasting plasma insulin and triglyceride concentration, and daily physical activity, FFA concentration and VPCs were significantly correlated (r = 0.21 p <0.01). At multiple logistic regression analysis independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, glycated hemoglobin, fasting plasma insulin, triglycerides and potassium concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity, plasma FFA concentration was a significant determinant of VPCs (odds ratio 1.2, 95% confidence interval 1.0 to 2.3). Intralipid infusion (10% in 24 hours) (n = 15) and acipimox administration (250 mg, 4 times/day) (n = 34) increased, and decreased fasting plasma FFA concentration, respectively. In those studies, change in VPCs paralleled the effects on plasma FFA. In the longitudinal study (n = 59), plasma FFA concentration predicted the development of VPCs (RR 1.4 95% confidence interval 1.0 to 1.9) independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, fasting plasma triglyceride concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity. In conclusion, in nonischemic patients with non-insulin-dependent diabetes mellitus, plasma FFA concentration is associated with the frequency of ventricular premature complexes.     

Antenatal steroids, condition at birth and respiratory morbidity and mortality in very preterm infants

The study purpose was to compare the effect of exercise training on serum lipid and apolipoprotein concentrations and the activities of intravascular enzymes related to lipid transport in previously untrained eumenorrheic, premenopausal (PRM) women (n = 21; mean age, 36 +/- 3 years) and estrogen-free postmenopausal (POM) women (n = 16; mean age, 68 +/- 8 years). Subjects trained at a progressive intensity and duration (50% to 75% maximal O2 consumption [VO2max], 200 to 300 kcal/session) 4 d/wk for 12 weeks. Before and after training, VO2max, body weight, relative body fat, and fasting blood samples were obtained following 2 weeks on a standardized diet designed to maintain body weight and during the early follicular stage for the PRM group. Blood samples were analyzed for serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), the cholesterol content of the HDL3 subfraction, apolipoprotein (apo)A-I and apoB, lipoprotein(a), and the activity of lecithin:cholesterol acyltransferase (LCAT). Total and hepatic triglyceride lipase activity (HTGLA) were determined from plasma samples obtained after heparin administration. The cholesterol content of the low-density lipoprotein (LDL) and HDL2 subfractions and endothelial-bound lipoprotein lipase activity (LPLA) were calculated. A two (group) x two (time) multivariate ANOVA (MANOVA), with repeated measures for time indicated that the exercise-induced changes in physiological measurements, serum lipid or apolipoprotein concentrations, or enzyme activities did not differ between groups. Serum concentrations of TC, LDL-C, and HDL3 cholesterol, TG, and apo A-I and apoB were higher in POM women compared with the PRM group (P < .05 for all). For the combined groups, body weight and relative body fat did not change with training, but VO2max increased an average of 18.5% (P < .05). LPLA, HTGLA, and LCAT activity were unaltered with exercise training. Except for a small but significant decrease in HDL-C (-5.5%) and an elevation in apoB (4.3%; P < .05 for both), the concentrations of serum lipids and apolipoproteins did not change over the training period. We conclude that in previously untrained women, menopausal status does not influence the exercise training response of serum lipids or apolipoproteins or activities of intravascular enzymes related to lipid transport.     

Phosphorylation and cytotoxicity of therapeutic nucleoside analogues: a comparison of alpha and gamma herpesvirus thymidine kinase suicide genes

The effect of a triphasic oral contraceptive containing ethinyl estradiol and gestodene (EE/GSD) on various lipid and lipoprotein parameters was compared with that of a monophasic formulation containing 35 micrograms ethinyl estradiol and 250 micrograms norgestimate (EE/NGM). Blood samples were collected from 46 women on days 2, 11, and 21 of the preceding control cycle and of the third, sixth, and twelfth treatment cycles. There was no significant difference between formulations with regard to the influence on any measured parameter. As compared with controls, a significant increase was observed in the plasma levels of total triglycerides (24-78%), total phospholipids (7-20%), very low density lipoprotein (VLDL) triglycerides (61-76%), VLDL-phospholipids (14-60%), low density lipoprotein (LDL) triglycerides (8-35%), LDL-phospholipids (28-30%), high density lipoprotein (HDL) cholesterol (8-16%), HDL 3-cholesterol (11-20%), HDL-triglycerides (17-66%), HDL-phospholipids, HDL 3-phospholipids (7-11%), apolipoprotein (apo) A-I (5-20%) and apo A-II (10-40%) during treatment with both formulations. In contrast, the LDL-cholesterol levels were significantly decreased. These changes in lipid metabolism appear to reflect a predominance of the effect of the estrogen component. The results indicate that both low dose oral contraceptives containing different progestins and different amounts of EE do not exert a deleterious effect on lipoprotein metabolism, as high HDL-cholesterol and low LDL-cholesterol levels are known as low risk factors of cardiovascular disease. In contrast to endogenous hypertriglyceridemia, an EE-induced rise in triglyceride levels does not appear to increase cardiovascular risk if LDL is not increased.     

Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL]. METHODS: After a 6-week dietary stabilization period, subjects entered a 4-week single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance during the the run-in were randomized into one of three parallel groups (placebo, 1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered in a triglyceride form contained in gelatin capsules. Primary outcome measurements were plasma phospholipid DHA content, serum triglycerides, high-density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C. RESULTS: The DHA content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose-dependent manner. Significant (p < 0.05) changes were observed in serum triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL-C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All lipid effects reached an apparent steady state within the first 3 weeks of treatment. CONCLUSION: Dietary DHA, in the absence of EPA, can affect lipoprotein cholesterol and triglyceride levels in patients with combined hyperlipidemia. The desirable triglyceride and HDL-C changes were present at a dose which did not significantly increased non-HDL-C or LDL-C. These preliminary findings suggest that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride form, may be an effective tool to aid in the management of hypertriglyceridemia.     

Serum lipoproteins in African Americans and whites with non-insulin-dependent diabetes in the US population

BACKGROUND: Despite the significant role that dyslipidemia is believed to play in the development of cardiovascular disease in diabetes, most studies examining diabetic dyslipidemia in the United States have not been population based, and very little data are available for African Americans with diabetes. We used data from a national survey to compare the effect of diabetes on lipid concentrations in African-American and white men and women. In addition, we examined other factors related to lipid concentrations and controlled for these factors in our analyses. METHODS AND RESULTS: The Second National Health and Nutrition Examination Survey included a representative sample of 4177 African Americans and whites in the US civilian noninstitutionalized population 20 to 74 years old. These persons were classified as having non-insulin-dependent diabetes mellitus (NIDDM) (n = 720) or as being nondiabetic (n = 3457) based on an oral glucose tolerance test and a medical history of diabetes. Subjects were given an interview and physical examination that included measurement of serum lipoproteins, body mass index, body fat distribution, dietary fat intake, alcohol consumption, frequency of smoking, and use of medications. By univariate analysis, a worse profile of mean cholesterol, triglycerides, and high-density lipoprotein cholesterol levels was generally apparent in NIDDM than in nondiabetic subjects, regardless of race or sex; a similar pattern was found for the prevalence of abnormal concentrations of these lipids. Lipid profiles appeared to be worse in whites with NIDDM than in African Americans. For mean total and low-density lipoprotein cholesterol, concentrations tended to be worse in women with NIDDM than in men. When other factors significantly affecting lipid levels were adjusted by multivariate analysis, we found that in all race/sex groups, total cholesterol was higher in NIDDM than in nondiabetic subjects but differences were not significant (P = 54), triglyceride concentrations were significantly higher in NIDDM subjects (P < .0001), and high-density lipoprotein cholesterol concentrations were lower in NIDDM subjects (P = .003). An interaction of diabetes with race was found for low-density lipoprotein cholesterol (P = .0001), where concentrations were substantially lower in NIDDM than in nondiabetic subjects among African Americans (P < .01) but slightly higher in NIDDM subjects among whites (P = .33). For other lipids, no differential effect of NIDDM was found by race or sex. CONCLUSIONS: In African-American and white men and women in the United States, NIDDM is associated with a pattern of dyslipidemia that may potentiate the atherosclerotic process. Diabetic treatment should include aggressive treatment of dyslipidemia to reduce this increased risk.     

Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum

OBJECTIVE: We tested the hypothesis that serum free (nonesterified) fatty acid and triglyceride concentrations are increased in nulliparous women with preeclampsia relative to women with uncomplicated pregnancies and that these lipids decrease post partum, consistent with the known resolution of clinical symptoms. The relationships between serum concentrations of these lipids and the lipid peroxidation metabolite malondialdehyde were also examined. STUDY DESIGN: Predelivery and 24 to 48 hour postpartum venous blood samples were collected from eight women with preeclampsia and nine women with uncomplicated pregnancies after an 8- to 10-hour fast. Sera were analyzed for concentrations of triglycerides, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and malondialdehyde. RESULTS: Antepartum serum triglyceride and free fatty acid concentrations were increased approximately twofold in women with preeclampsia relative to uncomplicated pregnancies (p <0.02 and 0.004, respectively). Total, high-density lipoprotein, and low-density lipoprotein cholesterol concentrations did not differ between groups. Concentrations of all lipids decreased significantly in both groups within 48 hours post partum. However, triglyceride and free fatty acid concentrations remained higher in women with preeclampsia (p<0.006, both variables). Triglyceride and free fatty acid concentrations correlated positively, both ante partum (R2 0.42, p<0.01) and post partum (R2 0.39, p<0.02). Antepartum concentrations of malondialdehyde were 50% higher in women with preeclampsia (p<0.01) and decreased post partum (p <0.02) but did not decrease in controls (p = 0.07). Antepartum serum triglycerides and free fatty acids correlated positively with malondialdehyde concentrations (R2 0.38, p <0.02, both cases). CONCLUSION: Triglycerides and free fatty acids, but not cholesterol, are increased in preeclampsia and correlate with the lipid peroxidation metabolite malondialdehyde. We speculate that these interactions may contribute to endothelial cell dysfunction in preeclampsia.     

Insulin resistance as an independent risk factor for carotid wall thickening

It has been reported that insulin resistance is associated with essential hypertension and that an aggregation of risk factors-hypertension, dyslipidemia, and glucose intolerance-together with insulin resistance leads to the more frequent appearance of coronary artery disease. We examined the relation between early asymptomatic atherosclerosis and these risk factors in 72 nondiabetic subjects with essential hypertension (41 men, 31 women) aged 50 to 59 years. Intima-media thickness and plaque formation of the carotid artery were assessed by B-mode ultrasonography, and insulin sensitivity was measured by the steady-state plasma glucose method. Lipoprotein profile was analyzed by ultracentrifugation. The intima-media thickness of the common carotid artery significantly correlated with systolic pressure; mean blood pressure; steady-state plasma glucose, indicating insulin resistance; fasting insulin; area under the curve of plasma insulin and glucose; body mass index; apolipoprotein B; apolipoprotein B in low-density lipoprotein; lower ratio of cholesterol to apolipoprotein B of low-density lipoprotein; and decreased high-density lipoprotein cholesterol. By multiple regression analysis, steady-state plasma glucose was the strongest risk, followed by lower high-density lipoprotein and systolic pressure. These three factors accounted for 54.9% of all the risk for increased intima-media thickness of the common carotid artery. In conclusion, insulin resistance was the strongest risk factor for carotid intima-media thickness, followed by lower high-density lipoprotein cholesterol and hypertension. An effort to maintain normal insulin sensitivity is essential for the prevention of early atheromatous lesions in essential hypertension.     

Relationship of alcohol consumption to changes in HDL-subfractions

Epidemiological studies have consistently shown an apparent protective effect of moderate alcohol consumption on coronary artery disease (CAD). This has been considered to be due to the rise in the high-density cholesterol lipoprotein (HDL-cholesterol). Since the response of the HDL-subfractions to moderate or heavy dose of alcohol is less clear, we now compared the high-density lipoprotein cholesterol status between groups consuming different amounts of alcohol. In this population-based survey serum total high-density lipoprotein cholesterol and its HDL2 and HDL3 subfractions were blindly compared between 264 consecutive middle-aged men (37 teetotallers, 137 moderate drinkers, 90 heavy drinkers) participating in a voluntary health screening and 104 male alcoholics. Alcohol consumption correlated significantly (P < 0.001) with total HDL-cholesterol, HDL2, HDL3 when all subjects (n = 368) were included but the correlation disappeared when alcoholics were excluded (n = 264). In comparison with teetotallers, alcoholics had significantly higher total HDL-cholesterol, HDL2 and HDL3 values (P < 0.001). Moderate or heavy intake of alcohol had no effect on HDL2 but increased the HDL3-fraction. If the protective effect of moderate alcohol consumption is mediated by high-density lipoprotein, it may not be accounted for by changes in the HDL2-fraction. The observed increases in the concentration of the HDL3-fraction, however, suggest that this subfraction may not be inert with respect to coronary disease and could possibly have a role in the protective effect.     

Cell surface binding and cellular internalization properties of suramin, a novel antineoplastic agent

BACKGROUND: A number of factors contribute to increased risk of coronary heart disease (CHD) among postmenopausal women, including atherogenic changes in serum cholesterol profiles, weight gain, and decreases in physical activity during the menopause. To date, no study has attempted to prevent elevations in primary CHD risk factors as women experience menopause. METHODS: A sample of 535 healthy premenopausal women, ages 44-50, were recruited for an ongoing 5-year randomized prevention trial testing whether increases in low-density lipoprotein cholesterol (LDL-C) and body weight can be prevented during the menopause with a dietary and behavioral intervention. The aim was to reduce total dietary and saturated fat and cholesterol, prevent weight gain, and increase physical activity levels. Changes in CHD risk factors after the first 6 months of treatment were analyzed comparing 253 intervention and 267 assessment-only control participants. RESULTS: The intervention group showed significant reductions in total cholesterol (-0.34 mmol/liter), LDL-C (-0.28 mmol/liter), triglycerides (-0.04 mmol/liter), weight (-4.8 kg), waist-hip ratio (-0.008), systolic blood pressure (-3.5 mm Hg), diastolic blood pressure (-2.2 mm Hg), serum glucose levels (-0.06 mmol/liter), and HDL-C (-0.06 mmol/liter) and significant increases in physical activity (+383 kcal). No significant changes were observed in the control group. CONCLUSION: Six-month results suggested that participants were receptive to the preventive approach to CHD risk reduction and were successful in making initial positive lifestyle changes. Follow-up data will evaluate long-term adherence to the intervention and the interaction between adherence and physiological changes during menopause.     

Regulation of eosinophil apoptosis: transduction of survival and death signals

To analyze the effects of supraphysiological dosages of growth hormone (GH) on carbohydrate (CH) and lipid metabolism, we investigated 87 girls with Turner syndrome (TS) in two studies: (1) a 4-year GH dose-response (DR) study comparing three groups with stepwise GH dosage increases up to 8 IU/m2/d in girls aged 2 to 11 years, and (2) a 2-year GH administration frequency-response (FR) study in girls aged 11 to 17 years, comparing once-daily (OD) and twice-daily (BID) injections of a total GH dose of 6 IU/m2/d in combination with low-dose ethinyl estradiol (50 ng/kg/d orally). At baseline, impaired glucose tolerance (IGT) was present in 6% of the girls, and at the end of the studies, in 5%. In the DR study, the area under the curve for time-concentration (AUCab) for glucose after an oral glucose tolerance test (OGTT) showed no change over time and no significant difference between any of the study groups. However, in all three DR groups, the AUCab for insulin, fasting glucose, the insulinogenic index, hemoglobin A1c (HbA1c), and urinary C-peptide (uCp) were all significantly higher after 4 years compared with pretreatment (P<.05). In the FR study, group differences were not observed. Compared with healthy Dutch control subjects, the median baseline levels in relatively young girls in the DR study were similar for total cholesterol (TC) and lower for high-density lipoprotein (HDL) cholesterol. In contrast, the median TC levels of relatively older girls in the FR study were higher and HDL levels were similar. With increasing GH dosage in the DR study, median TC and low-density lipoprotein (LDL) levels decreased, whereas median HDL levels increased. The changes after 4 years were significant, including a decrease in the atherogenic index. GH treatment at the supraphysiological dosages used in this study did not increase the frequency of IGT or clinical diabetes. However, we observed an increased insulinogenic index indicative of insulin resistance. Therefore, long-term follow-up study is warranted in these otherwise healthy subjects. OD injection regimens changed the lipid profile toward a more cardioprotective direction with a significant reduction of the TC/HDL cholesterol ratio.     

Type A factors as predictors of changes in the metabolic syndrome precursors in adolescents and young adults: A 3-year follow-up study.

The predictive associations of Type A factors with changes in some essential parameters of the cluster of disorders known as metabolic syndrome (Syndrome X) were studied during a 3-year follow-up period in 1,147 randomly selected healthy adolescents and young adults. Type A behavior was measured with the Hunter Wolf A-B Rating Scale. Physiological parameters studied were serum insulin, high-density and low-density lipoprotein cholesterol, triglycerides (TG), systolic and diastolic blood pressure, body-mass index (BMI), subscapular skinfold thickness (SSF), and centrality index. Among the Type A factors in boys and men, high baseline Aggression predicted an increase in the individual parameters of metabolic syndrome (i.e., insulin, TG, SSF, and BMI) as well as a global aggravation of the cluster of metabolic parameters. In girls and women, increases in Eagerness-Energy and Responsibility across the 3 years of follow-up predicted an increase in serum insulin and a decrease in SSF, respectively (PsycINFO Database Record (c) 2010 APA, all rights reserved)