Cytochrome P-450scc activity and substrate supply in human placental trophoblasts.The degree of saturation of cytochrome P-450scc with cholesterol and the substrate turnover number of the cytochrome in cultured trophoblasts and mitochondria from the human placenta were investigated. Cholesterol sulfate was found to be a suitable substrate for probing the degree of saturation of cytochrome P-450scc with substrate during culture and in isolated mitochondria, since it enabled the maximum velocity of the cholesterol side-chain cleavage reaction to be estimated. In contrast, 25-hydroxycholesterol and low density lipoprotein supported trophoblast progesterone production at lower rates than that measured with saturating cholesterol sulfate. In the absence of exogenous substrate, the highest rate of progesterone synthesis by trophoblasts was observed at the beginning of the culture. With cholesterol sulfate as substrate, the turnover number of cytochrome P-450scc in cultured cells was 2.8 min-1 and was not significantly different to the turnover number of the cytochrome for placental mitochondria, where cholesterol is known to be saturating. Results indicate that cholesterol is limiting for progesterone synthesis in cultured trophoblasts even in the presence of lipoprotein rich medium and 8-bromo-cAMP. The concentration of cytochrome P-450scc in trophoblasts was only 20% of that measured for placental homogenate suggesting an induction of the cytochrome occurs when the trophoblasts fuse in vivo to form syncytiotrophoblasts.

Increased high-density lipoprotein cholesterol concentration in alcoholics is related to low cholesteryl ester transfer protein activity.Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins. Since alcoholics have high HDL cholesterol and low LDL cholesterol levels, a defect in cholesteryl ester transfer could be responsible for the alcohol-induced alteration in cholesterol distribution between lipoproteins. To test this hypothesis, we compared CETP activity in plasma from 30 alcoholics without severe liver damage and 16 control subjects. Plasma CETP activity was 28% lower in the alcoholics compared with the controls (P less than 0.001), while the teetotallers among the latter had slightly higher CETP activity than those who consumed alcohol in moderation. CETP activity increased slowly after ethanol withdrawal, but did not reach the control level within the 7-day observation period. A positive correlation was observed between plasma CETP activity and the LDL cholesterol HDL cholesterol ratio (r = 0.480, P less than 0.002), whereas CETP activity showed a negative correlation with HDL cholesterol level (r = -0.467, P less than 0.001). The results indicate that defective transfer of cholesteryl esters from HDL to LDL contributes to the high HDL cholesterol levels in alcoholics.

Apolipoprotein E polymorphism in middle-aged Belgian men: phenotype distribution and relation to serum lipids and lipoproteins.Apo E phenotype was determined in 760 Belgian men, aged 35 to 59 years. Serum lipids and lipoproteins were related to the apo E polymorphism in 734 participants. By comparison with the most frequent apo E3/3 phenotype, the presence of the epsilon2 allele was associated with a lower serum total and non-HDL cholesterol, and with a lower apo B and a higher HDL cholesterol, independently of age, lifestyle factors and apo E concentration. In contrast, the presence of the epsilon4 allele was associated with a higher serum total and non-HDL cholesterol, and with a lower HDL cholesterol and a lower apo AI. The apo E phenotype explained 17.4% of the variance in apo E concentration; the proportion of the variance in total cholesterol, HDL cholesterol, apo AI and apo B levels explained by the apo E polymorphism was low but statistically significant. Among the lifestyle factors, waist to hip ratio was the only variable significantly associated with apo E concentration. The data suggest that besides the well-documented increasing effect on non-HDL cholesterol, the epsilon4 allele could further predispose to Coronary Heart Disease through a decreasing effect on HDL while the epsilon2 allele could exert a protective influence through both a decreasing effect on non-HDL cholesterol and an increasing effect on HDL cholesterol.

Should we be measuring blood cholesterol levels in young adults?Should we measure blood cholesterol levels in all adults, or only in those at high risk of Coronary Heart Disease (CHD)? Most men under the age of 35 years and women under the age of 45 years--roughly half the adult population--are at very low short-term risk of CHD. One consequence is that drug treatment to lower high blood cholesterol levels in the average young adult is an extremely expensive means of prolonging life; the estimated $1 million to $10 million per year of life is 100 to 1000 times the cost of other approaches. Individualized dietary treatment is somewhat cheaper but relatively ineffective. Another consequence of the low CHD risk in young adults is the greater likelihood that intervention may have harmful effects that outweight the benefits. Meta-analysis of primary prevention trials in middle-aged men reveal an increase in non-CHD deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths. This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death. We conclude that the policy of screening and treating high blood cholesterol levels in young adults is neither cost-effective, nor does it satisfy ethical standards requiring strong evidence that preventive interventions do more good than harm. Fortunately, cholesterol screening in young adults is also not necessary: most CHD events associated with high blood cholesterol levels in this population will not occur for decades and can be prevented by treatment that is begun in middle age. Cholesterol screening and treatment in young adults should be limited to individuals with known coronary disease or other unusual factors that place them at high short-term risk of CHD death.

Serum cholesterol and leptin levels in patients with borderline personality disorder.The association between low or lowered cholesterol and impulsivity, aggressive behaviours and suicide remains controversial. In the present study, cholesterol and leptin levels of patients with borderline personality disorder in whom impulsivity, aggressive behaviours and suicide attempts are clearly established have been compared with those of healthy controls. The study group consisted of 16 patients with borderline personality disorder and 16 healthy controls. All patients were assessed with the Barratt Impulsivity Scale (BIS), Buss-Durkee Hostility Inventory (BDHI) and Hamilton Depression Rating Scale (HDRS). Fasting serum cholesterol and leptin levels were measured. The mean cholesterol and leptin levels of the patient group were significantly lower than those of the controls. Likewise, the patients with current suicidal thoughts and a history of suicide attempt had statistically significantly lower cholesterol and leptin levels compared with the patients without those features. There was an inverse correlation between both cholesterol and leptin levels, and impulsivity as determined by the BIS or aggression as determined by the BDHI, but no correlation between both cholesterol and leptin levels and the HDRS was found in the patients. In conclusion, the present study demonstrates that the patients with borderline personality disorder have lower cholesterol and leptin levels than healthy controls. Low serum cholesterol and leptin levels are associated with all dimensions of the disorder - impulsivity, aggression and suicidality - but are not associated with the presence and the severity of comorbid depression.

Short- and long-term association of serum cholesterol with mortality. The 25-year follow-up of the Finnish cohorts of the seven countries study.The association of serum cholesterol with cause-specific and all-cause mortality was assessed in a cohort of 1,426 men aged 40-59 years who were free of clinically evident heart disease at baseline (1959). A total of 748 deaths (53 percent of the participants) occurred during the 25-year follow-up period. Men with high serum cholesterol levels at baseline had high mortality due to Coronary Heart Disease during both the early and later parts of the follow-up period. In contrast, the association of serum cholesterol with mortality due to causes other than Coronary Heart Disease changed during follow-up (interaction of cholesterol with follow-up period: p = 0.004). During the first 10 years of follow-up, despite their high coronary mortality, men with high cholesterol levels had lower all-cause mortality (age-adjusted relative risk = 0.71 for serum cholesterol above 5.79 mmol/liter vs. below 5.80 mmol/liter; p = 0.03) because of their low cancer mortality (relative risk = 0.55, p = 0.03) and residual mortality (relative risk = 0.49, p less than 0.01). During the last 15 years of follow-up, cholesterol at baseline was no longer associated with mortality due to causes other than Coronary Heart Disease, and consequently, because of their high coronary mortality, men with high cholesterol levels also had higher all-cause mortality (relative risk = 1.22, p = 0.05). The results suggest that to fully analyze the association of serum cholesterol with all-cause mortality, the follow-up period should be sufficiently long--possibly more than 10 years--and the possibility of a change in the direction of the association studied should always be considered.

Do elevated levels of abdominal visceral adipose tissue contribute to age-related differences in plasma lipoprotein concentrations in men?Age-related differences in body fat and more specifically in the accumulation of abdominal visceral adipose tissue were examined as a potential covariate for the alteration in the plasma lipoprotein profile found with aging. For that purpose, results from 79 young adults (aged 24.5 +/- 4.0 years) were compared to 61 middle-aged men (54.7 +/- 6.4 years). Younger men had significantly lower body fat mass and abdominal visceral adipose tissue area measured by computed tomography than middle-aged men (P < 0.0001). Plasma cholesterol, triglyceride, apolipoprotein (apo) B, low density lipoprotein (LDL)-cholesterol and LDL apo B levels, as well as the ratio of plasma cholesterol to high density lipoprotein (HDL)-cholesterol were all significantly lower in younger men as compared to middle-aged men (P < 0.0001). The comparison of younger men to middle-aged men with comparable levels of abdominal visceral fat and total body fat eliminated the age-related differences in plasma triglyceride and in the ratio of plasma cholesterol to HDL-cholesterol, whereas the difference in plasma apolipoprotein B levels, although still significant, was largely reduced. Age-related differences in plasma cholesterol and in LDL-cholesterol levels were still observed after this matching procedure and the differences between age-groups were essentially of similar magnitude than before pairing. In summary, these results suggest that the deterioration of plasma lipoprotein profile observed in middle-aged men as compared to young adult men is partly mediated by concomitant increases in total body fat and abdominal visceral adipose tissue. However, other factors related to the aging process appear to be involved, particularly for the age-related increase in plasma LDL-cholesterol.

Quercetin dihydrate and gallate supplements lower plasma and hepatic lipids and change activities of hepatic antioxidant enzymes in high cholesterol-fed rats.This study was designed to test the lipid-lowering and antioxidant activity of two bioflavonoids, quercetin dihydrate and gallate. Four groups of rats were given a semisynthetic diet containing 10 g cholesterol/kg for six weeks. The control group received only a high-cholesterol diet, whereas the other three groups received a diet including 1 g lovastatin, 1 g quercetin dihydrate, or 1 g gallate/kg. The quercetin dihydrate and gallate supplements both significantly lowered the plasma lipid and hepatic cholesterol levels compared to those of the control. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was significantly lowered by the quercetin dihydrate when compared to the other groups, while the hepatic acyl CoA: cholesterol acyltransferase (ACAT) activity was only significantly higher in the control group. The overall potential for antioxidant protection was significantly enhanced by the quercetin dihydrate and gallate supplements through lowering the plasma and hepatic thiobarbituric acid reactive substances (TBARS) levels and increasing the hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in high-cholesterol-fed rats. These results suggest that the supplementation of quercetin dihydrate and gallate promotes an increase in fecal sterols, which in turn leads to a decreased absorption of dietary cholesterol as well as lower plasma and hepatic cholesterol.

Plasma lipids and lipoproteins during first trimester in pregnant Nigerian women: Ilorin experience.Thirty-two pregnant women in their first trimester with a mean age of 29.5 years, 32 age matched non-pregnant controls were included in this study. They were bled after 14-hour fasting. This study was between October 2000 and October 2001. Plasma total cholesterol, triglyceride and HDL- cholesterol were assayed. LDL-cholesterol was obtained through Frieldwald formula average as mean were calculated using Epi info version 6.0 and level of significant difference decided at p<0. 05. The mean age of the subjects was 9.5 years. Compared to the concentration in non-pregnant women [controls] the plasma level of total cholesterol and HDL-cholesterol were found to be significantly lower p<0.05. However the levels of plasma triglyceride and LDL-cholesterol were found to be significantly higher in the pregnant women than the control group [p<0.05]. This study revealed that the level of total plasma cholesterol is low in middle part of first trimester. We therefore suggest that in interpreting the result of total cholesterol in first trimester the gestation age should be put into consideration.

A longitudinal evaluation of oxidative stress in trauma patients.BACKGROUND: The purpose of this study was to determine the course of oxidative stress in trauma patients as measured by antioxidant disappearance and modulation of DNA damage. The study also explored the role of injury severity and the effect of changes in plasma lipoprotein concentration as the result of hemodilution on lipid-soluble plasma antioxidant concentrations. METHODS: The study population included 17 adult male trauma patients in an urban level-1 trauma hospital and 12 healthy adult male controls. Blood was collected immediately after admission in the emergency room, and on days 2, 3, 4, 6, and 8 of admission. Plasma antioxidant concentrations and total cholesterol concentrations were evaluated. DNA damage was evaluated using the ratio of 8-hydroxydeoxyguanosine to deoxyguanosine (8OhdG to dG). Admission data were compared with data from controls. RESULTS: Plasma antioxidant concentrations (except alpha-tocopherol) significantly decreased by 9.9% to 34.3% in the 24 hours after trauma and remained depressed throughout day 8. Repeated measures regression analysis for trend showed a significant increase in unadjusted alpha-tocopherol from day 1 to day 8 (p < .008). No other unadjusted antioxidant or plasma cholesterol showed a significant change. After individually adjusting antioxidant concentrations by total cholesterol, only gamma-tocopherol (22.2%) and lycopene (22.6%) were decreased (p < .04) in the 24 hours after trauma. Repeated measures regression analysis for trend for the cholesterol-adjusted antioxidants showed a significant decrease from day 1 to day 8 for cholesterol-adjusted alpha-carotene (p < .007) and beta-carotene (p < .007). Trauma patients were divided into more and less severely injured groups based on Injury Severity Score (ISS). Decreases in antioxidant concentration from day 1 to day 2 were found for the patients in the more injured group, with no significant differences from day 1 to day 2 in the less severely injured group. Cholesterol-adjusted gamma-to copherol (29.7%, p < .003) and lycopene (32.7%, p < .05) decreased from day 1 to day 2 in the more severely injured group. Using repeated measures regression analysis for trend, the only antioxidant that was significantly different in the high versus low ISS groups from day 1 through day 6 was cholesterol-adjusted lutein-zeaxanthin (p < .02). Compared with controls, trauma patients had significantly lower (27.3% to 64.9%) concentrations of all cholesterol-adjusted antioxidants at day 1 except for lycopene. Trauma patients had higher leukocyte 8OhdG to dG ratios at admission (42.6%, p < .05), but 8OhdG to dG ratios tended to decrease over the 24 hours after trauma (p < .07). This decrease was greater in the 3 trauma patients with an admission 8OhdG to dG ratio greater than 6 x 10(-5) (59.3% versus 0.05%, p < .03). CONCLUSIONS: The difference in antioxidant concentrations between trauma patients and controls may have been associated with oxidative stress or with a poorer diet. The difference between antioxidant concentrations and cholesterol-adjusted antioxidant concentrations is likely caused by hemodilution or by changes in plasma lipid levels as a result of trauma. Therefore, individually adjusting lipid-soluble antioxidant concentrations by total cholesterol concentrations is important in trauma patients. Leukocyte 8OhdG to dG ratios were already elevated in trauma patients on admission but returned nearly to control levels 24 hours later, indicating short-term responsiveness to DNA oxidation in trauma patients and an extensive capacity for DNA repair within 24 hours.