Comparison of raloxifene and atorvastatin effects on serum lipids composition of healthy post-menopausal women

The aim of this study was to evaluate the effects of the selective oestrogen receptor modulator, raloxifene, and those of statin, atorvastatin, in reducing the cardiovascular risks associated with the post-menopausal status. A detailed study of serum lipid concentrations was performed in four groups of post-menopausal women receiving either placebo, raloxifene or atorvastatin alone or their combination for the period of three months.Group A (raloxifene) showed significant decrease in total cholesterol levels (P < 0.05) and an increase in phospholipids concentration (P < 0.05), followed by a marked reduction in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.01) and ApoB amounts (P < 0.001). Additionally, ApoA-I concentration was significantly increased (P < 0.01).Group B (atorvastatin) presented decreased cholesterol (P < 0.05) and triglycerides levels (P < 0.01), followed by elevated high-density lipoprotein cholesterol (HDL-C) concentration (P < 0.05) and low LDL-C amounts (P < 0.001). ApoA-I was significantly increased (P < 0.001) whereas ApoB was reduced (P < 0.001).The combined treatment in Group C (raloxifene and atorvastatin) showed significant changes in the majority of serum lipids. In particular, total cholesterol was reduced (P < 0.001), as well as triglycerides (P < 0.001) levels. Phospholipids were raised (P < 0.01) whereas LDL-C was reduced (P < 0.001) as was ApoB (P < 0.001). Furthermore, ApoA-I was elevated (P < 0.001). A further attempt to evaluate each treatment group was performed and the significance of these results is discussed. (Mol Cell Biochem 261: 71–75, 2004)     

Determining oxidant and antioxidant status in patients with genital warts

Abstract

Objectives

Warts are abnormal skin growths caused by human papilloma virus (HPV) infections within the skin of patients. Genital warts usually appear in the perianal and perigenital regions. Asymptomatic warts may be activated after years and may damage natural immunity. The inflammation that occurs during this process may lead to an imbalance between the prooxidant and the antioxidant systems. The aim of this study was to investigate erythrocyte glutathione peroxidase (GSH-Px) activity, serum paraoxonase enzyme levels, and oxidative stress levels in patients with genital warts.

Patients and Methods

In total, 32 patients with genital warts and 35 healthy subjects were included in this study. Erythrocyte GSH-Px activity, serum catalase activity, and paraoxonase enzyme, and malondialdehyde (MDA) levels were determined.

Results

Erythrocyte GSH-Px activity, serum MDA levels, and catalase activity were significantly higher in patients with genital warts than in controls (P < 0.01, P < 0.05, and P < 0.05, respectively). However, serum paraoxonase enzyme levels were not significantly different between groups (P > 0.05). Serum triglyceride levels were significantly lower in patients with genital warts than in controls (P < 0.01). However, there were no statistically signi?cant differences between groups with respect to total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol levels (all P > 0.05).

Conclusions

Our data suggest that oxidative stress is increased in genital warts. Increased oxidative stress levels may contribute to the pathogenesis of genital warts, and prolonged HPV infection due to chronic inflammation could also affect oxidative stress.     

Influence of Dietary Copper Methionine Concentrations on Growth Performance,Digestibility of Nutrients,Serum Lipid Profiles,and Immune Defenses in Broilers

A 42-day experiment was conducted to evaluate the influence of dietary copper (Cu) concentrations on growth performance, nutrient digestibility, and serum parameters in broilers aged from 1 to 42 days. Five hundred forty 1-day-old broilers were randomly assigned into 1 of the following 6 dietary treatments: (1) control (basal diet without supplemental Cu), (2) 15 mg/kg supplemental Cu (Cu15), (3) 30 mg/kg supplemental Cu (Cu30), (4) 60 mg/kg supplemental Cu (Cu60), (5) 120 mg/kg supplemental Cu (Cu120), and (6) 240 mg/kg supplemental Cu (Cu240), Cu as copper methionine. A 4-day metabolism trial was conducted during the last week of the experiment feeding. The results showed that dietary Cu supplementation increased the average daily gain and the average daily feed intake (P < 0.01). The feed gain ratio, however, was not affected by dietary Cu (P > 0.10). Additionally, dietary Cu supplementation increased the digestibility of fat and energy (P < 0.05). The concentration of serum cholesterol, triglycerides, and high-density lipoprotein cholesterol decreased with dietary Cu supplementation (P < 0.05). The activities of serum Cu-Zn superoxide dismutase (P < 0.05), glutathione peroxidase (P < 0.05), and ceruloplasmin (P = 0.09), on the contrary, were increased by Cu addition. For immune indexes, dietary Cu supplementation increased serum IgA and IgM (P < 0.05). In addition, the activities of serum ALT increased with increasing dietary Cu supplementation (P < 0.05). In conclusion, our data suggest that Cu supplementation can increase fat digestibility and promote growth. Additionally, dietary Cu supplementation can reduce serum cholesterol and enhance antioxidant capacity in broilers.

     

Acquired liver fat is a key determinant of serum lipid alterations in healthy monozygotic twins

Objective: The effects of acquired obesity on lipid profile and lipoprotein composition in rare BMI‐discordant monozygotic (MZ) twin pairs were studied. Design and Methods: Abdominal fat distribution, liver fat (magnetic resonance imaging and spectroscopy), fasting serum lipid profile (ultracentrifugation, gradient gel‐electrophoresis, and colorimetric enzymatic methods), and lifestyle factors (questionnaires and diaries) were assessed in 15 BMI‐discordant (within‐pair difference [Δ] in BMI >3 kg/m²) and nin concordant (ΔBMI <3 kg/m²) MZ twin pairs, identified from two nationwide cohorts of Finnish twins. Results: Despite a strong similarity of MZ twins in lipid parameters (intra‐class correlations 0.42‐0.90, P < 0.05), concentrations of apolipoprotein B (ApoB), intermediate‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein 3a% (HDL3a%), and HDL3c% were higher (P < 0.05) and those of HDL cholesterol, HDL2‐C, and HDL2b% were lower (P < 0.01) in the heavier co‐twins of BMI‐discordant pairs. The composition of lipoprotein particles was similar in the co‐twins. When BMI‐discordant pairs were further divided into liver fat‐discordant and concordant (based on median for Δliver fat, 2.6%), the adverse lipid profile was only seen in those heavy co‐twins who also had high liver fat. Conversely, BMI‐discordant pairs concordant for liver fat did not differ significantly in lipid parameters. In multivariate analyses controlling for Δsubcutaneous, Δintra‐abdominal fat, sex, Δsmoking and Δphysical activity, Δliver fat was the only independent variable explaining the variation in ΔApoB, Δtotal cholesterol, and ΔLDL‐C concentration. Conclusions: Several pro‐atherogenic changes in the amounts of lipids but not in the composition of lipoprotein particles were observed in acquired obesity. In particular, accumulation of liver fat was associated with lipid disturbances, independent of genetic effects.     

Effects of Apigenin on the Expression of LOX-1, Bcl-2, and Bax in Hyperlipidemia Rats

We aimed to investigate the impact of apigenin on LOX-1, Bcl-2, and Bax expression in hyperlipidemia rats and explore the possible molecular pathological mechanism of apigenin in improving hyperlipidemia and preventing atherosclerosis. In hyperlipidemia models, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and the LOX-1 protein expression were apparently increased (P<0.01), while the high-density lipoprotein cholesterol (HDL-c) levels and the ratio of Bcl-2/Bax were reduced significantly (P<0.01) in comparison with the standard control group. After the treatment of apigenin, the levels of TC, TG, LDL-c, and the LOX-1 protein expression were noticeably decreased (P<0.01), while the levels of HDL-c and the Bcl-2/Bax ratio were increased (P<0.01). The intima was thickened and had protrusions in the hyperlipidemia model group compared to the normal control group. In comparison with the atherosclerosis model group, the degree of aortic lesions in the low-dose, middle-dose, high-dose groups was alleviated. Apigenin can reduce the level of blood lipid, improve hyperlipidemia, and prevent atherosclerosis in hyperlipidemia rats. The molecular mechanism may be related to inhibiting LOX-1 gene expression and increasing the Bcl-2/Bax ratio.     

Association of plasma brain-derived neurotrophic factor and cardiovascular risk factors and prognosis in angina pectoris

Background

Collateral circulation can protect and preserve the myocardium against episodes of ischemia and reduce cardiovascular events. Brain-derived neurotrophic factor (BDNF) is an angiogenic regulator promoting angiogenesis. We compared the association of plasma levels of BDNF and C-reactive protein, an established marker, and risk factors of cardiovascular dysfunction and prognosis in patients with angina pectoris.

Methods

We enrolled 885 patients with angina pectoris. Plasma BDNF and CRP were measured by ELISA. Patients were prospectively followed for a median of 48 months (interquartile range 37–59 months), and information on further coronary events and mortality was collected.

Results

Multiple risk factors for cardiovascular disease were independent determinants of low plasma BDNF level in patients with angina pectoris. Plasma BDNF was inversely associated with levels of triglycerides and low-density lipoprotein cholesterol, presence of diabetes mellitus, fibrinogen level, male sex and age and positively with high-density lipoprotein cholesterol level and platelet count. During follow-up, 15.2% of patients experienced a major coronary event (MCE), and 10.5% died. The plasma BDNF level was an independent predictor of 4-year MCE (adjusted hazard ratio = 1.25 with 95% confidence interval 1.10–1.41, P < 0.01 for each unit increase in the natural logarithm of the BDNF level) and of 4-year mortality (adjusted hazard ratio = 1.29, 95% confidence interval 1.11–1.47, P < 0.01).

Conclusion

Multiple cardiovascular risk factors are associated with plasma BDNF level in patients with angina pectoris, and low plasma BDNF may be associated with future coronary events and mortality in these patients.     

Epipolymorphisms within lipoprotein genes contribute independently to plasma lipid levels in familial hypercholesterolemia

Gene polymorphisms associated so far with plasma lipid concentrations explain only a fraction of their heritability, which can reach up to 60%. Recent studies suggest that epigenetic modifications (DNA methylation) could contribute to explain part of this missing heritability. We therefore assessed whether the DNA methylation of key lipoprotein metabolism genes is associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels in patients with familial hypercholesterolemia (FH). Untreated FH patients (61 men and 37 women) were recruited for the measurement of blood DNA methylation levels at the ABCG1, LIPC, PLTP and SCARB1 gene loci using bisulfite pyrosequencing. ABCG1, LIPC and PLTP DNA methylation was significantly associated with HDL-C, LDL-C and triglyceride levels in a sex-specific manner (all P < 0.05). FH subjects with previous history of coronary artery disease (CAD) had higher LIPC DNA methylation levels compared with FH subjects without CAD (P = 0.02). Sex-specific multivariable linear regression models showed that new and previously reported epipolymorphisms (ABCG1-CpGC3, LIPC-CpGA2, mean PLTP-CpGC, LPL-CpGA3, CETP-CpGA2, and CETP-CpGB2) significantly contribute to variations in plasma lipid levels (all P < 0.001 in men and P < 0.02 in women), independently of traditional predictors such as age, waist circumference, blood pressure, fasting plasma lipids and glucose levels. These results suggest that epigenetic perturbations of key lipoprotein metabolism genes are associated with plasma lipid levels, contribute to the interindividual variability and might partially explain the missing heritability of plasma lipid levels, at least in FH.     

Carbohydrate restriction and dietary cholesterol distinctly affect plasma lipids and lipoprotein subfractions in adult guinea pigs

To evaluate the effects of carbohydrate restriction (CR) and dietary cholesterol on lipoprotein metabolism, adult male guinea pigs (10 guinea pigs/diet) were fed either low (0.04 g/100 g) or high (0.25 g/100 g) amounts of dietary cholesterol, in combination with either low (10% total energy) or high (54.2% total energy) dietary carbohydrate (control groups) for a total of four groups: high carbohydrate–low cholesterol (control-L), high carbohydrate–high cholesterol (control-H), low carbohydrate–low cholesterol (CR-L) and low carbohydrate–high cholesterol (CR-H). Plasma triglyceride concentrations were lower (P<.01%), while high-density lipoprotein cholesterol concentrations were higher (P<.05) in the CR groups compared to the control groups. In contrast, high dietary cholesterol (CR-H and control-H) resulted in higher concentrations of total and low-density lipoprotein (LDL) cholesterol compared to those guinea pigs fed the low-cholesterol diets (P<.01). Dietary cholesterol significantly increased the total number of LDL particles (P<.001) and the number of small LDL (P<.001), as determined by nuclear magnetic resonance. In contrast, carbohydrate restriction (CR-L and CR-H) resulted in lower concentrations of medium very-low-density lipoprotein and small LDL particles compared to the high-carbohydrate groups. Plasma lecithin:cholesterol acyltransferase (LCAT) activity was decreased and cholesterol ester transfer protein activity was increased by dietary cholesterol, whereas carbohydrate restriction increased LCAT activity (P<.05). These findings are similar to those observed in humans, thus validating the use of adult guinea pigs to study lipid responses to carbohydrate restriction. The results also indicate that the atherogenicity of lipoproteins induced by high dietary cholesterol is attenuated by carbohydrate restriction in guinea pigs.     

Effects of <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis> MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet

The objective of this study was to evaluate the effects of Lactobacillus plantarum MA2, an isolate from Chinese traditional Tibet kefir, on cholesterol-lowering and microflora of rat in vivo. Rats were fed on cholesterol-enriched experimental diet, supplemented with lyophilized L. plantarum MA2 powder, with a dose of 10¹¹ cells/day per mice. The results showed that L. plantarum MA2 feeding significantly lowered serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides level, while there was no change in high-density lipoprotein cholesterol. In addition, liver total cholesterol and triglycerides was also decreased. However, fecal cholesterol and triglycerides was increased significantly (P < 0.05) in comparison with the control. Also, L. plantarum MA2 increased the population of lactic acid bacteria and bifidobacteria in the fecal, but it did not change the number of Escherichia coli as compared to control. Moreover, pH, moisture, and organic acids in the fecal were also measured. The present results indicate the probiotic potential of the L. plantarum MA2 strain in hypocholesterolemic effect and also increasing the probiotic count in the intestine.     

Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet

We previously reported that carbohydrate restriction (CR) (10–15% en) during a weight loss intervention lowered plasma triglycerides (TG) by 45% in male subjects (P<.001). However, those subjects with a higher intake of cholesterol provided by eggs (640 mg additional cholesterol, EGG group) had higher concentrations of high-density lipoprotein (HDL) cholesterol (P<.0001) than the individuals consuming lower amounts (0 mg of additional cholesterol, SUB group). The objectives of the present study were to evaluate whether CR and egg intake (1) modulate circulating carotenoids and (2) affect the concentrations of plasma apolipoproteins (apo), lipoprotein size and subfraction distribution. CR decreased the number of large and medium very low-density lipoprotein cholesterol subclasses (P<.001), while small low-density lipoprotein (LDL) were reduced (P<.001). In agreement with these observations, a decrease in apo B (P<.01) was observed. In addition, CR resulted in a 133% increase in apo C-II and a 65% decrease in apo C-III (P<.0001). Although an increase of the larger LDL subclass was observed for all subjects, the EGG group had a greater increase (P<.05). The EGG group also presented a higher number of large HDL particles (P<.01) compared to the SUB group. Regarding carotenoids, CR resulted in no changes in dietary or plasma α- or β-carotene and β-cryptoxanthin, while there was a significant reduction in both dietary and plasma lycopene (P<.001). In contrast, dietary lutein and zeaxanthin were increased during the intervention (P<.05). However, only those subjects from the EGG group presented higher concentrations of these two carotenoids in plasma, which were correlated with the higher concentrations of large LDL observed in the EGG group. These results indicate that CR favorably alters VLDL metabolism and apolipoprotein concentrations, while the components of the egg yolk favor the formation of larger LDL and HDL leading to an increase in plasma lutein and zeaxanthin.