Carl W. Lawton

Dietary effects on cardiovascular disease risk factors : Beyond saturated fatty acids and cholesterol

Hypercholesterolemia represents a significant risk for cardiovascular disease (CVD). While diet intervention remains the initial choice for the prevention and treatment of CVD, the nature of the dietary modification remains controversial. For example, reducing calories from total fat, without decreasing saturated fat intake results in insignificant changes in low density lipoprotein cholesterol (LDL-C). Similarly, diet interventions that focus solely on lowering dietary cholesterol and saturated fat intake not only decrease LDL-C, but also high density lipoprotein cholesterol (HDL-C) and therefore may not improve the lipoprotein profile. This brief review summarizes dietary interventions that lower LDL-C without affecting HDL-C levels. These interventions include soy protein, soluble fiber, soy lecithin and plant sterols. This review also includes some of the reported dietary interventions, such as polyphenols, isoflavones, folic acid and vitamins B6 and B12, which reduce the risk of CVD without changes in lipoprotein cholesterol.

Comparative cholesterol lowering properties of vegetable oils: beyond fatty acids.

Objective: Our laboratory has previously reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Although RBO has up to three times more serum cholesterol-raising saturated fatty acids (SATS) than some unsaturated vegetable oils, we hypothesized that its greater content of the unsaponifiables would compensate for its high SATS and yield comparable cholesterol-lowering properties to other vegetable oils with less SATS. Methods: To study the comparative effects of different unsaturated vegetable oils on serum lipoprotein levels, nine cynomologus monkeys (Macaca fascicularis) were fed diets, for four weeks, in a Latin square design, containing rice bran, canola or corn oils (as 20% of energy) in a basal mixture of other fats to yield a final dietary fat concentration of 30% of energy. All animals were fed a baseline diet containing 36% of energy as fat with 15% SATS, 15% monounsaturated fatty acids (MONOS) and 6% polyunsaturated fatty acids (POLYS). Results: Despite the lower SATS and higher MONOS content of canola oil and the higher POLYS content of corn oil, RBO produced similar reductions in serum total cholesterol (TC) (−25%) and low density lipoprotein cholesterol (LDL-C) (−30%). In addition, as compared to the baseline diet, the reduction in serum TC and LDL-C cholesterol with RBO was not accompanied by reductions in high density lipoprotein cholesterol (HDL-C) which occurred with the other two dietary oils. Using predictive equations developed from data gathered from several studies with non-human primates, we noted that the observed serum TC and LDL-C lowering capabilities of the RBO diet were in excess of those predicted based on the fatty acid composition of RBO. Conclusions: These studies suggest that non-fatty acid components (unsaponifiables) of RBO can contribute significantly to its cholesterol-lowering capability.

Gender differences in response to a hypercholesterolemic diet in hamsters: effects on plasma lipoprotein cholesterol concentrations and early aortic atherosclerosis

Gender is a strong predictor of coronary heart disease (CHD) susceptibility and reports indicate that males are more likely to develop CHD compared to age-matched premenopausal females. To test whether similar gender differences exist in hamsters, 16 male and 16 female F1B Golden Syrian hamsters, aged 10 weeks, were fed a hypercholesterolemic nonpurified diet (HCD) containing 10% coconut oil and 0.05% cholesterol for 12 weeks. Plasma lipid and lipoprotein cholesterol concentrations, LDL oxidative susceptibility, LDL tocopherol concentrations, LDL fatty acid composition, LDL particle size, plasma estradiol and testosterone concentrations, and early aortic atherosclerosis were analyzed. Female hamsters had significantly lower plasma total cholesterol and nonhigh-density lipoprotein cholesterol (nonHDL-C) and greater high-density lipoprotein cholesterol (HDL-C) concentrations compared to male hamsters (-15, -33, and 33%; respectively). Female hamsters had significantly greater LDL particle size (4%), LDL 22:6 (21%) fatty acid, and rate of LDL oxidation (34%) compared to male hamsters. Female hamsters had a significantly higher concentration of plasma estradiol (49%) compared to male hamsters. Female hamsters also had significantly less early aortic atherosclerosis compared to male hamsters (-77%). In female hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r = 0.76, P<0.0007), LDL particle size (r = -0.66, P<0.005), plasma TC (r = 0.68. P<0.004), and lag phase of LDL oxidation (r = 0.84. P<0.02). In male hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r = 0.52, P<0.04), plasma TC (r = 0.55, P<0.03), plasma TG (r = 0.79, P<0.0003), and LDL 22:6 (r = -0.78, P<0.03) with no association with any measures of LDL oxidation susceptibility. This study demonstrates that female hamsters have an improved plasma lipoprotein cholesterol profile, larger LDL particle size, and less early aortic atherosclerosis compared to male hamsters fed the same HCD.

The greater atherogenicity of nonpurified diets versus semipurified diets in hamsters is mediated via differences in plasma lipoprotein cholesterol distribution, ldl oxidative susceptibility, and plasma α-tocopherol concentration

In the current study, plasma lipid, lipoprotein cholesterol and α-tocopherol concentrations, LDL oxidative susceptibility, and early aortic atherosclerotic responses of feeding a hypercholesterolemic nonpurified or semipurified diet containing similar levels of macro- and certain micro-nutrients were compared in hamsters. Although plasma total cholesterol (TC) concentrations in the hamsters fed the semipurified versus nonpurified diet were significantly higher (P < 0.05), non-high density lipoprotein cholesterol (non-HDL-C) concentrations were 41% greater in hamsters fed the non-purified diet (P < 0.05). This greater plasma non-HDL-C concentration, coupled with significantly lower plasma concentrations of high-density lipoprotein cholesterol (HDL-C) (P < 0.05), resulted in a greater plasma non-HDL-C/HDL-C and TC/HDL-C ratios for the nonpurified versus the semipurified diet (P < 0.05). Despite comparable amounts of dietary vitamin E, plasma α-tocopherol concentrations were 233% higher in the semipurified versus nonpurified diet (P < 0.05). Resistance of LDL to oxidation, as measured by lag phase of conjugated diene formation, was reduced nearly 50%, and the rate of formation of conjugated dienes was 105% higher in the nonpurified versus the semipurified diet, respectively (P < 0.05). Early aortic atherosclerosis was fivefold greater in hamsters fed the nonpurified versus semipurified diet. These results suggest that, despite similar dietary concentrations of many of the macro- and micro-nutrients, ingestion of hypercholesterolemic nonpurified diets by hamsters is associated with a more atherogenic lipoprotein profile, greater LDL oxidative susceptibility, lower plasma α-tocopherol levels, and greater early aortic atherosclerosis compared to semipurified diets.

Vitamin E reduces plasma low density lipoprotein cholesterol, LDL oxidation, and early aortic atherosclerosis compared with black tea in hypercholesterolemic hamsters

Abstract Dietary intakes of tea polyphenols have been reported to be inversely associated with the development of coronary heart disease via decreased LDL oxidation. Eighty male F 1 B Golden Syrian hamsters, 7 weeks of age, were divided into 4 groups of 20. The hamsters were fed a semi-purified hypercholesterolemic diet containing 12% coconut oil, 3% sunflower oil, and 0.2% cholesterol (w/w) (CONTROL), and either CONTROL + 0.625% brewed black tea (w/w) (LOW TEA), CONTROL + 1.25% brewed black tea (w/w) (HIGH TEA), or CONTROL + 0.044% tocopherol acetate (w/w) (VITAMIN E) for 10 weeks. The hamsters fed the VITAMIN E diet compared to the CONTROL, LOW TEA, and HIGH TEA diets had significantly lower plasma LDL-C concentrations (−18%, p

Robustness of chemometrics-based feature selection methods in early cancer detection and biomarker discovery

Abstract In omics studies aimed at the early detection and diagnosis of cancer, bioinformatics tools play a significant role when analyzing high dimensional, complex datasets, as well as when identifying a small set of biomarkers. However, in many cases, there are ambiguities in the robustness and the consistency of the discovered biomarker sets, since the feature selection methods often lead to irreproducible results. To address this, both the stability and the classification power of several chemometrics-based feature selection algorithms were evaluated using the Monte Carlo sampling technique, aiming at finding the most suitable feature selection methods for early cancer detection and biomarker discovery. To this end, two data sets were analyzed, which comprised of MALDI-TOF-MS and LC/TOF-MS spectra measured on serum samples in order to diagnose ovarian cancer. Using these datasets, the stability and the classification power of multiple feature subsets found by different feature selection methods were quantified by varying either the number of selected features, or the number of samples in the training set, with special emphasis placed on the property of stability. The results show that high consistency does not necessarily guarantee high predictive power. In addition, differences in the stability, as well as agreement in feature lists between several feature selection methods, depend on several factors, such as the number of available samples, feature sizes, quality of the information in the dataset, etc. Among the tested methods, only the variable importance in projection (VIP)-based method shows complementary properties, providing both highly consistent and accurate subsets of features. In addition, successive projection analysis (SPA) was excellent with regards to maintaining high stability over a wide range of experimental conditions. The stability of several feature selection methods is highly variable, stressing the importance of making the proper choice among feature selection methods. Therefore, rather than evaluating the selected features using only classification accuracy, stability measurements should be examined as well to improve the reliability of biomarker discovery.

Biomolecular Self-Assembly of Quantum-Dot Composites

A biomimetic approach utilizing biomolecular self-assembly was used to tailor quantum-dot composites for use as nonlinear optical media. Yeast tRNA was utilized as an ion-exchange/nucleation site within a polymeric matrix (polyacrylamide). Cadmium ion-exchange and subsequent sulfide precipitation resulted in quantum-dot formation. Illumination of samples with an Argon laser (514 nm) utilizing the Z-scan measurement method resulted in χ 3 values of +3.7 ×10 −6 esu.

Physical property improvements of a pellicular biocatalyst

The thermal stability of an immobilization technique using a pellicular latex matrix was examined in a packed-bed column reactor. The stability was found to vary with liquid flow rate, the type of latex, temperature of operation, and the amount of yeast cells. Adjusting these parameters and introducing particulate inorganic fillers strengthened the latex matrix and improved the thermal stability. Optimization of this immobilization technique resulted in a procedure that allowed latex polymers to be mechanically stable at temperatures up to 50°C. The biological viability of this improved immobilization scheme was demonstrated through the production of L-aspartic acid by immobilized cells of E. coli.

Biomimetic Process for Preparing Magnetite Fibers

Two different biomimetic strategies were utilized in the formation of magnetite fibers. The first strategy utilized natural ( Sphaerotilus natans sheaths) or synthetic (hollow fibers) matrices for magnetite formation. The second strategy made use of an iron-hydroxide intermediate that was subsequently chemically converted to magnetite within the biomimetic matrix. The formation of magnetite was determined by both visual and x-ray diffraction analysis. This process has advantages over conventional routes because of the expense and handling problems associated with the production of ceramic whiskers and fibers. The magnetite formed by this process may prove to have unique properties due to its unusual fiber structure.