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Biomedical subjects

E Ros

Publications and source records attributed to E Ros.

At least 37 records · Page 2Linked to original sources

Walnut-enriched diet increases the association of LDL from hypercholesterolemic men with human HepG2 cells.

In a randomized, cross-over feeding trial involving 10 men with polygenic hypercholesterolemia, a control, Mediterranean-type cholesterol-lowering diet, and a diet of similar composition in which walnuts replaced approximately 35% of energy from unsaturated fat, were given for 6 weeks each. Compared with the control diet, the walnut diet reduced serum total and LDL cholesterol by 4.2% (P = 0.176), and 6.0% (P = 0.087), respectively. No changes were observed in HDL cholesterol, triglycerides, and apolipoprotein A-I levels or in the relative proportion of protein, triglycerides, phospholipids, and cholesteryl esters in LDL particles. The apolipoprotein B level declined in parallel with LDL cholesterol (6.0% reduction). Whole LDL, particularly the triglyceride fraction, was enriched in polyunsaturated fatty acids from walnuts (linoleic and alpha-linolenic acids). In comparison with LDL obtained during the control diet, LDL obtained during the walnut diet showed a 50% increase in association rates to the LDL receptor in human hepatoma HepG2 cells. LDL uptake by HepG2 cells was correlated with alpha-linolenic acid content of the triglyceride plus cholesteryl ester fractions of LDL particles (r(2) = 0.42, P < 0.05). Changes in the quantity and quality of LDL lipid fatty acids after a walnut-enriched diet facilitate receptor-mediated LDL clearance and may contribute to the cholesterol-lowering effect of walnut consumption.

Adult↗

Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. A randomized crossover trial.

BACKGROUND: It has been reported that walnuts reduce serum cholesterol levels in normal young men. OBJECTIVE: To assess the acceptability of walnuts and their effects on serum lipid levels and low-density lipoprotein (LDL) oxidizability in free-living hypercholesterolemic persons. DESIGN: Randomized, crossover feeding trial. SETTING: Lipid clinic at a university hospital. PATIENTS: 55 men and women (mean age, 56 years) with polygenic hypercholesterolemia. INTERVENTION: A cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced approximately 35% of the energy obtained from monounsaturated fat. Patients followed each diet for 6 weeks. MEASUREMENTS: Low-density lipoprotein fatty acids (to assess compliance), serum lipid levels, lipoprotein(a) levels, and LDL resistance to in vitro oxidative stress. RESULTS: 49 persons completed the trial. The walnut diet was well tolerated. Planned and observed diets were closely matched. Compared with the Mediterranean diet, the walnut diet produced mean changes of -4.1% in total cholesterol level, -5.9% in LDL cholesterol level, and -6.2% in lipoprotein(a) level. The mean differences in the changes in serum lipid levels were -0.28 mmol/L (95% CI, -0.43 to -0.12 mmol/L) (-10.8 mg/dL [-16.8 to -4.8 mg/dL]) (P<0.001) for total cholesterol level, -0.29 mmol/L (CI, -0.41 to -0.15 mmol/L) (-11.2 mg/dL [-16.3 to -6.1 mg/dL]) (P<0.001) for LDL cholesterol level, and -0.021 g/L (CI, -0.042 to -0.001 g/L) (P = 0.042) for lipoprotein(a) level. Lipid changes were similar in men and women except for lipoprotein(a) levels, which decreased only in men. Low-density lipoprotein particles were enriched with polyunsaturated fatty acids from walnuts, but their resistance to oxidation was preserved. CONCLUSION: Substituting walnuts for part of the mono-unsaturated fat in a cholesterol-lowering Mediterranean diet further reduced total and LDL cholesterol levels in men and women with hypercholesterolemia.

Algorithms↗

Effects of CI-1002 and CI-1017 on spontaneous synaptic activity and on the nicotinic acetylcholine receptor of Torpedo electric organ.

The effect of azepino[2,1-b]quinazoline 1,3-dichloro-6,7,8,9,10, 12-hexahydro-, mono-hydrochloride (CI-1002), a tacrine derivative, and 1-azabicyclo[2.2.1]heptan-3-one, O-[3-(methoxyphenyl)-2-propynyl]oxime [R-(Z)]-2-butenedioate (CI-1017), a muscarinic M(1) receptor agonist, on spontaneous synaptic activity was investigated by measuring amplitude, rise time, velocity of rising, half-width, and electrical charge of miniature endplate potentials (m.e.p.p.) recorded extracellularly in Torpedo electric organ fragments. The effect of CI-1002 and CI-1017 on the nicotinic acetylcholine receptor was investigated by measuring the current induced by acetylcholine in Xenopus laevis oocytes transplanted with membranes from Torpedo electric organ. CI-1002, at a concentration of 1 microM, altered the m.e.p.p. by increasing the amplitude (from 1.08+/-0.01 to 2.76+/-0.03 mV), rise time (from 0. 700+/-0.006 to 1.02+/-0.01 ms), rising rate (from 1.79+/-0.02 to 3. 45+/-0.05 mV/ms), half-width (from 0.990+/-0.008 to 2.40+/-0.02 ms), and electrical charge (from 304+/-4 to 784+/-11 mV s). CI-1017, at a concentration of 1 microM, altered the m.e.p.p. by decreasing the amplitude (from 1.08+/-0.01 to 0.650+/-0.007 mV), rise time (from 0. 700+/-0.006 to 0.530+/-0.007 ms), rising rate (from 1.79+/-0.02 to 1. 53+/-0.02 mV/ms), half-width (from 0.990+/-0.008 to 0.670+/-0.007 ms), and electrical charge (from 304+/-4 to 75+/-1 mV s). CI-1002 inhibited the acetylcholine-induced current of nicotinic acetylcholine receptors with an IC(50) of 3.4+/-0.3 microM. CI-1017 inhibited the acetylcholine-induced current of nicotinic acetylcholine receptors with an IC(50) of 0.8+/-0.1 microM. These results indicate that, although both drugs interacted negatively with nicotinic acetylcholine receptors, CI-1002 overcame this inhibition by recruiting more acetylcholine to build a quantum.

Animals↗

Mutation analysis in 36 unrelated Spanish subjects with familial hypercholesterolemia: identification of 3 novel mutations in the LDL receptor gene.

We used the single strand conformation polymorphism (SSCP) method to investigate 36 apparently unrelated Spanish patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequences of the low density lipoprotein receptor (LDLR) gene. Nineteen aberrant SSCP patterns were found, and the underlying mutations were characterized by DNA sequencing. In addition, we tested all patients for the presence of mutations in the gene coding for apolipoprotein B (apo B). Five missense mutations (Q71E, S156L, E256K, N543H and T705I), four nonsense mutations (W(-18)X, E10X, Q133X and C255X), six frameshift mutations (211delG, 518delG, 1045delC, 2085del19, 2207insT and 2393del9) and five splicing mutations (313+1G->C, 1061-8T->C, 1845+1G->C, 2140+5G->A and 2390-1G->C) were identified in the LDLR gene. In total, we detected 20 mutations, 3 of which, designated 1045delC, 1845+1G->C and 2207insT, have not been previously described. Seven patients were found to carry two different mutations in the same allele: W(-18)X and E256K (one patient), Q71E and 313+1G->C (two patients), 1061-8T->C and T705I (two patients), 518delG and 2140+5G->A (one patient) and N543H and 2393del9 (one patient). As we expected, there is a broad spectrum of mutations in the LDLR gene, given the genetic heterogeneity of the Spanish population.

Apolipoproteins B↗

Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk.

Triglycerides and cholesterol are important biological lipids, and their excessive intake in the diet is relevant to the development of two prevalent cardiovascular risk factors, obesity and hypercholesterolemia. Because most lipids are essentially water-insoluble molecules, their transport within and absorption from the aqueous medium of intestinal contents is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific esterases, micellar transport, mucosal absorption, re-synthesis of parent molecules in enterocytes, and assembly with apolipoproteins and other molecules to form chylomicrons, the secretory product of intestinal cells. Many of these processes, however, are not well characterized at the molecular level. While in health the intestinal absorption of triglycerides is very efficient, the same does not apply to cholesterol absorption. Besides being generally inefficient, cholesterol absorption is highly variable, with a between-subject variability that depends in part on genetic factors and an intra-individual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal lipid absorption can be interfered with by dietary components or drugs and thus are potential therapeutic targets for inducing a controlled malabsorption of triglyceride, useful in the treatment of obesity, or for rendering cholesterol absorption even more inefficient in an attempt to lower blood cholesterol levels. Nevertheless, intestinally derived cholesterol available to the liver exerts complex feedback regulation on whole-body cholesterol homeostasis that limits the efficacy of cholesterol absorption inhibitors to lower blood cholesterol. This review focuses first on present knowledge of the physiology of intestinal fat absorption, necessary to understand the ways to manipulate it in order to obtain the desired effects on dietary triglyceride and cholesterol disposition. The second part discusses old, present and future ways, both dietary and pharmacological. of interfering with cholesterol and triglyceride absorption to reduce blood cholesterol and energy acquisition, respectively.

Animals↗

Application of focused-microwave wet digestion to the determination of trace metals in human gallstones by ICP/AES.

We propose an analytical digestion method for trace metal determination (Co, Cr, Cu, Fe, Mn, Ni and Zn) in gallstones, in an attempt to facilitate detection of their origin. The method consists of sample digestion with HNO3 and H2O2 by means of focused microwave. Metals are quantified by inductively coupled plasma atomic emission spectroscopy. The effect of calcium concentration in the analytical solutions was studied. Cu, Fe, Mn and Zn were detected in all the samples analysed and the highest concentrations were obtained for Cu and Fe, especially in black-pigmented gallstones. The reproducibility in terms of %RSD, determined in the gallstones with the lowest metal content, was below 5% for Cu, between 10% and 15% for Mn and Zn and up to 25% for Fe.

Calcium↗

High-monounsaturated fat, olive oil-rich diet has effects similar to a high-carbohydrate diet on fasting and postprandial state and metabolic profiles of patients with type 2 diabetes.

Whether metabolic control in type 2 diabetes mellitus (DM) is best achieved with the traditional high-carbohydrate (CHO), low-fat diet or a low-CHO, high-fat diet is still controversial. In a randomized crossover study, we compared the effects of a low-fat (30% of daily energy) diet and a high-fat (40% of daily energy), high-monounsaturated-fat diet for 6 weeks each on fasting and postprandial glucose, insulin, and lipoprotein concentrations in 12 patients with well-controlled type 2 DM (fasting blood glucose, 176 +/- 54 mg/dL; hemoglobin A1c, 6.4% +/- 0.7%) and no overt dyslipidemia (serum total cholesterol, 235 +/- 43 mg/dL; triglycerides, 180 +/- 63 mg/dL). Home-prepared foods were used and olive oil was the main edible fat, accounting for 8% and 25% of daily energy requirements in the low-fat and high-fat diets, respectively. For postprandial studies, the same mixed meal containing 36% fat was used in both dietary periods. Body weight and fasting and 6-hour postprandial blood glucose, insulin, and lipoprotein levels were similar after the two diets. The mean incremental area under the curve of serum triglycerides 0 to 6 hours after the challenge meal, adjusted for baseline levels, did not change significantly after the high-fat diet compared with the low-fat diet (1,484 +/- 546 v 1,714 +/- 709 mg x 6 h/dL, respectively, P = .099). Mean postprandial triglyceride levels at 6 hours were increased about 2 times over fasting levels and were still greater than 300 mg/dL after either diet. A diet high in total and monounsaturated fat at the expense of olive oil is a good alternative diet to the traditional low-fat diet for patients with type 2 DM. However, ongoing postprandial hypertriglyceridemia with either diet points to the need for other therapies to decrease triglyceride-rich lipoproteins (TRL) and the inherent atherogenic risk in type 2 diabetics.

Diabetes Mellitus, Type 2↗

Rapid westernization of children's blood cholesterol in 3 countries: evidence for nutrient-gene interactions?

The aim of this study was to examine potential factors that modify blood cholesterol among children in countries in which dietary and lifestyle habits are becoming westernized. Population data on serum total and lipoprotein cholesterol, anthropometric indexes, and dietary intake were reviewed and compared for children aged 1-18 y from Japan, Spain, and the United States. The data show that total serum cholesterol in Japanese and Spanish children recently exceeded the 75th percentile for US children, primarily reflecting LDL cholesterol, although both LDL and HDL cholesterol contributed. Adiposity indexes do not explain the trends observed. Total and saturated fat intakes increased substantially in both Japan and Spain but in Japan are still lower than intakes in the United States. The Hegsted equation was used to relate differences in serum cholesterol to dietary fat intake. Changes in total serum cholesterol followed established dietary correlations among children in Spain, but not in Japan. Serum cholesterol in Japanese children was predicted to be 0.20-0.32 mmol/L lower than in US children; actual concentrations were considerably higher. These results suggest that a rapid westernization of children's blood cholesterol concentrations has occurred in Japan and Spain. Changes in fat intake predict changes in blood cholesterol in Spain, but not in Japan. Differences in genetic response to diet in certain populations, such as the Japanese, may explain higher blood cholesterol concentrations with lower fat intakes compared with the United States.

Adolescent↗

A quantitative study of fault tolerance, noise immunity, and generalization ability of MLPs

An analysis of the influence of weight and input perturbations in a multilayer perceptron (MLP) is made in this article. Quantitative measurements of fault tolerance, noise immunity, and generalization ability are provided. From the expressions obtained, it is possible to justify some previously reported conjectures and experimentally obtained results (e.g., the influence of weight magnitudes, the relation between training with noise and the generalization ability, the relation between fault tolerance and the generalization ability). The measurements introduced here are explicitly related to the mean squared error degradation in the presence of perturbations, thus constituting a selection criterion between different alternatives of weight configurations. Moreover, they allow us to predict the degradation of the learning performance of an MLP when its weights or inputs are deviated from their nominal values and thus, the behavior of a physical implementation can be evaluated before the weights are mapped on it according to its accuracy.

Journal Article↗

Randomized crossover study of gemfibrozil versus lovastatin in familial combined hyperlipidemia: additive effects of combination treatment on lipid regulation.

The most appropriate therapy for combined hyperlipidemia remains to be determined. We compared the lipid-regulating effects of gemfibrozil and lovastatin in 30 patients with familial combined hyperlipidemia (FCHL) in a randomized, double-blind, placebo-controlled crossover study including 8-week courses of one drug followed by a washout period and a crossover phase to the alternate drug. After completion of the trial, open-label combination therapy was given for up to 12 months. Lovastatin was more efficacious than gemfibrozil in the reduction of total cholesterol (23% v. 9%, P<.001) and low-density lipoprotein (LDL) cholesterol (28% v. 2%, P<.001), whereas gemfibrozil surpassed lovastatin in the reduction of triglycerides (48% v. 0%, P<.001) and very-low-density lipoprotein (VLDL) cholesterol (50% v. 19%, P = .005) and the increase of high-density lipoprotein (HDL) cholesterol (18% v. 4%, P = .005). Lovastatin caused a greater decline in total apolipoprotein B (apo B) and LDL apo B than gemfibrozil, whereas VLDL apo B decreased only after gemfibrozil therapy. Drug-induced changes in lipoprotein composition indicated that gemfibrozil reduced both the number and size of VLDL particles and lovastatin decreased the number of LDL particles. Combined treatment was safe and had additive effects on lipids, causing significant (P<.001) reductions in total cholesterol (32%), triglycerides (51%), LDL cholesterol (34%), and apo B (26%) and an increase in HDL cholesterol (19%). Target LDL cholesterol levels were achieved only in 11% of patients given gemfibrozil alone and triglycerides decreased to target levels in 22% after lovastatin alone, whereas combined therapy normalized both lipid fractions in 96% of patients. Thus, in FCHL, gemfibrozil has no effect on LDL cholesterol levels but favorably influences the putative atherogenic alterations of lipoprotein composition that are related to hypertriglyceridemia. Conversely, lovastatin markedly decreases LDL cholesterol but has little effect on triglyceride-rich lipoproteins. Combination treatment safely corrects all of the lipid abnormalities in most patients.

Adult↗

Lifestyle changes in free-living patients with peripheral vascular disease (Fontaine stage II) related to plasma and LDL lipid composition: a 15 month follow-up study.

Peripheral vascular disease (PVD) is characterized by arteriosclerosis and lower extremity ischemia which cause intermittent claudication. Patients grouped in the Fontaine stage II have more than 75% organic stenosis in their large coronary arteries and exhibit a number of alterations in blood coagulation and plasma lipids. The aim of this study was to evaluate an intervention program of lifestyle habits including dietary recommendations, moderate exercise and decreased smoking in a population of patients with PVD for a period of 15 months, with respect to plasma-lipid and lipoprotein composition as well as LDL susceptibility to peroxidation. These parameters are well known risk indicators of arteriosclerosis and coronary heart disease. A total 13 subjects diagnosed with PVD (Fontaine stage II) were selected, while a healthy age-matched group (n=20) was used as a reference. This study design was an uncontrolled trial of lifestyle interventions. The group of patients was examined at 0, 3, 6, 9, 12 and 15 months. Patients smoking one or more packets of cigarettes per day at the beginning of the study (54.2%) decreased smoking by as much as 7.7% 15 months later. In addition, physical activity intensified significantly (walking > 1 km: 13.1-77%) and treadmill running increased over the study period while the energy intake decreased by 10%. The percentage of saturated fat in the diet decreased by 10% while the intake of polyunsaturated fat rose, and monounsaturated-fat intake showed a parallel trend to increase; the average intake of cholesterol also fell by 10% and plasma triglycerides and HDL-cholesterol showed a trend to decrease and increase, respectively. No permanent changes in LDL lipid fractions for patients were detected during the follow-up period and no differences between patients and the age-matched reference group were found. The macrophage uptake of plasma-oxidized LDL was significantly higher in patients than in the reference group and no differences due to the intervention period were detected. In conclusion, the education in lifestyle and nutritional habits of patients with PVD led to reduced energy intake parallel with augmented physical activity as well to a fall in plasma triglycerides and a rise in HDL-cholesterol, which are good indicators of a reduced risk of vascular and myocardial complications.

Analysis of Variance↗

Effect of extra-virgin olive oil and fish-oil supplementation on plasma lipids and susceptibility of low-density lipoprotein to oxidative alteration in free-living spanish male patients with peripheral vascular disease.

The aim of this study was to analyse the in vivo effect of a diet rich in extra-virgin olive oil and a fish-oil supplement on plasma and lipoprotein fatty-acid composition and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease. A total of 12 patients were included in the experimental group which received extra virgin olive oil and a fish oil supplement (group OF). On the other hand, 13 patients which had refined olive oil as the main visible fat were considered as Control group. Plasma triglycerides decreased significantly after three months of dietary intervention. The LDL and plasma fatty-acid pattern in the group OF was characterized by a significant increase in n-3 polyunsaturated fatty acids, mainly 20:5 n-3 and 22:6 n-3. The slopes of LDL oxidative susceptibility were similar between baseline and endpoint values in both groups. However, the uptake of oxidized LDL by macrophages was significantly reduced in OF patients in comparison with the Control group. In conclusion, the daily intake of about 40 g/d of extra-virgin olive oil in combination with a daily supplement of 16 g of fish oil for 3 months in patients with peripheral vascular disease leads to a plasma-lipid profile less atherogenic than in patients having refined olive oil as the main visible food fat. The simultaneous consumption of alpha-tocopherol and natural antioxidants provided by extra-virgin olive oil seems to have a protective effect on the LDL susceptibility to oxidative modifications in spite of a higher proportion of n-3 polyunsaturated fatty acids.

Cholesterol, HDL↗

Olive oil- and fish oil-enriched diets modify plasma lipids and susceptibility of LDL to oxidative modification in free-living male patients with peripheral vascular disease: the Spanish Nutrition Study.

The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease (Fontaine stage II) were given specific lipid supplements. Designed as a longitudinal intervention study, patients were provided with olive oil for 3 months, followed by a 3 month wash-out period, then supplemented with a combination of fish oil and olive oil for the final 3 months. Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined. Furthermore, lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake. In addition, thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group. A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months. Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients. The intake of the fish-oil supplement resulted in significantly increased plasma levels of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) in comparison with baseline concentrations, olive-oil and control groups. Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period, control and reference groups. The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group, and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil. In conclusion, consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation.

Cholesterol, LDL↗

Extra-virgin olive oil increases the resistance of LDL to oxidation more than refined olive oil in free-living men with peripheral vascular disease.

Patients with peripheral vascular disease (Fontaine stage II) are characterized by ischemia of the lower extremities, atherosclerosis and alteration of blood coagulation and fibrinolysis. A randomized, two-period, crossover design was used to compare the effects of extra-virgin (VO) and refined olive (RO) oils on plasma lipids and lipoprotein composition and LDL oxidation susceptibility in free-living men with peripheral vascular disease. The oils differed in their antioxidant profile (alpha-tocopherol: 300 vs. 200 mg/kg; phenolic compounds 800 vs. 60) and concentration but not in their fatty acid composition. Subjects were randomly assigned to two groups. The first group (n = 12) received VO with which to freely cook all meals for 3 mo, followed by a 3-mo wash-out period; they then received RO for the final 3 mo. The second group (n = 12) consumed the oils in the opposite order. Energy, fat, polyunsaturated fatty acids (PUFA) and alpha-tocopherol intakes were not different when patients consumed the two oils. Profiles of the major fatty acids in plasma and LDL were not different after consumption of VO and RO. The slope of the line for LDL oxidation vs. the line for copper concentration was significantly higher after the intake of RO than after the intake of VO. Total LDL taken up by macrophages was significantly greater when the men consumed RO rather than VO. We suggest that antioxidants present in VO may protect LDL against oxidation more than does RO in men with peripheral vascular disease.

Aged↗