Biomedical subjects

Rafael Moreno

Publications and source records attributed to Rafael Moreno.

9 recordsLinked to original sources

PubMed2006

Simulation of habituation to simple and multiple stimuli.

Within the psychological literature there are a number of models that reproduce the defining properties of habituation to a single stimulus. However, most of them do not reproduce the phenomenon of dishabituation shown in empirical studies, consisting in the recovery of a stimulus previously habituated upon the appearance of a novel stimulus. The present work offers a model of habituation which, in addition to reproducing the basic properties of habituation to a stimulus, also does so when more than one stimulus is presented, and thus includes the dishabituation phenomenon. This model consists of two functions, one called "activation" and the other "availability", and is tested by means of simulation of the responses in the context of different stimulus patterns. The results of the simulation show a good qualitative fit to the empirical results on the phenomena of habituation, including dishabituation. In addition, the model is suitable for inclusion in associative models that reproduce classical conditioning, which will make it possible in the future to incorporate into these in a simple way the influence that the habituation of each stimulus may have on its association with other stimuli.

Algorithms↗

PubMed2006

A single nucleotide polymorphism of the apolipoprotein A-V gene -1131T>C modulates postprandial lipoprotein metabolism.

The Apolipoprotein A-V (apoA-V) gene promoter polymorphism -1131T>C modulates triacylglycerol (TG) concentrations. We evaluate whether this polymorphism could be involved in the interindividual variability observed during postprandial lipemia. Fifty-one healthy apo E3E3 male volunteers [12 with -1131CC/CT genotype, and 39 with -1131TT genotype] underwent a Vitamin A fat-load test consisting of 1g of fat/kg body weight and 60,000IU of Vitamin A. Blood samples were taken at time 0 and every hour until the 6th and every 2h and 30 min until the 11th. Cholesterol (Chol) and TG were determined in plasma and Chol, TG, ApoB-100, ApoB-48, and retinyl palmitate (RP) were determined in lipoprotein fractions. Data of postprandial lipemia revealed that subjects with the -1131CT/CC genotype had a higher postprandial response of total plasma TG (p=0.043), large triacylglycerol-rich lipoproteins-TG (TRL-TG) (p=0.002), large TRL-Chol (p=0.004), small TRL-Chol (p=0.004) and small TRL-RP (p=0.001) than subjects with the -1131TT genotype. The modifications observed in postprandial lipoprotein metabolism in subjects with the apoA-V -1131T>C polymorphism could be involved in the increased fasting plasma TG concentrations previously described in carriers of the C allele.

Adolescent↗

PubMed2006

The Mediterranean and CHO diets decrease VCAM-1 and E-selectin expression induced by modified low-density lipoprotein in HUVECs.

BACKGROUND AND AIM: The oxidative modifications of low-density lipoprotein (LDL) are crucial for the atherosclerosis process. The aim of this study was to determine if the minimally modified LDL, obtained after the ingestion of three different diets, produce differential effects on the vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression in human umbilical endothelial cells (HUVECs). METHODS AND RESULTS: Twenty healthy young males were exposed to three dietary periods. Each period lasted four weeks. During the first period, all subjects consumed a saturated fat (SFA) enriched diet (38% fat, 20% SFA). The second and third dietary periods were administered following a randomized crossover design: a low fat high carbohydrates diet (CHO diet) and a Mediterranean diet. LDL particles, isolated during each dietary period, were oxidized by exposure to UV light and incubated for 48 h with HUVEC. Thereafter, 100 U/mL of TNF-alpha was added and incubation continued for 6 h. Cellular ELISA determined adhesion molecules expression. Lag time, propagation rate and total amounts of formed conjugated dienes were calculated in LDL incubated with 10mumol/L Cu(2+). When compared to the SFA diet, LDL isolated from the Mediterranean and CHO diets induced a lower expression of VCAM-1 and E-selectin in HUVECS (P<0.007). There were no differences between both lipid lowering diets. However, lag time of LDL from the Mediterranean diet was higher than with the CHO diet (P<0.042). This parameter was inversely correlated with E-selectin expression (r=-0.497; P<0.04). CONCLUSION: Our results suggest that both the Mediterranean and CHO diets may decrease the pro-inflammatory environment induced by modified LDL in endothelial cells.

Adult↗

PubMed2005

Simulation of the filtering role of habituation to stimuli.

In the context of a medium-term study designed to integrate the simulation of different types and processes of learning-such as classical, operant, and some cognitive types--one must start with other more elementary ones that are facilitators of the more complex types and processes. Of special interest is habituation, owing to the filtering out of irrelevant stimuli, which means that the simulated agent does not have to respond to them. This paper presents two difference functions constructed to computationally simulate the characteristics that define habituation. The behavior of these functions is described, as are differences arising from stimulus intensity and interstimulus intervals. Results are compared with existing empirical data.

Animals↗

PubMed2005

The apolipoprotein E gene promoter (-219G/T) polymorphism determines insulin sensitivity in response to dietary fat in healthy young adults.

Insulin sensitivity (IS) is determined by genetic and environmental factors, including diet. The apoE gene promoter -219G/T polymorphism is associated with coronary heart disease and increased postprandial triacylglycerol-rich lipoprotein concentration, circumstances related to insulin resistance. Thus, our aim was to determine whether this polymorphism modified the IS response to dietary fat in healthy young adults. Volunteers (n = 43) with the apoE3/E3 genotype (8 GG, 25 GT and 10 TT) completed 3 dietary periods, each lasting 4 wk. They first consumed a SFA-rich diet [38% fat (% of energy in the total diet), 20% SFA (% of energy in the total diet)], and then, in a randomized, crossover design, a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat, 22% MUFA). After each diet period, we investigated peripheral IS using the insulin suppression test. The steady-state plasma glucose (SSPG) concentration was lower (P < 0.05) in GG subjects than in GT and TT individuals, regardless of the diet consumed. Significant diet x genotype interactions were found for SSPG and plasma nonesterified FFA (NEFA) concentrations. Thus, the shift from the SFA-rich diet to the MUFA- or CHO-rich diets decreased (P < 0.05) the SSPG and NEFA concentrations in GG and GT, but not in TT subjects. In conclusion, carriers of the -219T allele are less insulin sensitive than GG individuals. Furthermore, only carriers of the -219G allele have improved IS when MUFA- or CHO-rich diets are consumed instead of a SFA-rich diet.

Adult↗

PubMed2004

Influence of the -514C/T polymorphism in the promoter of the hepatic lipase gene on postprandial lipoprotein metabolism.

The -514C/T polymorphism located in the promoter region of the hepatic lipase gene mediates changes in the plasma levels of the enzyme. The aim of this study was to determine whether the presence of this polymorphism modifies the postprandial clearance of lipoproteins of intestinal origin. 51 normolipemic volunteers, homozygotes for the allele E3 of the apo E were selected (26 homozygotes for the C allele and 25 carriers of the T allele in both homozygote and heterozygote form). The subjects underwent a Vitamin A fat-loading test. Blood was drawn every hour until the 6th hour and every 2 h and 30 min until the 11th hour to determine cholesterol and plasma triglycerides as well as cholesterol, triglycerides (TG) and retinyl palmitate in triacylglycerol-rich lipoproteins (chylomicrons and chylomicron remnants). Carriers of the T allele showed significantly lower postprandial levels of apolipoprotein B (P < 0.01), total TG in plasma (P < 0.05), small TRL-TG (P < 0.04), large TRL-TG (P < 0.04) and small TRL-cholesterol (P < 0.04) when compared to subjects homozygous for the C allele. Our data suggest that the T allele of the -514C/T polymorphism in the promoter region of the hepatic lipase gene is associated with a lower postprandial lipemic response.

Adult↗

PubMed2004

Apolipoprotein E gene promoter -219G->T polymorphism increases LDL-cholesterol concentrations and susceptibility to oxidation in response to a diet rich in saturated fat.

BACKGROUND: The apolipoprotein E (APOE) gene promoter polymorphism (-219G-->T) has been associated with increased risk of myocardial infarction, premature coronary artery disease, and decreased plasma apolipoprotein E concentrations. OBJECTIVE: We aimed to determine in healthy subjects whether this polymorphism modifies the susceptibility of LDL to oxidation and the lipid response to the content and quality of dietary fat. DESIGN: Fifty-five healthy men with the APOE3/E3 genotype (7 GG, 38 GT, and 10 TT) completed 3 dietary periods, each lasting 4 wk. The first was a saturated fatty acid (SFA)-rich diet [38% fat-20% SFA and 12% monounsaturated fatty acid (MUFA)-and 47% carbohydrates (CHO)], which was followed by a CHO-rich diet (30% fat-<10% SFA and 12% MUFA-and 55% CHO) or a MUFA-rich diet (38% fat-<10% SFA and 22% MUFA-and 47% CHO) in a randomized crossover design. At the end of each dietary period, LDL oxidation susceptibility, lipids, and lipoproteins were measured. RESULTS: Compared with carriers of the G allele, TT subjects had a significantly (P < 0.05) shorter lag time after the SFA diet. The replacement of the SFA diet by the CHO or MUFA diet induced a greater increase (P < 0.05) in lag time in the TT subjects than in the GG or GT subjects. Carriers of the T allele had higher LDL-cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) plasma concentrations after the SFA diet than did GG subjects. Compared with GG subjects, carriers of the T allele had a significantly (P < 0.05) greater decrease in LDL cholesterol and apolipoprotein B when they changed from the SFA to the CHO diet. CONCLUSION: The -219G-->T polymorphism may partially explain differences in individual responses to diet.

Apolipoprotein E3↗

PubMed2004

The effect of dietary fat on LDL size is influenced by apolipoprotein E genotype in healthy subjects.

LDL particle size is dependent on both genetic factors and environmental factors such as dietary fat composition. The apolipoprotein E (apoE) genotype is a major genetic determinant of LDL size. Thus, the aim of this work was to study whether the apoE genotype interacts with the quantity and quality of dietary fat, modifying LDL size in young healthy subjects. Healthy subjects (n = 84; 66 apoE 3/3, 8 apoE 4/3, 10 apoE 3/2) were subjected to 3 dietary periods, each lasting 4 wk. The first was an SFA-enriched diet (38% fat, 20% SFA), which was followed by a carbohydrate (CHO)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA) olive oil-rich diet (38% fat, 22% MUFA) following a randomized crossover design. At the end of each diet period, LDL particle size and plasma levels of total cholesterol, LDL cholesterol (LDL-C), HDL-C, apoB, apoA-I, and triacylglycerols were determined. LDL particle size was significantly higher (P < 0.04) in subjects with the apoE 4/3 genotype compared with those with apoE 3/3 and apoE 3/2 in the basal state. LDL size was smaller (P < 0.02) after the CHO diet than after the MUFA or SFA diets. After the CHO diet, a significant increase in LDL particle size (P < 0.035) was noted with respect to the MUFA diet in apoE 4/3 subjects, whereas a significant decrease was observed in the apoE 3/3 individuals (P < 0.043). In conclusion, a Mediterranean diet, high in MUFA-fat increases LDL particle size compared with a CHO diet, and this effect is dependent of apoE genotypes.

Adult↗

PubMedDate not supplied

Feasibility of retroviral vector-mediated in utero gene transfer to the fetal rabbit.

OBJECTIVES: Successful treatment or prevention of severe hereditary diseases could conceivably be achieved by genetic intervention early in development. Viral vector-mediated fetal gene transfer is proving a valuable tool to test the above concept in relevant animal models. Although the pregnant rabbit is a well-recognized model for fetal therapy, few preclinical assays have used it to validate fetal gene transfer approaches. In this preliminary study we assessed for the first time the feasibility of retroviral vector-mediated in utero gene transfer in the fetal rabbit. METHODS: Different amounts of the vesicular stomatitis virus G pseudotyped MFG(nls)LacZ retroviral vector, expressing a nuclear-localized beta-galactosidase reporter protein were injected intraperitoneally and -hepatically into 20- to 22-day-old fetuses. At 8-9 days post-treatment, the pups were sacrificed and the tissues harvested for analysis. Evidence of gene transfer was obtained by PCR amplification of proviral sequences within genomic DNA isolated from the treated samples. Transgenic beta-galactosidase expression was assessed by X-gal histochemical staining. RESULTS: By intraperitoneal injection 43% of the viable fetuses treated (3/7) showed evidence of successful LacZ gene transfer and low-level beta-galactosidase expression into liver and heart, whereas by intrahepatic injection roughly 38% (3/8) of the livers were positive for LacZ gene transfer and expression. The success rate for the viable fetuses rose to 67% positive livers (4/6) when a near double amount of recombinant virus was injected using a 10-fold concentrated virus stock. In terms of short-term safety, fetal and maternal survival rates approached 80% of treated fetuses, and 100% of treated does. CONCLUSIONS: The pregnant rabbit is a useful and reliable model allowing the design of further studies to optimize the conditions for effective, safer, and persistent retroviral vector-mediated fetal gene transfer.

Animals↗