Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial.

BACKGROUND AND AIM: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. METHODS AND RESULTS: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta = 4.84; 95% CI: 0.57-9.10). CONCLUSIONS: TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO.

Comparative effect of two Mediterranean diets versus a low-fat diet on glycaemic control in individuals with type 2 diabetes.

BACKGROUND/OBJECTIVES: Although benefits have been attributed to the Mediterranean diet, its effect on glycaemic control has not been totally elucidated. The aim of this work was to compare the effect of two Mediterranean diets versus a low-fat diet on several parameters and indices related to glycaemic control in type 2 diabetic subjects. SUBJECTS/METHODS: A multicentric parallel trial was conducted on 191 participants (77 men and 114 women) of the PREDIMED study in order to compare three dietary interventions: two Mediterranean diets supplemented with virgin olive oil (n=67; body mass index (BMI)=29.4±2.9) or mixed nuts (n=74; BMI=30.1±3.1) and a low-fat diet (n=50; BMI=29.8±2.8). There were no drop-outs. Changes in body weight and waist circumference were determined. Insulin resistance was measured by HOMA-IR index, adiponectin/leptin and adiponectin/HOMA-R ratios after 1 year of follow-up. RESULTS: Increased values of adiponectin/leptin ratio (P=0.043, P=0.001 and P<0.001 for low-fat, olive oil and nut diets, respectively) and adiponectin/HOMA-IR ratio (P=0.061, P=0.027 and P=0.069 for low-fat, olive oil and nut diets, respectively) and decreased values of waist circumference (P=0.003, P=0.001 and P=0.001 for low-fat, olive oil and nut diets, respectively) were observed in the three groups. In both Mediterranean diet groups, but not in the low-fat diet group, this was associated with a significant reduction in body weight (P=0.347, P=0.003 and P=0.021 for low-fat, olive oil and nut diets, respectively). CONCLUSIONS: Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet.

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study.

BACKGROUND AND AIMS: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. METHODS AND RESULTS: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02). CONCLUSION: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations.

Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: the PREDIMED study.

BACKGROUND AND AIMS: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. METHODS AND RESULTS: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55-80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820 ± 323 mg day⁻¹ (443 ± 218 mg day⁻¹ of flavonoids and 304 ± 156 mg day⁻¹ of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. CONCLUSION: In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil.

Triacylglycerol-rich lipoproteins derived from healthy donors fed different olive oils modulate cytokine secretion and cyclooxygenase-2 expression in macrophages: the potential role of oleanolic acid.

PURPOSE: Current evidence suggests that consumption of virgin olive oil (VOO) helps to protect against the development of atherosclerosis and that minor components such as oleanolic acid contribute to this effect. In this study, the effects of triacylglycerol-rich lipoproteins (TRLs) derived from olive oil on inflammatory processes in macrophages and how they are modulated by oleanolic acid was investigated. METHODS: TRLs isolated from healthy volunteers 2 and 4 h after a test meal containing VOO, pomace olive oil (POO) (the second pressing of olive oil, enriched in minor components) or POO enriched with oleanolic acid (OPOO) were incubated with macrophages derived from the human monocyte cell line, THP-1. RESULTS: All types of TRLs caused a decrease of about 50% in the secretion of monocyte chemoattractant protein-1 (MCP-1) by the cells. Interleukin (IL)-6 secretion was also significantly decreased by 2 and 4 h VOO TRLs and by 4 h OPOO TRLs. In contrast, increased IL-1ß secretion was observed with all 2 h TRL types, and increased tumour necrosis factor-α (TNF-α) production with 2 h VOO and POO, but not OPOO, TRLs. TRLs isolated after 4 h, however, had no significant effects on TNF-α secretion and increased IL-1ß secretion only when they were derived from VOO. Cyclooxygenase-2 (COX-2) mRNA expression was strongly down-regulated by all types of TRLs, but protein expression was significantly depressed only by 4 h OPOO TRLs. CONCLUSION: These findings demonstrate that TRLs derived from olive oil influence inflammatory processes in macrophages and suggest that oleanolic acid may have beneficial effects.

Comparación de los costos reales anuales asociados al manejo ambulatorio de pacientes hipertensos del programa cardiovascular en el Hospital Comunitario de Bulnes con el pago de prestaciones de Fonasa / Cost of ambulatory care of hypertensive subjects in a community hospital (bulnes): comparison of activity associated costs to the national health fund (fonasa) estimated payments in the setting of a national cardiovascular care program

Antecedentes: El financiamiento de las prestaciones entregadas a los usuarios de atención primaria portadores de Hipertensión Arterial, esta determinado por un arancel definido por el Fondo Nacional de Salud (FONASA), el cual ha estimado montos a pagar a la institución prestadora, basados en estudios realizados a nivel nacional, los cuales difieren de las estimaciones de gasto real de cada prestación, para lo cual se hace necesario objetivar dicha diferencia de estimación a nivel local. Objetivo: Determinar los costos directos e indirectos reales de las prestaciones entregadas a los usuarios hipertensos de control ambulatorio en atención primaria de salud mediante la metodología de costos asociados a actividades (ABC), para compararlos con los valores asignados por FONASA. Diseño: Estudio Analítico no experimental de enfoque cuantitativo de corte transversal, en que se revisaron 290 tarjetas de control de usuarios hipertensos bajo control en el Hospital Comunitario de Salud Familiar de Bul-nes. Se analizaron específicamente los valores del control Médico, control Enfermera, control Nutricionista, y valores de exámenes: hematocrito, perfil lipídico, glicemia, creatinina plasmática, orina completa, potasio plasmático, electrocardiograma, atención farmacéutica. Resultados: Los costos reales de las prestaciones incluidas en la Guía Clínica GES para el manejo ambulatorio de la Hipertensión Arterial, obtenidos mediante el uso de la metodología ABC fueron significativamente mayores a los establecidos por el FONASA (promedio miles de pesos: Fonasa 21.370; Costo real 39.991,7 +/- 11.999,4; p <0,001). Conclusión: Estos resultados sugieren que existe una diferencia entre lo que FONASA cancela por estas prestaciones y el gasto real en que se incurre por su atención. Si estos valores se acercan, podría obtenerse un mejor financiamiento del programa.

Background: Payments for ambulatory care of hypertensive patients in the national cardiovascular program is defined by FONASA based on national studies. Considerable differences are observed upon confrontation with the real costs involved in a given place. Aim: to determine direct and indirect costs of health care actions in the ambulatory care of hypertensive patients through an activity based cost (ABC) methodology and to compare these with the corresponding payments defined by FONASA Method: In a cross sectional design, 290 records of hypertensive subjects under control at the Community Hospital in Bulnes were analyzed. Costs of doctor, nurse and nutritionist controls were determined along with those related to laboratory tests including hematocrit, lipid profile, glycemia, plasma creatinine, urine analysis, plasma K level and electrocardiogram. Cost of pharmacy was also included. Results: a monthly mean of $ 39 992 +/- 12 000 per hypertensive patient cared was determined through ABC based costs. This is considerable greater than de $ 21 370 determined by FONASA (p<0.001). Conclusion: Payments considered by FONASA are insufficient to cover real costs involved in ambulatory care of hypertensive patients. A better financing of the cardiovascular care program requires these costs and payments to converge.

Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk.

BACKGROUND AND AIMS: Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. METHODS AND RESULTS: Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin-Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), coffee or wine after adjusting for potential confounders. The intake of 100 g of F&V (Beta=0.150;P<0.001) had a greater contribution to TPE than 100 mL of coffee (Beta=0.141;P=0.001), and the latter two foods contributed more than the consumption of 100 mL of wine (Beta=0.120;P=0.019). An inverse association was observed between urinary TPE and the prevalence of hypertension. Participants in the highest quartile of urinary TPE had a reduced prevalence of hypertension compared to those in the lowest quartile (Odds Ratio=0.64; 95% confidence interval 0.45 to 0.92; P=0.015). Systolic and diastolic BP were inversely associated with urinary TPE after adjustment for potential confounders (P=0.024 and P=0.003, respectively). CONCLUSIONS: Polyphenol intake, assessed via TPE in urine, was negatively associated with BP levels and prevalence of hypertension in an elderly Mediterranean population at high cardiovascular risk. Participants with the highest intake of polyphenol-rich foods showed the lowest BP measurements.

Manejo de las secreciones en pacientes con enfermedades neuromusculares / Management of secretions in patients with neuromuscular diseases

Introducción. Existe un amplio espectro de patologías incluidas dentro de las denominadas enfermedades neuromusculares (ENM). Pese a que existe una gran variabilidad interindividual, todas ellas se caracterizan por presentar un deterioro más o menos progresivo de la musculatura respiratoria. Sabemos que, en algunas de ellas, el tratamiento con ventilación no invasiva (VNI) ha modificado sustancialmente el pronóstico vital de estas enfermedades. Sin embargo, la imposibilidad de toser y, con ello, la incapacidad para eliminar las secreciones respiratorias puede desencadenar un fracaso respiratorio, poniendo en evidencia la debilidad muscular que sufren estos pacientes. Por dicho motivo, el especialista debería conocer cuáles son las causas que pueden ocasionar un mal manejo de secreciones en las ENM y saber utilizar las terapias con las que cuanta para solventarlas. No obstante, los estudios que miden la eficacia de dichas terapias son escasos, incluyen a un número discreto de pacientes, la mayoría de las veces con ENM muy heterogéneas (AU)

Introduction. There is an wide spectrum of diseases included within the so-called neuromuscular diseases (NMD). Even though there is a large interindividual variability, all of them are characterized by having a more or less progressive deterioration of the respiratory muscles. We know that non-invasive ventilation treatment (NIV) in some of them has substantially modified the vital prognosis of these diseases. However, inability to cough and thus incapacity to eliminate respiratory secretions may precipitate respiratory failure, showing the muscular weakness suffered by these patients. Thus, the specialist should know what the causes that may lead to poor management of secretions in NMD are and know how to use the therapies available in order to solve them. However, the studies that measure the efficacy of these therapies are limited. They included a small number of patients and most of them including very heterogeneous NMD (AU)

Interest of the association retinaldehyde/glycolic acid in adult acne.

BACKGROUND: Topical retinoids have been successfully used in the treatment of acne vulgaris but may induce irritation when used twice daily. The association of retinaldehyde (RAL) with glycolic acid (GA) have complementary activities, which could be of interest for adult women with acne because of a better tolerance/efficacy ratio. The aim of this study was to evaluate the tolerance and the efficiency of RAL (0.1%)/GA (6%) in adult women with acne when used alone or in combination with their usual acne products except retinoids. METHODS: Three hundred ninety-seven women with acne (aged between 30 and 40 years old) were included in this open multicentric study. They had to apply cream containing RAL/GA for 90 days without stopping their previous acne treatment (except topical retinoids). The tolerance was the main criteria and the second one is the efficacy, which was assessed by counting inflammatory and retentional lesions after 30 and 90 days of treatment. RESULTS: Used alone or in association with other anti-acne treatments, RAL/GA was considered to be highly tolerated. A significant decrease in both inflammatory and retentional lesions between day 0 and day 90 indicates that RAL/GA can be used as monotherapy for mild acne or could potentate the efficiency of other anti-acne products used at the same time by patients suffering from moderate acne. Complaints about side-effects were rare. The subjective evaluation of the preparation's efficacy by investigators and patients was strongly favourable. CONCLUSION: These data show that a combination of RAL 0.1% and GA 6% may be used in association with other topical anti-acne treatments with an excellent tolerance.

Oleanolic acid induces relaxation and calcium-independent release of endothelium-derived nitric oxide.

BACKGROUND AND PURPOSE: The present study investigated the mechanisms by which oleanolic acid, a component of olive oil, increases release of nitric oxide (NO). EXPERIMENTAL APPROACH: Measurements of isometric tension, NO concentration, or endothelial cell calcium were made in rat isolated mesenteric arteries. Immunoblotting for endothelial NOS (eNOS) and Akt kinase were performed in primary cultures of human umbilical vein endothelial cells (HUVECs). KEY RESULTS: Oleanolic acid (3-30 microM) evoked endothelium-dependent relaxations in noradrenaline-contracted rat superior and small mesenteric arteries. In rat superior mesenteric arteries, oleanolic acid induced simultaneous increases in NO concentration and relaxation, and these responses were inhibited by an inhibitor of NOS, asymmetric dimethyl-L-arginine (300 microM) and by the NO scavenger, oxyhaemoglobin (10 microM). Oleanolic acid-evoked NO increases were not reduced in Ca(2+)-free solution and in the presence of an inhibitor of endoplasmic reticulum calcium-ATPase, thapsigargin (1 microM). Oleanolic acid evoked relaxation without changes in endothelial cell calcium, but decreased smooth muscle calcium in arterial segments. Oleanolic acid failed to increase calcium in HUVECs, but increased time-dependently phosphorylation of Akt kinase at Serine(473) (Akt-Ser(473)) and eNOS at Serine(1177) (eNOS-Ser(1177)), which was attenuated by inhibitors of phosphoinositide-3-kinase. CONCLUSIONS AND IMPLICATIONS: This study provides direct evidence that a component of olive oil, oleanolic acid, activated endothelium-dependent release of NO and decreased smooth muscle cell calcium followed by relaxation. The oleanolic acid-evoked endothelium-derived NO release was independent of endothelial cell calcium and involved phosphoinositide-3-kinase-dependent phosphorylation of Akt-Ser(473) followed by phosphorylation of eNOS-Ser(1177).

Influence of minor components of olive oils on the composition and size of TRLs and on macrophage receptors involved in foam cell formation.

Metabolic and epidemiologic studies support the idea that the type of dietary fat is more important than the total amount of fat with respect to the development of atherosclerosis and the risk of cardiovascular heart disease. Dietary fat is carried in CMs (chylomicrons), which can be taken up by macrophages without need of further oxidation, leading to the formation of foam cells and initiating or aggravating the atherogenic process. Evidence from different studies has shown that dietary fat can influence the composition and size of TRLs (triacylglycerol-rich lipoproteins), which might modulate their atherogenicity to a certain extent. In particular, experiments in vitro have shown the anti-atherogenic effects of minor components from olive oil when forming part of TRL, as these particles give minor lipid components the opportunity to interact with the cells implicated in endothelial dysfunction and atherogenesis. However, the exact mechanisms mediating CM uptake by macrophages still remain unclear. Thus further studies are needed to understand how the modifications of TRL composition caused by dietary fats could modulate the expression of macrophage receptors and foam cell formation, or even improve the atherogenic risk of these particles.

Estudio de las repercusiones clínicas y analíticas de una intervención nutricional en pacientes no hospitalizados con claudicación intermitente. Estudio aleatorio controlado / A study of the clinical and analytical repercussions of a nutritional intervention in non-hospitalised patients with intermittent claudication. A controlled randomised study

Introducción. La dieta es un pilar fundamental, a veces olvidado, en el control y tratamiento de la enfermedad vascular periférica (EVP). Objetivo. Estudiar los efectos de la ingesta de ciertos nutrientes con probado efecto beneficioso en la prevención de la enfermedad coronaria en la clínica y el perfil bioquímico de enfermos claudicantes. Pacientes y métodos. Estudio longitudinal, descriptivo, aleatorio y doble ciego, con 60 varones claudicantes (grado IIB de Fontaine), distribuidos en dos grupos. Grupo I (n = 30): además de su dieta habitual consumieron 500 mL/día de leche semidesnatada adicionada de ácidos eicosapentanoico, docoxahexanoico, oleico y fólico y vitaminas A, D, E y B6. Grupo C (n = 26): además de su dieta habitual consumieron 500 mL/día de leche semidesnatada. Ambos grupos obtuvieron los mismos consejos higienicodietéticos, un antiagregante plaquetario (triflusal) y un hemorreológico (pentoxifilina). Con control trimestral, la intervención duró 12 meses. En cada control se realizó una exploración clínica vascular, claudicometría, índice de Yao, placetismografía y analítica. Resultados. La concentración plasmática de los nutrientes suministrados aumentó en el grupo I (p < 0,05), seguido de un descenso en colesterol total y la concentración de apolipoproteína B. La homocisteína total disminuyó en aquellos pacientes con hiperhomocisteinemia (p < 0,01). Paralelamente, la distancia de claudicación triplicó su valor (p < 0,001) y el índice de Yao aumentó de manera gradual (p < 0,05). Conclusiones. La inclusión diaria en la dieta de ciertos nutrientes cardiosaludables produjo, junto con otras recomendaciones dietéticas y hábitos de vida, una mejora significativa en los parámetros clínicos y analíticos de este grupo de claudicantes. La nutrición puede desempeñar un papel importante en el tratamiento y control de la EVP

INTRODUCTION. Diet is a sometimes neglected cornerstone in the control and treatment of peripheral vascular disease (PVD). AIMS. To study how the intake of certain nutrients with a proven beneficial effect in the prevention of heart disease affects the clinical symptoms and biochemical profile of patients with claudication. PATIENTS AND METHODS. A longitudinal, descriptive, randomised, double-blind study was conducted with 60 males with claudication (Fontaine grade IIB), distributed in two groups. Group I (n = 30): in addition to their usual diet, subjects consumed 500 ml/day of semi-skimmed milk with added eicosapentaenoic, docosahexaenoic, oleic and folic acids, as well as vitamins A, D, E and B6. Group C (n = 26): in addition to their usual diet, subjects consumed 500 mL/day of semi-skimmed milk. Both groups received the same hygienic-dietary guidelines, an antiplatelet drug (triflusal) and a haemorrheologic agent (pentoxifylline). Including a three-monthly control, the intervention lasted 12 months. At each control the following tests were carried out: vascular clinical examination, treadmill exercise testing, Yao index, plethysmography and analyses. RESULTS. The plasma concentration of the nutrients given to patients increased in group I (p < 0.05), followed by a decrease in total cholesterol and apolipoprotein B concentration. The total homocysteine level dropped in patients with hyperhomocysteinemia (p < 0.01). In a parallel fashion, the claudication distance become three times longer (p < 0.001) and the Yao index gradually increased (p < 0.05). CONCLUSIONS. Including certain nutrients that are good for the heart in the daily diet, along with other guidelines concerning nutrition and lifestyle, led to a significant improvement in the clinical and analytical parameters of this group of patients with claudication. Nutrition can play an important role in the treatment and control of PVD

Mola incompleta, eclampsia y síndrome de HELLP: un caso clínico / Partial mole, eclampsia and HELLP syndrome: a clinical case

Presentamos un caso clínico de mola parcial de 14 semanas, que debuta con crisis eclámptica y síndrome de HELLP. La paciente fue ingresada a la Unidad de Emergencia Obstétrica de nuestro hospital con crisis hipertensiva y eclámptica. Se realizó manejo de urgencia de la crisis eclámptica. La ecotomografía Doppler demostró feto único acorde a amenorrea, vivo y gran masa placentaria compuesta por infinidad de vesículas de aspecto hidatídico. La paciente evoluciona con un síndrome de HELLP, por lo que se decidió interrupción inmediata del embarazo por microcesárea tipo Pfannestiel, en la cual se extrajo gran masa placentaria molar y feto sin signos de vida. La paciente evolucionó favorablemente y fue dada de alta al décimotercer día postoperatorio. Se hace una discusión del caso.

International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

Dietary virgin olive oil triacylglycerols as an independent determinant of very low-density lipoprotein composition.

OBJECTIVE: We examined the effects of virgin olive oil (VOO) triacylglycerols (TGs) on the lipid composition of human very low-density lipoprotein (VLDL). METHODS: Twenty-one normocholesterolemic, normotensive, non-diabetic elderly subjects were recruited for the study. Two VOOs (VOO1 and VOO2) of the same variety, with an equivalent composition in minor components and differing only in the oleic and linoleic acid concentrations, were administered for 4 wk each to assess the effect of their TG molecular species compositions. Blood was collected after an overnight fast, VLDLs were isolated by ultracentrifugation, and lipid classes, TG molecular species, and TG fatty acid composition were determined. RESULTS: Dietary VOOs significantly differed in TG molecular species composition. VOO1 represented larger amounts of triolein (P < 0.01), whereas VOO2 was significantly enriched with dilinoleoyl-oleoyl-glycerol, linoleoyl-dioleoyl-glycerol, and linoleoyl-oleoyl-palmitoyl-glycerol (P < 0.01). For VLDL, intake of VOO1 caused an increase of total TG (P < 0.01) due mainly to increases in triolein and linoleoyl-dioleoyl-glycerol. Conversely, VOO2 increased VLDL cholesteryl esters (P < 0.01) and TG rich in arachidonic acid (P < 0.01). CONCLUSIONS: The different TG molecular species compositions of dietary oils may be an independent determinant of the lipid composition of VLDL in elderly people and therefore may play a role in regulating lipoprotein metabolism in these subjects.

Effects of different dietary oils on inflammatory mediator generation and fatty acid composition in rat neutrophils.

Virgin olive oil (VOO) compared with fish oil (FO) and evening primrose oil (PO) on the ability of stimulated leukocytes to produce inflammatory mediators was investigated in rats. Weaned Wistar rats were fed a basal diet (BD) (2% by weight of corn oil) or diets containing 15% by weight of VOO, PO, or FO. After 8 weeks, glycogen-elicited peritoneal polymorphonuclear leukocytes, mainly neutrophils, were isolated. The calcium-ionophore stimulated neutrophils (2.5 x 10(6) cells/mL) obtained from rats fed the different oils produced a higher release of lysosomal enzymes (beta-glucuronidase, lysozyme, and myeloperoxidase [MPO]) compared with those fed BD. The production of reactive oxygen species (ROS) in response to the stimulant, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), by neutrophils from the VOO group (15.44 nmol of O(2)(-) and 6.56 nmol of H(2)O(2)) was similar to the BD group (12.01 nmol O(2)(-) and 8.49 nmol H(2)O(2)) and significantly lower than the PO (20.90 nmol O(2)(-) and 10.84 nmol H(2)O(2)) and FO (20.93 nmol O(2)(-) and 12.79 nmol H(2)O(2)) groups. The cyclooxygenase-derived eicosanoid production was reduced by the lipid enrichment of the diets. Whereas the generation of prostaglandin E(2) (PGE(2)) was significantly decreased in VOO (5.40 ng/mL), PO (4.95 ng/mL), and FO (1.44 ng/mL) groups compared with BD (8.19 ng/mL), thromboxane B(2) (TXB(2)) reduction was especially significant in neutrophils from the FO diet group (14.67 ng/mL compared with 26.69 ng/mL from BD). These experimental data suggest that FO and PO, as well as VOO, could be considered a valuable strategy in preventing the generation of some inflammatory mediators.

Concentrations of exhaled nitric oxide in asthmatics and subjects with allergic rhinitis sensitized to the same pollen allergen.

BACKGROUND: Some studies have reported that the levels of exhaled nitric oxide (ENO) in asthmatics are similar to those in subjects with allergic rhinitis, and it has been postulated that atopic status might be the determinant of enhanced nitric oxide production in asthma. OBJECTIVES: The aim of this study was to determine differences in ENO levels between asthmatics and subjects with allergic rhinitis sensitized to the same allergen, and to correlate these levels with airway responsiveness. METHODS: Nineteen patients with asthma and 18 subjects with allergic rhinitis monosensitized to Parietaria pollen were enrolled in the study. ENO values and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured during the pollen season. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV1 (PC20). ENO was measured with the single-exhalation method. RESULTS: The geometric mean (95% confidence interval) ENO values were significantly higher in asthmatics than in subjects with allergic rhinitis: 72.4p.p.b. (54.9-93.3p.p.b) vs. 44.7p.p.b. (30.9-64.6p.p.b., P = 0.03). In asthmatics, a significant correlation was found between ENO and PC20 AMP values (p = -0.57, P=0.02), whereas no correlation was detected between ENO and PC20 methacholine (p = -0.35, P = 0.14). CONCLUSIONS: Our results suggest that atopy is not the only determinant of increased ENO levels detected in subjects with asthma, and that responsiveness to AMP may be a more sensitive marker for assessing airway inflammation in asthma compared to methacholine.

Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid sunflower) on vascular reactivity in Wistar-Kyoto and spontaneously hypertensive rats.

The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of vascular response from isolated thoracic rat aorta and lipid composition and fatty acid composition were studied and compared with samples from rats fed on a control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 weeks of age. The maximum contraction of aortic ring preparations in response to phenylephrine (10(-6) m) was significantly decreased in SHR rats fed with OO (0.81 (sem 0.05) v. 1.18 (sem 0.09) g, and treatment with HOSO did not alter the phenylephrine-induced contractions. The relaxant responses to acetylcholine (10(-5) m) were significantly enhanced (30.03 (sem 0.70) v. 18.47 (sem 0.28) %, in the rings from SHR rats treated with OO, and were more pronounced than in WKY rats In the same way, OO attenuated the dose-response curves induced by phenylephrine (10(-8)-10(-5) m) from SHR rats, accompanied with a slower contraction. These results suggest that only the chronic feeding of OO diet was able to attenuate the vascular response of rat aorta. In addition, an increase in phospholipid content (186.7 (sd 3.2) v. 159.1 (sd 11.3) g/kg, and changes in the fatty acid composition of aorta (mainly a decrease in arachidonic acid) could contribute to improving endothelial function. Therefore, the effects can not be attributed exclusively to the content of MUFA (mainly oleic acid). Other components of OO, such as polyphenols, not present in HOSO, may help to explain the vascular protective effect of OO consumption.

Effects of virgin olive oil phenolics on scavenging of reactive nitrogen species and upon nitrergic neurotransmission.

The major phenolics from the polar fraction of virgin olive oil (caffeic acid, oleuropein, tyrosol and hydroxytyrosol) have well-established antioxidant activities but their effects on reactive nitrogen species and nitrergic neurotransmission have not been fully investigated. The three catechol compounds were active as scavengers of nitric oxide generated spontaneously from the decomposition of sodium nitroprusside (approximately 50% inhibition achieved at 75 microM), and had similar ability to scavenge chemically generated peroxynitrite, as determined by an alpha1-antiproteinase inactivation assay (67.2%-92.4% reduction when added at 1 mM). Tyrosol was less active in these tests, but does not possess the catechol functionality. Despite their ability to interact with chemically prepared nitric oxide, neither oleuropein nor hydroxytyrosol at 5 microM altered NO*-mediated relaxations of the nerve-stimulated rat anococcygeus preparation, but this may be because the nitrergic transmitter is protected from the effects of externally applied scavengers. In conclusion, the phenolics found in virgin olive oil possess ability to scavenge reactive oxygen and nitrogen species that are implicated in human pathologies, but their impact may be restricted to those species present in the extracellular environment.

Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin olive oil diet.

OBJECTIVE AND DESIGN: The aim of the present study was to examine the effect of a virgin olive oil enriched diet in acute and chronic inflammation models in rats and to determine the effect of supplementing this oil with a higher content of its polyphenolic fraction. The response was compared to oils rich in monounsaturated fatty acids (high oleic sunflower oil and palm olein) and rich in polyunsaturated fatty acids (fish oil). DIETS: Groups of 6-8 male Wistar rats were fed from weaning on six purified diets differing in type of oil: 2% corn oil (basal diet, BD), 15% high oleic sunflower oil (HOSO), 15% virgin olive oil (VOO), 15% virgin olive oil supplemented with 600 p.p.m. polyphenols from this oil (PSVOO), 15% palm olein (POL), and 15% fish oil (FO). MATERIALS AND METHODS: Rats were fed for 8 weeks with BD, HOSO, VOO, PSVOO, POL and FO diets before injecting carrageenan. Rats were fed for 3 weeks with BD, PSVOO and FO diets before induction of adjuvant arthritis. Dietary treatment with or without indomethacin continued during 3 weeks. The data were evaluated using an analysis of variance (ANOVA) followed by the least-significant differences. RESULTS: In carrageenan oedema test, the inflammation indices of animals fed on a diet rich in olive oil (VOO) were lower compared to animals fed with oils high in oleic acid (HOSO, POL) and polyunsaturated fatty acids (FO), and markedly diminished in the group fed on PSVOO. In established adjuvant arthritis, the PSVOO diet was even more effective than FO diet in the prevention of inflammation. Both groups of animals showed an increase in weight during the latter days of the experiment compared to the BD. Indomethacin administered to every diet group, exerted a strong inhibitory effect on the inflammatory process throughout which was augmented by the PSVOO and FO diets. CONCLUSIONS: This study demonstrates that virgin olive oil with a higher content of polyphenolic compounds, similar to that of extra virgin olive oil, shows protective effects in both models of inflammation and improves the disease associated loss of weight. This supplementation also augmented the effects of drug therapy.