Pablo Strobel

Pontifical Catholic University of Chile, Santiago, Region Metropolitana de Santiago, Chile

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Publications (14)37.96 Total impact

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    ABSTRACT: Endothelial dysfunction is associated with atherogenesis and oxidative stress in humans. In rat and rabbit blood vessels, wine polyphenol antioxidants induce vascular relaxationin vitro through the NO-cGMP pathway. To assess the effect of a regular high-fat diet (HFD) and moderate red wine consumption on endothelial function (EF), a study was performed in healthy male volunteers. EF was measured as flow-mediated dilatation of the brachial artery, employing high-resolution ultrasound after an overnight fast. Other clinical and biochemical parameters related to EF were also measured. Six volunteers received a control diet, rich in fruits and vegetables (27% calories as fat) and five volunteers received an HFD (39.5% calories as fat). Measurements were done twice on each volunteer: after a period of 30 d with diet plus 240 mL of red wine/d, and after a period of 30 d with diet, without wine. In the absence of wine, there is a reduction of EF with HFD when compared to the control diet (P=0.014). This loss of EF is not seen when both diets are supplemented with wine for 30 d (P=0.001). Plasma levels ofn−3 fatty acids (R 2=0.232,P=0.023) and lycopene (R 2=0.223,P=0.020) show a positive correlation with individual EF measurements, but they do not account for the significant differences observed among dietary groups or after wine supplementation. These results help elucidate the deleterious effect of a high-fat diet and the protective role of wine, n−3 fatty acids and dietary antioxidants in cardiovascular disease.
    Lipids 04/2012; 35(2):143-148. · 2.56 Impact Factor
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    ABSTRACT: To assess the effect on oxidative damage of the administration of a Mediterranean diet (MD) compared with an Occidental diet (OD), in young adult volunteers, with or without the concomitant intake of red wine. Forty-two omnivorous male students 20-27 years old were given either diet for 3 months. During the first and third month they received the prepared diets alone but during the second month they also had 240 ml/day of red wine. Blood and urine samples were taken at 0, 30, 60, and 90 days for analyses. A linear mixed effect model was used to compare the effect of both diets and wine, controlling values by baseline measurements. MD increased plasma vitamin C, beta-carotene and total antioxidant reactivity (TAR). OD increased plasma vitamin E. Wine supplementation, analyzed combining both diet groups, raised plasma vitamin C, beta-carotene, uric acid, TAR, plasma and urinary polyphenols and decreased plasma vitamin E. Also wine intake increased concentration of red blood cell (RBC) glutathione while significantly decreasing plasma glutathione. In oxidative damage measurements OD group showed higher concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA from peripheral blood leukocytes and plasma nitrotyrosine, when compared with MD group. Wine intake significantly decreased 8-OHdG and plasma nitrotyrosine in both diets, particularly in OD. Volunteers on MD showed better antioxidant defenses and less oxidative damage than those on OD. Moderate wine consumption improved antioxidant defenses in both groups and counteracted the oxidative damage observed with OD.
    Atherosclerosis 04/2010; 211(2):694-9. · 3.71 Impact Factor
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    ABSTRACT: To evaluate the feasibility of diet mediterranisation, in a food-at-work context, and its consequence on metabolic syndrome in a mid-age unselected healthy male population group. One-year longitudinal intervention study. Physical exercise was not modified. All workers of the Santiago division of 'Maestranza Diesel', a metal-mechanic company servicing the mining industry, were invited to participate. Initially, 145 workers of a total of 171, of average age 39 years, accepted to participate (sixteen women and 129 men). A subgroup of ninety-six men fully completed the controls programmed for the intervention study. Losses from the original group correspond to missing one control (sixteen), leaving the company (eleven) or blood sampling discomfort (six). The women and sixteen male workers, hired post study initiation, did participate but were excluded from this 12-month analysis. Diet mediterranisation was successful, reflected in the daily food consumption at the canteen and the evolution of the Mediterranean diet score (MDS) from 4.8 +/- 1.4 to 7.4 +/- 1.5 (limits 0-14). Some metabolic syndrome components showed statistically significant improvement and also statistically significant correlation with the MDS: waist circumference, HDL-cholesterol, systolic and diastolic blood pressure. After 12 months, the reversion rate for metabolic syndrome was 48 % (12/23) with an incidence rate of 4.1 % for new cases (3/73). In total, metabolic syndrome decreased from 24.0 % to 15.6 % (23/96 to 15/96) (P = 0.029). Diet mediterranisation is feasible in a food-at-work intervention, affecting lunch consumption at the workers canteen and overall consumption evaluated with MDS, together with a significant reduction in metabolic syndrome.
    Public Health Nutrition 10/2009; 12(9A):1635-43. · 2.25 Impact Factor
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    World review of nutrition and dietetics 02/2008; 98:150-73.
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    ABSTRACT: Septic shock (SS)-related multiorgan dysfunction has been associated with oxidative damage, but little is known about the temporal damage profile and its relationship to severity. The present work investigated prospectively 21 SS patients. Blood samples were obtained at diagnosis, 24, 72 hours, day 7, and at 3 months. At admission, thiobarbituric acid reactive substances (TBARSs), plasma protein carbonyls, plasma protein methionine sulfoxide (MS), ferric/reducing antioxidant power (FRAP), total red blood cell glutathione (RBCG), uric acid (UA), and bilirrubin levels were increased (P < .05). Total radical-trapping antioxidant potential (TRAP) and vitamin-E were similar to controls, and vitamin-C was decreased (P < .05). During evolution, TBARS and RBCG increased (P < .001), vitamin-E levels remained stable, whereas plasma protein carbonyls and MS, TRAP, vitamin-C, reduced glutathione, and UA levels decreased (P < .006). After 3 months, plasma protein carbonyls and MS persisted elevated. More severe patients exhibited higher TBARS, TRAP, FRAP, vitamin-C, UA, and bilirrubin levels. Our results suggest early and persistent oxidative stress during septic shock and a correlation between increasing levels of lipoperoxidation and sepsis severity.
    Mediators of Inflammation 01/2008; 2008:168652. · 3.88 Impact Factor
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    ABSTRACT: The facilitative glucose transporter, GLUT4, mediates insulin-stimulated glucose uptake in adipocytes and muscles, and the participation of GLUT4 in the pathogenesis of various clinical conditions associated with obesity, visceral fat accumulation and insulin resistance has been proposed. Glucose uptake by some members of the GLUT family, mainly GLUT1, is inhibited by flavonoids, the natural polyphenols present in fruits, vegetables and wine. Therefore it is of interest to establish if these polyphenolic compounds present in the diet, known to be effective antioxidants but also endowed with several other biological activities such as protein-tyrosine kinase inhibition, interfere with GLUT4 function. In the present study, we show that three flavonoids, quercetin, myricetin and catechin-gallate, inhibit the uptake of methylglucose by adipocytes over the concentration range of 10-100 microM. These three flavonoids show a competitive pattern of inhibition, with K(i)=16, 33.5 and 90 microM respectively. In contrast, neither catechin nor gallic acid inhibit methylglucose uptake. To obtain a better understanding of the interaction among GLUT4 and flavonoids, we have derived a GLUT4 three-dimensional molecular comparative model, using structural co-ordinates from a GLUT3 comparative model and a mechanosensitive ion channel [PDB (Protein Data Bank) code 1MSL] solved by X-ray diffraction. On the whole, the experimental evidence and computer simulation data favour a transport inhibition mechanism in which flavonoids and GLUT4 interact directly, rather than by a mechanism related to protein-tyrosine kinase and insulin signalling inhibition. Furthermore, the results suggest that GLUT transporters are involved in flavonoid incorporation into cells.
    Biochemical Journal 04/2005; 386(Pt 3):471-8. · 4.65 Impact Factor
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    ABSTRACT: (1) To compare the effect of an alcohol-free Mediterranean-type diet (MD) and a high-fat diet (HFD) on variables of primary haemostasis (bleeding time, plasma von Willebrand factor and platelet aggregation/secretion). (2) To test whether red wine supplementation modified these variables, independently of the diet. DESIGN, SUBJECTS AND INTERVENTION: Controlled prospective intervention study. Two groups, each consisting of 21 healthy male university students (22+/-3.4 y), received either MD or HFD during 90 days. Between days 30 and 60, both diets were supplemented with 240 ml/day of red wine. Baseline (T0) and T30, T60 and T90-day samples were drawn. Bleeding time was measured before (day 30) and after (day 60) wine supplementation. No drop out from the study was experienced. University campus and outpatient nutrition clinic. All baseline (day 0) variables did not differ significantly between study groups. On day 30, individuals on MD had significantly higher levels of plasma beta-carotene, folate, ascorbate, and eicosapentaenoic acid in plasma lipid fractions, than those on HFD. Total plasma cholesterol, HDL and LDL did not change significantly in either study group at any time point. After 30 days on each diet, individuals on MD had longer bleeding time (BT) than those on HFD (7.6+/-2.8 vs 5.8+/-1.7 min; P=0.017). BT did not change significantly after I month of wine supplementation (7.1+/-2.0 vs 5.5+/-2.0 min, respectively). Plasma von Willebrand factor (vWF : Ag) on day 0 was 89+/-40 and 111+/-70% in MD and HFD groups, respectively (P=0.21). These values did not change significantly at 30, 60 or 90 days. MD intake was associated with an increase in platelet serotonin secretion (P=0.02) and a marginal increase in platelet aggregation after stimulation with epinephrine (P=0.07). Wine intake resulted in a marginal decrease in platelet (14)C-5-HT secretion with 4 micro M ADP (P=0.07). However, both platelet aggregation and secretion were consistently increased when using collagen as agonist (1 and 2 micro g/ml, P=0.01). The longer BT in individuals on MD, obtained independently of red wine, denotes less interaction of platelets with the vascular wall, which could be beneficial from the point of view of cardiovascular (CV) risk. This effect is not explained by changes in the measured haemostatic determinants of BT (plasma vWF, ex vivo platelet function), and might be attributed to other as yet unknown vascular factors. Moderate consumption of red wine results in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen. This observation contradicts previous reports, although further studies are required to elucidate the influence of this finding on CV risk.
    European Journal of Clinical Nutrition 04/2003; 57(3):439-46. · 2.76 Impact Factor
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    ABSTRACT: Oxidative stress is a central mechanism for the pathogenesis of ischemic heart disease and atherogenesis, for cancer and other chronic diseases in general, and it also plays a major role in the aging process. Dietary antioxidants constitute a large group of compounds that differ in mechanism of action, bioavailability and side effects. A systematic analysis of the role of the various antioxidants in chronic diseases is hampered by the difficulty of employing death or clinical events as end points in intervention studies. Therefore, valid markers for oxidative stress, which show dose response and are sensitive to changes in dietary supply of antioxidants, are potentially of great value when trying to establish healthy dietary patterns, or when one component, like red wine, is evaluated specifically. To evaluate potential oxidative stress markers we have studied the effect of different diets plus wine supplementation on antioxidant defenses and oxidative damage. In three experimental series, four groups of young male university students, one of older men and other of older women, 20-24 volunteers each, received Mediterranean or occidental (high-fat) diets alone or supplemented with red wine, white wine, or fruits and vegetables. Measurements included, leukocyte DNA 8-OH-deoxyguanosine (8OHdG), plasma 7 beta-hydroxycholesterol, TBARS and well-characterized antioxidants, and plasma and urine polyphenol antioxidants. In all experimental groups that received red wine, consumption resulted in marked decrease in 8OHdG. The changes observed in 8OHdG correlate positively with the other markers of oxidative damage, and shows a clear inverse correlation with the plasma level of well established antioxidants and with measurements of total antioxidant capacity. Urinary total polyphenol content as well as the sum of some specific plasma species also correlate inversely with 8OHdG. In conclusion, the results identify 8OHdG as a very promising general marker of oxidative stress in nutrition intervention studies in humans, and red wine shows a remarkable protective effect.
    Annals of the New York Academy of Sciences 06/2002; 957:136-45. · 4.38 Impact Factor
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    ABSTRACT: Despite the physiologic importance of vitamin E, in particular its alpha-tocopherol (alpha-T) isoform, the molecular mechanisms involved in the cellular uptake of this antioxidant from plasma lipoproteins have not been well-defined. Recent studies have suggested that selective lipid uptake, rather than endocytosis, is important for alpha-T delivery to cells. Here we show that the scavenger receptor class B type I (SR-BI), which mediates cellular selective cholesteryl ester uptake from lipoproteins, facilitates efficient transfer of alpha-T from HDL to cultured cells. In SR-BI-deficient mutant mice, relative to wild-type control animals, there was a significant increase in plasma alpha-T levels (1.1- to 1.4-fold higher) that was mostly due to the elevated alpha-T content of their abnormally large plasma HDL-like particles. This increase in plasma alpha-T in SR-BI knockout mice was accompanied by a significant decrease (65-80%) in the alpha-T concentrations in bile and several tissues including ovary, testis, lung and brain. SR-BI deficiency did not alter the alpha-T concentrations of the liver, spleen, kidney or white fat. These data show that SR-BI plays an important role in transferring alpha-T from plasma lipoproteins to specific tissues. Also, in the case of the liver as was previously shown for SR-BI-dependent hepatic cholesterol transport, SR-BI-mediated uptake of alpha-T was primarily coupled to biliary excretion rather than to tissue accumulation. Defective tissue uptake of lipoprotein alpha-T in SR-BI-deficient mice may contribute to the reproductive and cardiovascular pathologies exhibited by these animals.
    Journal of Nutrition 04/2002; 132(3):443-9. · 4.20 Impact Factor
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    ABSTRACT: Free radical-mediated oxidative damage is a known initial event in atherogenesis. Cardiovascular disease is frequent in the Chilean population showing differences in the prevalence of risk factors of the disease according to socioeconomic level (SEL). To determine levels of antioxidants and lipid peroxides in Chilean women from different SEL. Blood samples were taken from 81 women for measurements of plasma ascorbic acid, beta-carotene, alpha-tocopherol, licopene, ubiquinol, glutathione, total plasma antioxidant capacity, and lipid peroxides (TBARS). Individuals in the lower SEL showed reduced levels of plasma beta-carotene, ascorbic acid, alpha-tocopherol, and ubiquinol compared to women in the higher SEL. There were no differences between groups in the plasma levels of glutathione, total antioxidant capacity, or TBARS. The results could be explained in part by the higher consumption of fruits and vegetables in women from the upper SEL.
    Revista medica de Chile 02/2001; 129(1):43-50. · 0.36 Impact Factor
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    ABSTRACT: Hyperhomocysteinemia in association with vitamin B12 deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B12 normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 μg) in 18 individuals, serum vitamin B12 increased from 149±63 pg/mL to 532±204 pg/mL (p<0.0001) and total tHcy dropped from 12.4±4.7 to 7.9±3.1 μmol/L (p<0.0001). Ten of fourteen of these vegetarians completed an 8-week supplementation with 700 mg/day of each eicosapentaenoic and docosahexaenoic acids. Increased incorporation of these fatty acids into plasma lipids was observed in all of them, together with a significant reduction in maximum percentage or slope of platelet aggregation with all the agonists tested (ADP, epinephrin, collagen, arachidonic acid). No significant change in bleeding time was observed after n-3 fatty acid trial. Supplementation with vitamin B12 and n-3 fatty acids corrects hyperhomocysteinemia and reduces platelet reactivity to agonists in vegetarians. Whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated.
    Thrombosis Research 11/2000; · 3.13 Impact Factor
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    ABSTRACT: Hyperhomocysteinemia in association with vitamin B12 deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B12 normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 μg) in 18 individuals, serum vitamin B12 increased from 149±63 pg/mL to 532±204 pg/mL (p
    Thrombosis Research - THROMB RES. 01/2000; 100(3):153-160.
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    ABSTRACT: We studied hemostatic and inflammatory cardiovascular risk factors (CVRF), and total plasma homocysteine (tHcy) in 26 vegetarians (23 lacto- or ovolactovegetarians and 3 vegans), matched by age, sex and socioeconomic status with omnivorous controls. Vegetarians had significantly lower proportion of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma lipids, significantly shortened bleeding time, and increased blood platelet count and in vitro platelet function (aggregation and secretion). Plasma levels of all coagulation or fibrinolytic factors and natural inhibitors synthesized in the liver were lower in vegetarians than in controls. Whereas for some factors this decrease was statistically significant (fibrinogen, factor VIIc, antithrombin III, protein S, plasminogen) for the remaining (factors VIIIc, Vc, prothrombin, protein C) a trend in the same direction was found. For hemostatic proteins of predominantly extrahepatic origin (von Willebrand factor. tPA, PAI-1) this tendency was not present. No significant differences in inflammatory proteins (C-reactive protein and alpha1-protease inhibitor) were detected in both groups. tHcy was significantly increased in vegetarians, and correlated only with cobalamin levels. The increased platelet function and tHcy found in vegetarians may counteract the known cardiovascular health benefits of vegetarian diet (VD).
    Thrombosis and Haemostasis 07/1999; 81(6):913-7. · 6.09 Impact Factor
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    ABSTRACT: An intervention study was performed to evaluate the influence of a Mediterranean diet, a high fat diet, and their supplementation with red wine in moderate amounts, on biochemical, physiological, and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months two groups of 21 male volunteers each, received either a Mediterranean diet or a high fat diet; during the second month, red wine was added isocalorically, 240 ml/day. Participants were kept under close medical and nutritional surveillance. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. Plasma vitamin C was significantly decreased in the high fat diet group compared to the Mediterranean diet group. After wine supplementation to the Mediterranean diet, a significant 13.5% increase in plasma vitamin C was observed. Furthermore, when wine was added vitamin E decreased significantly in plasma, 15% in the high fat diet and 26% in the Mediterranean diet. Total plasma antioxidant capacity (total antioxidant reactivity) increased 28% above basal levels in the Mediterranean diet group, but not in the high fat diet group. In both groups, wine induced a marked increase in total antioxidant reactivity above basal levels, 56% and 23%, respectively. Oxidative DNA damage, detected as 8-hydroxydeoxyguanosine (8-OHdG) levels in blood leukocyte DNA, was markedly increased by the high fat diet; however, it was strongly reduced, to approximately 50% basal values, after wine supplementation, both in the high fat diet and Mediterranean diet groups. Endothelial function, evaluated noninvasively as flow-mediated vascular reactivity of the brachial artery, was suppressed by the high fat diet, and was normal after wine supplementation. These effects are attributed to oxidative stress associated with a high fat diet, and to the elevated plasma antioxidant capacity associated with wine consumption and the Mediterranean diet. The results presented support the following conclusions: a high fat diet induces oxidative stress; a diet rich in fruits and vegetables enhances antioxidant defenses; wine supplementation to a high fat or a Mediterranean diet increases plasma antioxidant capacity, decreases oxidative DNA damage, and normalizes endothelial function.
    Drugs under experimental and clinical research 02/1999; 25(2-3):133-41.