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Effects of dietary fiber intake on risk factors for cardiovascular disease in subjects at high risk

  • Estruch, Ramón
  • Martínez-González, Miguel Ángel
  • Corella, Dolores
  • Basora, Josep
  • Ruiz-Gutiérrez, Valentina
  • Covas, María-Isabel
  • Fiol, Miquel
  • Gómez-Gracia, Enrique
  • López-Sabater, M. C.
  • Escoda, R.
  • Pena, M. A.
  • Díez-Espino, Javier
  • Lahoz, C.
  • Lapetra, José
  • Sáez, Guillermo T.
  • Ros Ibarra, Eduardo
Background: Epidemiological studies and feeding trials with supplements suggest that fibre intake is associated with a reduction in cardiovascular risk. However, the effects of changes in dietary fibre on risk factor levels have not been evaluated in free-living individuals. Thus, the effects of changes in dietary fibre intake on cardiovascular risk factors were assessed over 3 months in free-living high-risk subjects. Methods: 772 high-risk subjects (age 69±5 years) were assigned to a low-fat diet or two Mediterranean-style diets. All participants received behavioural and nutritional education, including recommendations for increasing the consumption of vegetables, fruits, and legumes. Changes in food and nutrient intake, body weight, blood pressure, lipid profiles, glucose control and inflammatory markers were evaluated. Results: Most participants increased consumption of vegetable products, but the increase in dietary fibre exhibited wide between-subject variability (6–65 g/day). Body weight, waist circumference, and mean systolic and diastolic blood pressure decreased across quintiles of fibre intake (p<0.005; all). Reductions in fasting glucose and total cholesterol levels, and increments in HDL cholesterol were highest among participants in the upper 20% of fibre intake (p = 0.04 and 0.02 respectively). Plasma concentrations of C-reactive protein, but not those of inflammatory cytokines, decreased in parallel with increasing dietary fibre (p = 0.04). Significant reductions in LDL cholesterol were observed only among participants with the greatest increases in soluble fibre intake (p = 0.04). Conclusions: Increasing dietary fibre intake with natural foods is associated with reductions in classical and novel cardiovascular risk factors in a high-risk cohort., Corella Piquer, Maria Dolores, Dolores.Corella@uv.es

Cooperative thermal and optical switching of spin states in a new two-dimensional coordination polymer

  • Niel, Virginie
  • Galet, Ana
  • Gaspar Pedrós, Ana Belén
  • Muñoz, M. Carmen
  • Real Cabezos, José Antonio
{Fe(pmd)2[Cu(CN)2]2} (pmd = pyrimidine) displays a rigid two-dimensional structure and undergoes thermal- and optical-driven spin crossover behaviour; cooperative elastic coupling between iron(II) ions in the framework induces thermal hysteresis in the HS↔LS conversion and sigmoidal HS→LS relaxation of the photo-induced HS state at low temperatures., Niel, Virginie, Virginie.Niel@uv.es ; Galet Domingo, Ana Guadalupe, Ana.Galet@uv.es ; Gaspar Pedros, Ana Belen, Ana.B.Gaspar@uv.es ; Real Cabezos, Jose Antonio, Jose.A.Real@uv.es

Separating the Mechanism-Based and Off-Target Actions of Cholesteryl Ester Transfer Protein Inhibitors With CETP Gene Polymorphisms

  • Sofat, Reecha
  • Hingorani, Aroon D.
  • Smeeth, Liam
  • Humphries, Steve E.
  • Talmud, Philippa J.
  • Cooper, Jackie
  • Shah, Tina
  • Sandhu, Manjinder S.
  • Ricketts, Sally L.
  • Boekholdt, S. Matthijs
  • Wareham, Nicholas
  • Khaw, Kay Tee
  • Kumari, Meena
  • Kivimaki, Mika
  • Marmot, Michael
  • Asselbergs, Folkert W.
  • van der Harst, Pim
  • Dullaart, Robin P.F.
  • Navis, Gerjan
  • van Veldhuisen, Dirk J.
  • Van Gilst, Wiek H.
  • Thompson, John F.
  • McCaskie, Pamela
  • Palmer, Lyle J.
  • Arca, Marcello
  • Quagliarini, Fabiana
  • Gaudio, Carlo
  • Cambien, François
  • Nicaud, Viviane
  • Poirer, Odette
  • Gudnason, Vilmundur
  • Isaacs, Aaron
  • Witteman, Jacqueline C.M.
  • van Duijn, Cornelia M.
  • Pencina, Michael
  • Vasan, Ramachandran S.
  • D'Agostino, Ralph B.
  • Ordovas, Jose M.
  • Li, Tricia Y.
  • Kakko, Sakari
  • Kauma, Heikki
  • Savolainen, Markku J.
  • Kesäniemi, Antero
  • Sandhofer, Anton
  • Paulweber, Bernhard
  • Sorlí Guerola, José Vicente
  • Goto, Akimoto
  • Yokoyama, Shinji
  • Okumura, Kenji
  • Horne, Benjamin D.
  • Packard, Chris
  • Freeman, Dilys
  • Ford, Ian
  • Sattar, Naveed
  • McCormack, Valerie
  • Lawlor, Debbie A.
  • Ebrahim, Shah
  • Smith, George Davey
  • Kastelein, John J.P.
  • Deanfield, John
  • Casas, Juan P.
Background— Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target. Methods and Results— We compared the effect of CETP single-nucleotide polymorphisms and torcetrapib treatment on lipid fractions, blood pressure, and electrolytes in up to 67 687 individuals from genetic studies and 17 911 from randomized trials. CETP single-nucleotide polymorphisms and torcetrapib treatment reduced CETP activity and had a directionally concordant effect on 8 lipid and lipoprotein traits (total, low-density lipoprotein, and HDL cholesterol; HDL2; HDL3; apolipoproteins A-I and B; and triglycerides), with the genetic effect on HDL cholesterol (0.13 mmol/L, 95% confidence interval [CI] 0.11 to 0.14 mmol/L) being consistent with that expected of a 10-mg dose of torcetrapib (0.13 mmol/L, 95% CI 0.10 to 0.15). In trials, 60 mg of torcetrapib elevated systolic and diastolic blood pressure by 4.47 mm Hg (95% CI 4.10 to 4.84 mm Hg) and 2.08 mm Hg (95% CI 1.84 to 2.31 mm Hg), respectively. However, the effect of CETP single-nucleotide polymorphisms on systolic blood pressure (0.16 mm Hg, 95% CI –0.28 to 0.60 mm Hg) and diastolic blood pressure (–0.04 mm Hg, 95% CI –0.36 to 0.28 mm Hg) was null and significantly different from that expected of 10 mg of torcetrapib. Conclusions— Discordance in the effects of CETP single-nucleotide polymorphisms and torcetrapib treatment on blood pressure despite the concordant effects on lipids indicates the hypertensive action of torcetrapib is unlikely to be due to CETP inhibition or shared by chemically dissimilar CETP inhibitors. Genetic studies could find a place in drug-development programs as a new source of randomized evidence for drug-target validation in humans., Sorli Guerola, Jose Vicente, Jose.Sorli@uv.es

Dietary Intake of n-6 Fatty Acids Modulates Effect of Apolipoprotein A5 Gene on Plasma Fasting Triglycerides, Remnant Lipoprotein Concentrations, and Lipoprotein Particle Size

  • Lai, Chao-Qiang
  • Corella, Dolores
  • Demissie, Serkalem
  • Cupples, L. Adrienne
  • Adiconis, Xian
  • Yueping, Zhu
  • Parnell, Laurence D.
  • Tucker, Katherine L.
  • Ordovas, Jose M.
Background— Apolipoprotein A5 gene (APOA5) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association. Methods and Results— We investigated the interaction between APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant-like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and 1147 women who were Framingham Heart Study participants. Polymorphisms –1131T>C and 56C>G, representing 2 independent haplotypes, were analyzed. Significant gene–diet interactions between the –1131T>C polymorphism and polyunsaturated fatty acid (PUFA) intake were found (P<0.001) in determining fasting TGs, RLP concentrations, and particle size, but these interactions were not found for the 56C>G polymorphism. The –1131C allele was associated with higher fasting TGs and RLP concentrations (P<0.01) in only the subjects consuming a high-PUFA diet (>6% of total energy). No heterogeneity by sex was found. These interactions showed a dose-response effect when PUFA intake was considered as a continuous variable (P<0.01). Similar interactions were found for the sizes of VLDL and LDL particles. Only in carriers of the –1131C allele did the size of these particles increase (VLDL) or decrease (LDL) as PUFA intake increased (P<0.01). We further analyzed the effects of n-6 and n-3 fatty acids and found that the PUFA–APOA5 interactions were specific for dietary n-6 fatty acids. Conclusions— Higher n-6 (but not n-3) PUFA intake increased fasting TGs, RLP concentrations, and VLDL size and decreased LDL size in APOA5 –1131C carriers, suggesting that n-6 PUFA–rich diets are related to a more atherogenic lipid profile in these subjects., Corella Piquer, Maria Dolores, Dolores.Corella@uv.es

Discrepancies Between Nitroglycerin and NO-Releasing Drugs on Mitochondrial Oxygen Consumption, Vasoactivity, and the Release of NO

  • Nuñez, Cristina
  • Víctor González, Víctor Manuel
  • Tur, Remedios
  • Alvarez Barrientos, Alberto
  • Moncada, Salvador
  • Esplugues Mota, Juan Vicente
  • D'Ocon Navaza, Pilar
It has been generally acknowledged that the actions of glyceryl trinitrate (GTN) are a result of its bioconversion into NO. However, recent observations have thrown this idea into doubt, with many studies demonstrating that NO is present only when there are high concentrations of GTN. We have explored this discrepancy by developing a new approach that uses confocal microscopy to directly detect NO. Intracellular levels of NO in the rat aortic vascular wall have been compared with those present after incubation with 3 different NO donors (DETA-NO, 3 morpholinosydnonimine, and S-nitroso-N-acetylpenicillamine), endothelial activation with acetylcholine, or administration of GTN. We have also evaluated the relaxant effects of these treatments on isolated rings of aorta following activation of the enzyme soluble guanylyl cyclase and their inhibitory action on mitochondrial respiration, which is an index of the interaction of NO with the enzyme of the electron transport chain cytochrome C oxidase. In the case of the various NO donors and acetylcholine, we detected a concentration-dependent relationship in the intensity of vascular relaxation and degree of NO fluorescence and an increase in the Michaelis constant (Km) for O2. GTN did not produce similar effects, and although clinically relevant concentrations of this compound caused clear, concentration-related relaxations, there was neither any increase in NO-related fluorescence nor an augmented Km for O2. The nature of these differences suggests that these concentrations of GTN do not release free NO but probably a different species that, although it interacts with soluble guanylyl cyclase in vascular smooth muscle, does not inhibit O2 consumption by vascular mitochondria., Victor Gonzalez, Victor Manuel, Victor.Victor@uv.es ; Esplugues Mota, Juan Vicente, Juan.V.Esplugues@uv.es ; d'Ocon Navaza, Maria Pilar, M.Pilar.Docon@uv.es

Are epizoites biological indicators of a western Mediterranean striped dolphin die-off?

  • Aznar Avendaño, Francisco Javier
  • Balbuena, Juan Antonio
  • Raga Esteve, Juan Antonio
During a die-off of Mediterranean striped dolphins Stenella coeruleoalba in 1990-91, 82 individuals stranded on the Spanish coast were examined for crustacean ectoparasites and epizoites. Six species were detected: Syncyarnus aequus, PenneUa sp., Xenobalanus globicipitis, Conchoderma virgatum, Lepas pectinata and Lepas cf. hillii. The barnacles L. pectinata and L. cf. hillii are reported here for the first time on cetaceans; they were attached to the teeth. C. virgaturn was also found on the teeth; this is an unusual attachment on cetaceans. X. globicipitis showed a higher prevalence on the dolphins studied than on those stranded in the same months before (1980 to 1990) and after (1991 to 1993) the epizootic. An analysis of shell and pseudocapitulum sizes of the X. globicipitis infrapopulations indicated possible recent colonization. It is suggested that settlement of some epizoites might have increased due to reduced movement of the dolphins and/or impaired regenerative and immune functioning of the skin prior to death. This might account for the exceptional occurrence of Lepas spp. attached on the teeth, the unusual attachment of C. virgatum, and the higher prevalence and apparently young infrapopulations of X. globicipitis., Aznar Avendano Francisco Javier Francisco.Aznar@uv.es Balbuena Diaz-Pines, Juan Antonio, J.A.Balbuena@uv.es ; Raga Esteve, Juan Antonio, Toni.Raga@uv.es

Birth weight impacts on wave reflections in children and adolescents

  • Lurbe i Ferrer, Empar
  • Torró Doménech, María Isabel
  • Carvajal Roca, María Eva
  • Alvarez, Vicente
  • Redón i Más, Josep
The objective of the present study was to assess central aortic pressure and wave reflection in children and adolescents at different birth weights. Two hundred nineteen healthy children (126 girls), from 7 to 18 years of age (mean, 11.3 years) and born at term after a normotensive pregnancy, were included. The subjects were divided according to birth weight: <2.5 kg, from 2.5 to 2.999 kg, from 3.0 to 3.5 kg, and >3.5 kg. Pressure waveforms were recorded from the radial artery of the wrist, and the waveform data were then processed by the SphygmoCor radial/aortic transform software module to produce the estimated aortic pressure waveform. Augmentation index, an estimate of the pulse wave reflection, was significantly higher in children with the lowest birth weights compared with the other birth weight groups. In a multiple regression analysis, short stature, low heart rate, female gender, and lower birth weight had independent significant inverse correlations to the augmentation index when adjusted for diastolic blood pressure (R^2=0.21). In summary, the results showed a relatively aged phenotype of large-vessel function in the children with the lowest birth weights. These early alterations may be amplified throughout life and may contribute to the increased cardiovascular risk associated with low birth weight., Lurbe Ferrer, Maria Desamparados, Empar.Lurbe@uv.es ; Redon Mas, Josep, Josep.Redon@uv.es

A review of virus infections of cetaceans and the potential impact of morbilliviruses, poxviruses and papillomaviruses on host population dynamics

  • Van Bressem, Marie-Françoise
  • Van Waerebeek, Koen
  • Raga Esteve, Juan Antonio
Viruses belonging to 9 families have been detected in cetaceans. We critically review the clinical features, pathology and epidemiology of the diseases they cause. Cetacean morbillivirus (family Paramyxoviridae) induces a serious disease with a high mortality rate and persists in several populations. It may have long-term effects on the dynamics of cetacean populations either as enzootic infection or recurrent epizootics. The latter presumably have the more profound impact due to removal of sexually mature individuals. Members of the family Poxviridae infect several species of odontocetes, resulting in ring and tattoo skin lesions. Although poxviruses apparently do not induce a high mortality, circumstancial evidence suggests they may be lethal in young animals lacking protective immunity, and thus may negatively affect net recruitment. Papillomaviruses (family Papovaviridae) cause genital warts in at least 3 species of cetaceans. In 10% of male Burmeister's porpoises Phocoena spinipinnis from Peru, lesions were sufficiently severe to at least hamper, if not impede, copulation. Members of the families Herpesviridae, Orthomyxoviridae and Rhabdoviridae were demonstrated in cetaceans suffering serious illnesses, but with the exception of a 'porpoise herpesvirus' their causative role is still tentative. Herpes-like viruses and caliciviruses (Caliciviridae) give rise to cutaneous diseases in Monodontidae and Delphinidae. Antibodies to several serotypes of caliciviruses were found in odontocetes and mysticetes. An unrecognized Hepadnaviridae was detected by serology in a captive Pacific white-sided dolphin Lagenorhynchus obliquidens with chronic persistent hepatitis. Adenoviruses (Adenoviridae) were isolated from the intestinal tracts of mysticeti and a beluga Delphinapterus leucas but were not associated with any pathologies. We discuss the potential impact of Paramyxoviridae, Poxviridae and Papovaviridae on the dynamics of several odontocete populations., Raga Esteve, Juan Antonio, Toni.Raga@uv.es

Effectiveness of different vaccine formulations against vibriosis caused by Vibrio vulnificus serovar E (biotype 2) in European eels Anguilla anguilla

  • Collado Nieto, Rosa María
  • Fouz Rodríguez, Belén
  • Sanjuán Caro, Eva
  • Amaro González, Carmen
Vibriosis due to Vibrio vulnificus serovar E (biotype 2) is one of the main causes of mortality in European eels cultured in Europe. The main objective of this study was to develop a vaccine and a vaccination procedure against this pathogen. With this aim, we tested several vaccine formulations (inactivated whole-cells with and without toxoids‹inactivated extracellular products‹from capsulated and uncapsulated strains, attenuated live vaccines and purified lipopolysaccharide [LPS]) on eels maintained under controlled laboratory conditions using different delivery routes (injection and immersion). To study the immune response we estimated antibody titers and bactericidal/bacteriostatic activity in mucus and serum. To evaluate protection, we calculated the relative percent survival (RPS) after intraperitoneal (i.p.) injection and bath challenge of the pathogen. The overall results indicate that: (1) capsular antigens seem to be essential for protective immunization; (2) vaccines confer the highest protection when administered by i.p. injection; (3) booster is needed to achieve good protection by immersion; (4) enriching the vaccine with toxoids enhances protection to optimal levels (RPS values around 70 to 100%, depending on the delivery route); and (5) the protective effect in serum and mucus depends on the route of administration and seems to be related to the production of specific antibodies., Fouz Rodriguez, Belen, Belen.Fouz@uv.es ; Sanjuan Caro, Eva, Eva.Sanjuan@uv.es ; Amaro Gonzalez, Carmen, Carmen.Amaro@uv.es

Field testing of a vaccine against eel diseases caused by Vibrio vulnificus

  • Fouz Rodríguez, Belén
  • Esteve Gassent, María Dolores
  • Barrera, Rodolfo
  • Larsen, Jens Laurits
  • Nielsen, Michael Engelbrecht
  • Amaro González, Carmen
The field results of a vaccination programme against Vibrio vulnificus serovar E (biotype 2) in a Spanish eel farm are reported. A total of 9.5 million glass eels were vaccinated from January 1998 to March 2000 by prolonged immersion followed by 2 subsequent reimmunisations after 12 to 14 and 24 to 28 d, respectively. The acquired protection and the immune response against serovar E were estimated over a period of 6 mo after vaccination. A similar vaccination schedule was conducted with elvers in a Danish eel farm. In this case, the acquired protection and the immune response against serovar E and the new eel-pathogenic serovars, recently described in Denmark, were evaluated over a short term. The overall results show that the vaccine against V. vulnificus serovar E induces a satisfactory protective immunity during the main growth period of eels (around 6 mo) with a relative percentage survival of 62 to 86% and protects them against the new eel-pathogenic serovars. Vaccination of eels by immersion seems to be the best strategy to prevent diseases caused by V. vulnificus., Fouz Rodriguez, Belen, Belen.Fouz@uv.es ; Amaro Gonzalez, Carmen, Carmen.Amaro@uv.es

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