Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: a randomized pilot study.

BackgroundOmega-3 fatty acids prevent cardiovascular disease (CVD) events in patients with myocardial infarction or heart failure. Benefits in patients without overt CVD have not been demonstrated, though most studies did not use treatment doses (3.36 g) of omega-3 fatty acids. Arterial stiffness measured by pulse wave velocity (PWV) predicts CVD events independent of standard risk factors. However, no therapy has been shown to reduce PWV in a blood pressure-independent manner. We assessed the effects of esterified omega-3 fatty acids on PWV and serum markers of inflammation among patients with hypertension.Design and methodsWe performed a prospective, randomized; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban, safety net hospital. Patients received 3.36 g of omega-3 fatty acids vs. matched placebo daily for 3-months. The principal outcome measure was change in brachial-ankle PWV. Serum inflammatory markers associated with CVD risk were also assessed.ResultsThe majority (71 %) were of Latino ethnicity. After 3-months, mean change in arterial PWV among omega-3 and placebo groups was -97 cm/s vs. -33 cm/s respectively (p = 0.36 for difference, after multivariate adjustment for baseline age, systolic blood pressure, and serum adiponectin). Non-significant reductions in lipoprotein-associated phospholipase A2 (LpPLA2) mass and high sensitivity C-reactive protein (hsCRP) relative to placebo were also observed (p = 0.08, and 0.21, respectively).ConclusionHigh-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension.Clinical trial registrationNCT00935766 , registered July 8 2009

Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults.

Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA) compared to non-Latino whites (NLW). Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.). We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue), insulin sensitivity (IVGTT), and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003), and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R² = 0.42, p < 0.01). Lower adiponectin was also associated with higher dietary glycemic index, lower intake of vegetables, higher intake of trans fat, and higher intake of grains. Our findings confirm that ethnic differences in adiponectin reflect differences in insulin sensitivity, but suggest that these are not due to differences in adiposity. Observed associations between adiponectin and diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors

Serverification of Molecular Modeling Applications: the Rosetta Online Server that Includes Everyone (ROSIE)

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org

Production and characterization of micro-size pores for ion track etching applications

For many years the applications of ion track etch materials have increased considerably, like charged particles detection, molecular identification with nanopores, ion track filters, magnetic studies with nanowires and so on. Over the materials generally used as track detector, the Poly-Allyl-Diglycol Carbonate (PADC), offers many advantages, like its nearly 100 % detection efficiency for charged particle, a high resistance to harsh environment, the lowest detection threshold, a high abrasion resistance and a low production costs. All of these properties have made it particularly attractive material, even if due to its brittleness, obtaining a thin film (less than 500 μm) is still a challenge. In this work, PADC foils have been exposed to a-particles emitted by a thin radioactive source of 241Am and to C ions from the Tandetron 4130 MC accelerator. The latent tracks generated in the polymer have been developed using a standard etching procedure in 6.25 NaOH solution. The dependence of the ion tracks' geometry on the ion beam energy and fluence has been evaluated combining the information obtained through a semiautomatic computer script that selects the etched ion tracks according to their diameter and mean grey value and nanometric resolution images by atomic force microscopy

Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure

AbstractOBJECTIVESThe primary purpose of this study was to determine the acute and long-term hemodynamic and clinical effects of irbesartan in patients with heart failure.BACKGROUNDInhibition of angiotensin II production by angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients with heart failure. Irbesartan is an orally active antagonist of the angiotensin II AT1receptor subtype with potential efficacy in heart failure.METHODSTwo hundred eighteen patients with symptomatic heart failure (New York Heart Association [NYHA] class II–IV) and left ventricular ejection fraction ≤40% participated in the study. Serial hemodynamic measurements were made over 24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study medication, patients receiving placebo were reallocated to one of the four irbesartan doses, treatment was continued for 12 weeks and hemodynamic measurements were repeated.RESULTSIrbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change −5.9 ± 0.9 mm Hg and −5.3 ± 0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine. The neurohormonal effects of irbesartan were highly variable and none of the changes was statistically significant. There was a significant dose-related decrease in the percentage of patients discontinuing study medication because of worsening heart failure. Irbesartan was well tolerated without evidence of dose-related cough or azotemia.CONCLUSIONSIrbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained hemodynamic improvement and prevented worsening heart failure

Pulse wave velocity and carotid atherosclerosis in White and Latino patients with hypertension

<p>Abstract</p> <p>Background</p> <p>Preventive cardiology has expanded beyond coronary heart disease towards prevention of a broader spectrum of cardiovascular diseases. Ethnic minorities are at proportionately greater risk for developing extracoronary vascular disease including heart failure and cerebrovascular disease.</p> <p>Methods</p> <p>We performed a cross sectional study of Latino and White hypertension patients in a safety-net healthcare system. Framingham risk factors, markers of inflammation (hsCRP, LPpLA2), arterial stiffness (Pulse wave velocity, augmentation index, and central aortic pressure), and endothelial function (brachial artery flow-mediated dilatation) were measured. Univariate and multivariable associations between these parameters and an index of extracoronary atherosclerosis (carotid intima media thickness) was performed.</p> <p>Results</p> <p>Among 177 subjects, mean age was 62 years, 67% were female, and 67% were Latino. In univariate analysis, markers associated with carotid intima media thickness (IMT) at p < 0.25 included pulse wave velocity (PWV), augmentation index (AIx), central aortic pressure (cAP), and LpPLA₂activity rank. However, AIx, cAP, and LpPLA2 activity were not significantly associated with carotid IMT after adjusting for Framingham risk factors (all p > .10). Only PWV retained a significant association with carotid IMT independent of the Framingham general risk profile parameters (p = .016). No statistically significant interactions between Framingham and other independent variables with ethnicity (all p > .05) were observed.</p> <p>Conclusion</p> <p>In this safety net cohort, PWV is a potentially useful adjunctive atherosclerotic risk marker independent of traditional risk factors and irrespective of ethnicity.</p