Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering

AbstractObjectivesThis study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia.BackgroundSimvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown.MethodsPigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated.ResultsTotal and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05).ConclusionsThese findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering

Building an end user focused THz based ultra high bandwidth wireless access network: The TERAPOD approach

The TERAPOD project aims to investigate and demonstrate the feasibility of ultra high bandwidth wireless access networks operating in the Terahertz (THz) band. The proposed TERAPOD THz communication system will be developed, driven by end user usage scenario requirements and will be demonstrated within a first adopter operational setting of a Data Centre. In this article, we define the full communications stack approach that will be taken in TERAPOD, highlighting the specific challenges and aimed innovations that are targeted

Endothelin-1 receptor blockade prevents renal injury in experimental hypercholesterolemia

Endothelin-1 receptor blockade prevents renal injury in experimental hypercholesterolemia.BackgroundThe potent vasoconstrictor endothelin-1 is involved in regulation of renal function, and is up-regulated in hypercholesterolemia (HC), a risk factor for renal disease that increases oxidative stress and impairs renal hemodynamic responses. However, the involvement of endothelin (ET) in this disease process is yet unknown.MethodsRegional renal hemodynamics and function in vivo were quantified in pigs at baseline and during infusion of acetylcholine using electron beam computed tomography after a 12-week normal diet (N = 6), HC diet (N = 6), and HC diet orally supplemented (4mg/kg/day) with the selective ET receptor-A (ET-A) blocker ABT-627 (HC+ET-A, N = 6). Plasma levels of 8-epi-PGF2-α-isoprostanes, markers of oxidative stress, were measured using enzyme immunoassay, and renal tissue was studied ex vivo using Western blotting, electrophoretic mobility shift assay, and immunohistochemistry.ResultsTotal and low-density lipoprotein (LDL) cholesterol were similarly increased, but isoprostanes were decreased in HC+ET-A compared to HC alone. Basal renal perfusion was similar among the groups, while glomerular filtration rate (GFR) increased in HC+ET-A compared to HC. Stimulated perfusion and GFR were blunted in HC, but normalized in HC+ET-A. Moreover, ET blockade increased expression of endothelial nitric oxide synthase, and decreased endothelial expression of the oxidized-LDL receptor LOX-1, as well as tubular immunoreactivity of inducible nitric oxide synthase, nitrotyrosine, nuclear factor-κB, transforming growth factor-β, and tubulointerstitial and perivascular trichrome staining.ConclusionET-A blockade improves renal hemodynamic and function in HC, and decreases oxidative stress, and renal vascular and tubulointerstitial inflammation and fibrosis. These findings support a role for the endogenous ET system in renal injury in HC and atherosclerosis

Misfolded α-Synuclein in Autosomal Dominant Alzheimer's Disease.

We analyzed Lewy body (LB) pathology in 18 autosomal dominant Alzheimer's disease (ADAD) brains via immunohistochemistry. Real-time quaking induced conversion was used to detect misfolded α-synuclein (α-syn) in 18 living ADAD cerebrospinal fluid (CSF) samples. Concomitant LB pathology was present in 44% ADAD brains. Only 6% CSF samples were positive for misfolded α-syn. In an additional AD sample, all patients with confirmed LB presented misfolded α-syn in postmortem CSF regardless of the LB staging. In conclusion, misfolded α-syn in CSF was scarce in symptomatic living ADAD individuals, in contrast to postmortem brain tissue. These results suggest late appearance of LB pathology in ADAD

El papel de la investigación para identificar oportunidades de mejora del regadío en Mauritania

Ponencia presentada en el I Congreso en Investigación en Agricultura para el desarrollo, celebrado en Madrid el 17 y 18 de octubre de 2011.-- Gómez Macpherson, H. et. al.La producción agrícola de Mauritania se concentra en el valle del río Senegal donde también se concentra gran parte de la población. Sólo un 0,5 % de la superficie mauritana es cultivable, y la tradicional dependencia de la agricultura pluvial ha provocado una alta inseguridad alimentaria; algo que quedó patente con las hambrunas causadas por los ciclos de sequía de los años 70. Los estados ribereños del río Senegal se organizaron entonces para desarrollar zonas regables con el objetivo de la seguridad alimentaria. En Mauritania, el regadío se orientó de forma exclusiva al cultivo del arroz, prácticamente desconocido en la zona. La ricicultura convive con sistemas tradicionales (pluviales y basados en el ciclo anual de inundación-recesión del río), pero el regadío es el sistema que garantiza la producción año a año. Sorprende por tanto que dos tercios de la superficie inicialmente regada se hayan abandonado. Esta paradoja fue el origen de la colaboración entre el Ministerio de Desarrollo Rural de Mauritania, el Instituto de Agricultura Sostenible y la Universidad Politécnica de Cataluña, concretada en proyectos financiados por AECID, y que tiene como objetivo ahondar en las razones del abandono del regadío y en buscar fórmulas para atajarlo. La colaboración se ha realizado sobre tres ejes principales: 1) comprender la interacción del regadío con los sistemas tradicionales de secano y de recesión de inundaciones; 2) diagnosticar el funcionamiento de los pequeños perímetros de riego; y 3) evaluar cultivos alternativos al arroz en términos de productividad de la tierra y del agua. Entre los cultivos regados de interés potencial se identificó el sorgo por ser del gusto de los habitantes del valle y cultivarse tradicionalmente en secano y tras la recesión del agua en suelos inundados.Los autores agradecen a los técnicos de campo y agricultores mauritanos por el trabajo realizado y al MDR y AECID por la financiación.Peer Reviewe

The Milky Way: An Exceptionally Quiet Galaxy; Implications for the formation of spiral galaxies

[Abridged]We compare both the Milky Way and M31 galaxies to local external disk galaxies within the same mass range, using their relative locations in the planes formed by V_flat versus M_K, j_disk, and the average Fe abundance of stars in the galaxy outskirts. We find, for all relationships, that the MW is systematically offset by ~ 1 sigma, showing a significant deficiency in stellar mass, in angular momentum, in disk radius and [Fe/H] in the stars in its outskirts at a given V_flat. On the basis of their location in the M_K, V_flat, and R_d volume, the fraction of spirals like the MW is 7+/-1%, while M31 appears to be a "typical'' spiral. Our Galaxy appears to have escaped any significant merger over the last ~10 Gyrs which may explain why it is deficient by a factor 2 to 3 in stellar mass, angular momentum and outskirts metallicity and then, unrepresentative of the typical spiral. As with M31, most local spirals show evidence for a history shaped mainly by relatively recent merging. We conclude that the standard scenario of secular evolution is generally unable to reproduce the properties of most (if not all) spiral galaxies. However, the so-called "spiral rebuilding'' scenario proposed by Hammer et al. 2005 is consistent with the properties of both distant galaxies and of their descendants - the local spirals.Comment: 14 pages, 6 figures, to appear in Ap

Highly Accurate Diagnosis of Pleural Tuberculosis by Immunological Analysis of the Pleural Effusion

Pleural TB is notoriously difficult to diagnose due to its paucibacillary nature yet it is the most common cause of pleural effusions in TB endemic countries such as The Gambia. We identified both cellular and soluble biomarkers in the pleural fluid that allowed highly accurate diagnosis of pleural TB compared to peripheral blood markers. Multi-plex cytokine analysis on unstimulated pleural fluid showed that IP-10 resulted in a positive likelihood ratio (LR) of 9.6 versus 2.8 for IFN-γ; a combination of IP-10, IL-6 and IL-10 resulted in an AUC of 0.96 and positive LR of 10. A striking finding was the significantly higher proportion of PPD-specific IFN-γ+TNF-α+ cell population (PPD-IGTA) in the pleural fluid compared to peripheral blood of TB subjects. Presence of this pleural PPD-IGTA population resulted in 95% correct classification of pleural TB disease with a sensitivity of 95% and specificity of 100%. These data suggest that analysis of the site of infection provides superior diagnostic accuracy compared to peripheral blood for pleural TB, likely due to the sequestration of effector cells at this acute stage of disease