Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of atherosclerotic plaque

Interest in the use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of three differently sized gadolinium-based contrast agents to permeate different mouse plaque phenotypes was evaluated with MRI. A tapered cast was implanted around the right carotid artery of apoE-/- mice to induce two different plaque phenotypes: a thin cap fibroatheroma (TCFA) and a non-TCFA lesion. Both plaques were allowed to develop over 6 and 9 weeks, leading to an intermediate and advanced lesion, respectively. Signal enhancement in the carotid artery wall, following intravenous injection of Gd-HP-DO3A as well as paramagnetic micelles and liposomes was evaluated. In vivo T1-weighted MRI plaque enhancement characteristics were complemented by fluorescence microscopy and correlated to lesion phenotype. The two smallest contrast agents, i.e. Gd-HP-DO3A and micelles, were found to enhance contrast in T1-weighted MR images of all investigated plaque phenotypes. Maximum contrast enhancement ranged between 53 and 70% at 6¿min after injection of Gd-HP-DO3A with highest enhancement and longest retention in the non-TCFA lesion. Twenty-four hours after injection of micelles maximum contrast enhancement ranged between 24 and 35% in all plaque phenotypes. Administration of the larger liposomes did not cause significant contrast enhancement in the atherosclerotic plaques. Confocal fluorescence microscopy confirmed the MRI-based differences in plaque permeation between micelles and liposomes. Plaque permeation of contrast agents was strongly dependent on size. Our results implicate that, when equipped with targeting ligands, liposomes are most suitable for the imaging of plaque-associated endothelial markers due to low background enhancement, whereas micelles, which accumulate extravascularly on a long timescale, are suited for imaging of less abundant markers inside plaques. Low molecular weight compounds may be employed for target-specific imaging of highly abundant extravascular plaque-associated target

Mechanical tension in the median nerve: The effects of joint positions

Stretch tests are attractive in the diagnosis of nerve root or peripheral nerve lesion. Interpretation of the test results is often difficult since the distribution of tensile forces along the nerve caused by the test manoeuvre is not known. In this study the effect on median nerve tension of 22 positions of the arm was measured with ‘buckle’ force transducers. With the elbow in full extension and the hand in neutral position, altering the position of the shoulder significantly influenced tension in the proximal part of the median nerve; tension in the distal part was not influenced. With the shoulder in 90 ° abduction, dorsiflexion of the hand combined with an extended elbow resulted in an increased tension in both distal and proximal parts of the median nerve. Dorsiflexion of the hand combined with flexion of the elbow caused an increase in tension only in the distal part. At all sites of the median nerve the median nerve upper limb tension test caused a significantly higher tension than the radial and ulnar nerve upper limb tension tests. This study provides insight in the normal distribution of tensile forces along the median nerve and can have clinical consequences. For differentiating nerve root from peripheral nerve lesions a specific provocative tension test for the median nerve is advocated. The results of this study provide a theoretical basis for differentiating between lesions in the proximal and distal parts of the median nerve

Alternative approaches to derive disability weights in injuries: do they make a difference?

BACKGROUND: In burden of disease studies, several approaches are used to assess disability weights, a scaling factor necessary to compute years lived with disability (YLD). The aim of this study was to quantify disability weights for injury consequences with two competing approaches, (a) standard QALY/DALY model (SQM) which derives disability weights from patient survey data and (b) the annual profile model (APM) which derives weights for the same patient data valued by a panel. METHODS: Disability weights were assessed using (a) EQ-5D data from a postal survey among 8,564 injury patients 2(1/2), 5, and 9 months after attending the Emergency Department, and (b) preferences of 143 laymen elicited with the time trade-off method. RESULTS: Compared with APM, SQM disability weights were consistently higher. YLD calculated with SQM disability weights was more than three times higher compared with YLD

Differential regulation of doxorubicin-induced mitochondrial dysfunction and apoptosis by Bcl-2 in mammary (MTLn3) cells

Toxicolog

Protocol voor monitoring landelijke mestmarkt onder een stelsel van gebruiksnormen : Versie 2009

Dit document beschrijft het protocol voor de monitoring van de landelijke mestmarkt onder het stelsel van gebruiksnormen. De doelen van het protocol zijn (i) het ontwikkelen van een gezamenlijke taal over de mestmarkt en (ii) het ontwikkelen van een gezamenlijke analyse van de mestmarkt. Omdat de mestdistributie in de mestmarkt een sleutelrol vervult, ligt de nadruk op de monitoring van de mestdistributie. De mestdistributie wordt via een analyse van de ‘Vervoersbewijzen Dierlijke Meststoffen’ (VDM’s) in kaart gebracht en vergeleken met resultaten van modelberekeningen. De VDM’s geven een beeld van de totale hoeveelheid mest die per jaar wordt geredistribueerd tussen bedrijven en tussen regio’s. Het model berekent de totale mestproductie, de hoeveelheid mest die op het bedrijf waar de mest is geproduceerd, kan worden geplaatst (bedrijfseigen mest) en de totale hoeveelheid mest die moet worden afgevoerd (bedrijfsvreemde mest). Confrontatie van deze verschillende ‘meststromen’ geeft een kwantitatief beeld van de mestproductie en mestplaatsing per regio en aldus van het evenwicht op de mestmarkt. Toepassing van het protocol garandeert dat de monitoring steeds op een uniforme wijze wordt uitgevoerd en dat een kwantitatief beeld wordt geschetst van de druk op de mestmarkt

Distinct intracellular signaling in Tumor Necrosis Factor-related Apoptosis-inducing Ligand- and CD95 Ligand-mediated apoptosis

Toxicolog

Spin glass overlap barriers in three and four dimensions

For the Edwards-Anderson Ising spin-glass model in three and four dimensions (3d and 4d) we have performed high statistics Monte Carlo calculations of those free-energy barriers $F^q_B$ which are visible in the probability density $P_J(q)$ of the Parisi overlap parameter $q$. The calculations rely on the recently introduced multi-overlap algorithm. In both dimensions, within the limits of lattice sizes investigated, these barriers are found to be non-self-averaging and the same is true for the autocorrelation times of our algorithm. Further, we present evidence that barriers hidden in $q$ dominate the canonical autocorrelation times.Comment: 20 pages, Latex, 12 Postscript figures, revised version to appear in Phys. Rev.