Role of the endothelium and COX-1 in prostacyclin generation by whole vessels stimulated with different agonists

Prostacyclin is an important cardioprotective hormone produced by the vascular wall, whose synthesis is dependent on cyclo-oxygenase (COX) enzymes. In healthy vessels the endothelium is thought to be the main site of prostacyclin release (Moncada et al 1977). Two isoforms of COX exist, and we have recently published data demonstrating that it is COX-1 rather than COX-2 that drives the production of prostacyclin in mouse aorta (Kirkby et al 2012). In this study we aimed to extend these observations by investigating what proportion of the COX-1 driven aortic prostacyclin production that comes from the endothelium versus the rest of the vessel wall (smooth muscle layers and adventitia). To do this, we explored how removal of the endothelium would influence the ability of aortic tissue to release prostacyclin in response to a range of agonists that are known to activate the endothelium and the vessel wallNon peer reviewe

Role of shear stress in endothelial cell morphology and expression of cyclooxygenase isoforms

MEDLINE® is the source for the MeSH terms of this document.Objective-: The goal of this study was to examine the effect of chronic heterogeneous shear stress, applied using an orbital shaker, on endothelial cell morphology and the expression of cyclooxygenases 1 and 2. Methods and results-: Porcine aortic endothelial cells were plated on fibronectin-coated Transwell plates. Cells were cultured for up to 7 days either under static conditions or on an orbital shaker that generated a wave of medium inducing shear stress over the cells. Cells were fixed and stained for the endothelial surface marker CD31 or cyclooxygenases 1 and 2. En face confocal microscopy and scanning ion conductance microscopy were used to show that endothelial cells were randomly oriented at the center of the well, aligned with shear stress nearer the periphery, and expressed cyclooxygenase-1 under all conditions. Lipopolysaccharide induced cyclooxygenase-2 and the production of 6-keto-prostaglandin F1α in all cells. Conclusion-: Cyclooxygenase-1 is expressed in endothelial cells cultured under chronic shear stress of high or low directionality.Peer reviewedSubmitted Versio

Een noodverband tegen hoog water: waterkennis, beleid en politiek rond noodoverloopgebieden

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The Glauber model and the heavy ion reaction cross section

We reexamine the Glauber model and calculate the total reaction cross section as a function of energy in the low and intermediate energy range, where many of the corrections in the model, are effective. The most significant effect in this energy range is by the modification of the trajectory due to the Coulomb field. The modification in the trajectory due to nuclear field is also taken into account in a self consistent way. The energy ranges in which particular corrections are effective, are quantified and it is found that when the center of mass energy of the system becomes 30 times the Coulomb barrier, none of the trajectory modification to the Glauber model is really required. The reaction cross sections for light and heavy systems, right from near coulomb barrier to intermediate energies have been calculated. The exact nuclear densities and free nucleon-nucleon (NN) cross sections have been used in the calculations. The center of mass correction which is important for light systems, has also been taken into account. There is an excellent agreement between the calculations with the modified Glauber model and the experimental data. This suggests that the heavy ion reactions in this energy range can be explained by the Glauber model in terms of free NN cross sections without incorporating any medium modification.Comment: RevTeX, 21 pages including 9 Postscript figures, submitted to Phys. Rev.

Shape programming for narrow ribbons of nematic elastomers

Using the theory of Γ-convergence, we derive from three-dimensional elasticity new one-dimensional models for non-Euclidean elastic ribbons, i.e., ribbons exhibiting spontaneous curvature and twist. We apply the models to shape-selection problems for thin films of nematic elastomers with twist and splay-bend texture of the nematic director. For the former, we discuss the possibility of helicoid-like shapes as an alternative to spiral ribbons

Damage to Broca’s area does not contribute to long-term speech production outcome after stroke

Broca’s area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca’s area damage is best explained by the combination of damage to Broca’s area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca’s two historic cases. Here, we dissociate the effect of damage to Broca’s area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca’s area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the ComprehensiveAphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predictedby the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca’s area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca’s area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca’s area than after damage to Broca’s area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca’s area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca’s area; and (iii) the prior association between persistent speech production impairments and Broca’s area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus

Vancomycin exposure and acute kidney injury outcome: A Snapshot From the CAMERA2 Study

Among patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia from a prospective randomized clinical trial, acute kidney injury (AKI) rates increased with increasing vancomycin exposure, even within the therapeutic range. AKI was independently more common for the (flu)cloxacillin group. Day 2 vancomycin AUC ≥470 mg·h/L was significantly associated with AKI, independent of (flu)cloxacillin receipt