Targeting the Endothelin A Receptor in IgA Nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and carries a substantial risk of kidney failure. New agency-approved therapies, either specifically for IgAN or for chronic kidney disease (CKD) in general, hold out hope for mitigating renal deterioration in patients with IgAN. The latest addition to this therapeutic armamentarium targets the endothelin-A receptor (ETAR). Activation of ETAR on multiple renal cell types elicits a host of pathophysiological effects, including vasoconstriction, cell proliferation, inflammation, apoptosis, and fibrosis. Blockade of ETAR is renoprotective in experimental models of IgAN and reduces proteinuria in patients with IgAN. This review discusses the evidence supporting the use of ETAR blockade in IgAN as well as addressing the potential role for this class of agents among the current and emerging therapies for treating this disorder.</p

Targeting the Endothelin A Receptor in IgA Nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and carries a substantial risk of kidney failure. New agency-approved therapies, either specifically for IgAN or for chronic kidney disease (CKD) in general, hold out hope for mitigating renal deterioration in patients with IgAN. The latest addition to this therapeutic armamentarium targets the endothelin-A receptor (ETAR). Activation of ETAR on multiple renal cell types elicits a host of pathophysiological effects, including vasoconstriction, cell proliferation, inflammation, apoptosis, and fibrosis. Blockade of ETAR is renoprotective in experimental models of IgAN and reduces proteinuria in patients with IgAN. This review discusses the evidence supporting the use of ETAR blockade in IgAN as well as addressing the potential role for this class of agents among the current and emerging therapies for treating this disorder.</p

Temperature dependence and mechanisms for vortex pinning by periodic arrays of Ni dots in Nb films

Pinning interactions between superconducting vortices in Nb and magnetic Ni dots were studied as a function of current and temperature to clarify the nature of pinning mechanisms. A strong current dependence is found for a square array of dots, with a temperature dependent optimum current for the observation of periodic pinning, that decreases with temperature as (1-T/Tc)3/2. This same temperature dependence is found for the critical current at the first matching field with a rectangular array of dots. The analysis of these results allows to narrow the possible pinning mechanisms to a combination of two: the interaction between the vortex and the magnetic moment of the dot and the proximity effect. Moreover, for the rectangular dot array, the temperature dependence of the crossover between the low field regime with a rectangular vortex lattice to the high field regime with a square configuration has been studied. It is found that the crossover field increases with decreasing temperature. This dependence indicates a change in the balance between elastic and pinning energies, associated with dynamical effects of the vortex lattice in the high field range.Comment: 12 text pages (revtex), 6 figures (1st jpeg, 2nd-6th postscript) accepted in Physical Review

Magnetar Driven Bubbles and the Origin of Collimated Outflows in Gamma-ray Bursts

We model the interaction between the wind from a newly formed rapidly rotating magnetar and the surrounding supernova shock and host star. The dynamics is modeled using the two-dimensional, axisymmetric thin-shell equations. In the first ~10-100 seconds after core collapse the magnetar inflates a bubble of plasma and magnetic fields behind the supernova shock. The bubble expands asymmetrically because of the pinching effect of the toroidal magnetic field, just as in the analogous problem of the evolution of pulsar wind nebulae. The degree of asymmetry depends on E_mag/E_tot. The correct value of E_mag/E_tot is uncertain because of uncertainties in the conversion of magnetic energy into kinetic energy at large radii in relativistic winds; we argue, however, that bubbles inflated by newly formed magnetars are likely to be significantly more magnetized than their pulsar counterparts. We show that for a ratio of magnetic to total power supplied by the central magnetar L_mag/L_tot ~ 0.1 the bubble expands relatively spherically. For L_mag/L_tot ~ 0.3, however, most of the pressure in the bubble is exerted close to the rotation axis, driving a collimated outflow out through the host star. This can account for the collimation inferred from observations of long-duration gamma-ray bursts (GRBs). Outflows from magnetars become increasingly magnetically dominated at late times, due to the decrease in neutrino-driven mass loss as the young neutron star cools. We thus suggest that the magnetar-driven bubble initially expands relatively spherically, enhancing the energy of the associated supernova, while at late times it becomes progressively more collimated, producing the GRB.Comment: 14 pages, 8 figures, accepted for publication in MNRA