Tß4-Ac-SDKP pathway: Any relevance for the cardiovascular system?

The last 20 years witnessed the emergence of the thymosin ß4 (Tß4)-N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) pathway as a new source of future therapeutic tools to treat cardiovascular and renal diseases. In this review article, we attempted to shed light on the numerous experimental findings pertaining to the many promising cardiovascular therapeutic avenues for Tß4 and (or) its N-terminal derivative, Ac-SDKP. Specifically, Ac-SDKP is endogenously produced from the 43-amino acid Tß4 by 2 successive enzymes, meprin α and prolyl oligopeptidase. We also discussed the possible mechanisms involved in the Tß4-Ac-SDKP-associated cardiovascular biological effects. In infarcted myocardium, Tß4 and Ac-SDKP facilitate cardiac repair after infarction by promoting endothelial cell migration and myocyte survival. Additionally, Tß4 and Ac-SDKP have antifibrotic and anti-inflammatory properties in the arteries, heart, lungs, and kidneys, and stimulate both in vitro and in vivo angiogenesis. The effects of Tß4 can be mediated directly through a putative receptor (Ku80) or via its enzymatically released N-terminal derivative Ac-SDKP. Despite the localization and characterization of Ac-SDKP binding sites in myocardium, more studies are needed to fully identify and clone Ac-SDKP receptors. It remains promising that Ac-SDKP or its degradation-resistant analogs could serve as new therapeutic tools to treat cardiac, vascular, and renal injury and dysfunction to be used alone or in combination with the already established pharmacotherapy for cardiovascular diseases.

Tuning the adhesion of layer-by-layer films to the physicochemical properties of inner limiting membranes using nanoparticles.

Retinal trauma is a serious concern for patients undergoing inner limiting membrane (ILM) peeling to correct for various vitreoretinal interface conditions. This mechanical trauma can be prevented by modifying the surface of surgical instruments to increase adhesion to the ILM. To this effect, we have studied the effects of roughness and surface charge on the adhesive properties of ILMs by utilizing layer-by-layer (LbL) films with embedded gold nanoparticles (LbL-AuNP films). LbL films were assembled on atomic force microscopy (AFM) tipless cantilevers. Topographical analysis of these films, with and without nanoparticles, showed that LbL films with nanoparticles had a higher rms roughness compared to films alone or unmodified cantilevers. Nanoparticle-modified LbL films significantly increased the adhesion forces at the cantilever-ILM interface, compared to LbL films without particles. Surprisingly, adsorption of gold nanoparticles onto the AFM cantilevers caused increases in adhesion forces greater than those measured with LbL-AuNP films. These results have important implications for the design of surface modifications for vitreoretinal surgical instruments.

Emergency Use Authority and 2009 H1N1 influenza.

This article discusses the steps that the Department of Health and Human Services follows to authorize emergency use of products under section 564 of the Federal Food, Drug and Cosmetic Act through Emergency Use Authorizations. We provide examples of when the department might authorize such emergency use and describe the products for which the department has authorized emergency use for the current H1N1 influenza pandemic as of September 1, 2009.