Rotigotine transdermal system: developing continuous dopaminergic delivery to treat Parkinson's disease and restless legs syndrome.

Rotigotine is a nonergoline dopamine receptor agonist with structural similarity to dopamine. Rotigotine binds to the D1 through D5 dopamine receptors, having several times more affinity than dopamine does to the D2 and D3 receptors. Although rotigotine was demonstrated to restore locomotor activity in animal models of Parkinson's disease (PD), the rapid metabolism of rotigotine limited the development of an orally administered formulation.

Interaction of ICAM-1 with beta 2-integrin CD11c/CD18: characterization of a peptide ligand that mimics a putative binding site on domain D4 of ICAM-1.

The integrin CD11c/CD18 plays a role in leukocyte and cell matrix adhesion and is highly expressed in certain hematopoietic malignancies. To better characterize ligand binding properties, we panned random peptide phage-display libraries over purified CD11c/CD18. We identified a phage expressing the circular peptide C-GRWSGWPADL-C.

Neutrophil transendothelial migration and alteration in vascular permeability: focus on neutrophil-derived azurocidin.

Infiltration and accumulation of polymorphonuclear leukocytes within the tissues is a hallmark of the acute inflammatory response. A prominent feature of acute inflammation is enhanced vascular permeability resulting in edema formation. Such changes in vascular permeability have been known to be dependent upon polymorphonuclear leukocyte interactions with the vascular endothelium.

Neutrophil transepithelial migration: evidence for sequential, contact-dependent signaling events and enhanced paracellular permeability independent of transjunctional migration.

Active migration of polymorphonuclear leukocytes (PMN) through the intestinal crypt epithelium is a hallmark of inflammatory bowel disease and correlates with patient symptoms. Previous in vitro studies have shown that PMN transepithelial migration results in increased epithelial permeability. In this study, we modeled PMN transepithelial migration across T84 monolayers and demonstrated that enhanced paracellular permeability to small solutes occurred in the absence of transepithelial migration but required both PMN contact with the epithelial cell basolateral membrane and a transepithelial chemotactic gradient.