Adherence and health care costs.

Medication nonadherence is an important public health consideration, affecting health outcomes and overall health care costs. This review considers the most recent developments in adherence research with a focus on the impact of medication adherence on health care costs in the US health system. We describe the magnitude of the nonadherence problem and related costs, with an extensive discussion of the mechanisms underlying the impact of nonadherence on costs.

Cowhage-evoked itch is mediated by a novel cysteine protease: a ligand of protease-activated receptors.

Cowhage spicules provide an important model for histamine-independent itch. We determined that the active component of cowhage, termed mucunain, is a novel cysteine protease. We isolated mucunain and demonstrate that both native and recombinant mucunain evoke the same quality of itch in humans.

Maxadilan, a PAC1 receptor agonist from sand flies.

In 1991, a potent 61 amino acid vasodilator peptide, named maxadilan, was isolated from the salivary glands of the sand fly. Subsequently, it was shown that this peptide specifically and potently activated the mammalian PAC1 receptor, one of the three receptors for PACAP. These studies and the link between maxadilan and leishmaniasis are discussed.

TRP-ing up melanophores: TRPM7, melanin synthesis, and pigment cell survival.

McNeill et al. (2007, this issue) dissect the potential role of TRPM7 ion channels in pigment cells by studying the phenotype of zebrafish trpm7 mutant embryos. They demonstrate that 1-phenyl-2-thiourea, a known melanin synthesis inhibitor, prevents melanophore cell death in these mutants.

Functional analysis of recombinant mutants of maxadilan with a PAC1 receptor-expressing melanophore cell line.

Maxadilan, a 61-amino-acid vasodilatory peptide, was initially isolated from the salivary glands of the sand fly Lutzomyia longipalpis. Although its primary sequence has no homology to that of pituitary adenylate cyclase-activating peptide, maxadilan is an agonist for the PAC1 receptor. A total of 58 substitution and deletion mutants was engineered in an effort to determine which residues were important for receptor activation.

Identification of novel hexapeptide agonists at the Xenopus laevis melanophore melanocortin receptor.

We used a combinatorial chemical approach to identify novel agonists for the endogenous melanocortin receptor expressed in Xenopus laevis melanophores. A random one-bead one-compound hexapeptide library was screened to detect new molecules able to induce pigment dispersion in melanophores. Our approach led to the discovery of seven related novel peptides able to stimulate pigment dispersion with EC50 in the range of 0.

Nitric oxide is toxic to melanocytes in vitro.

Nitric oxide is a diffusible gaseous mediator generated from l-arginine by inducible and constitutive nitric oxide synthases. It has been associated with cytotoxic effects. Inflammatory cells and Langerhans cells can express the inducible form of nitric oxide synthase and produce large quantities of nitric oxide.