Vaccine adjuvant activity of 3M-052: an imidazoquinoline designed for local activity without systemic cytokine induction.

The human Toll-like receptors (TLRs) are a family of receptors, which sense the presence of various structural elements of pathogens and damaged or effete components in the host. As they do so, they activate two critical arms of host defense, the rapid innate immune response and an adaptive immune response. The innate immune response is typified by the generation of Th1 cytokines, chemokines and type 1 interferons.

In vivo fibroplasia of a porous polymer in the cornea.

We have developed a melt-blown fibrous construction of polybutylene/polypropylene in which we previously demonstrated keratocyte ingrowth and collagen synthesis in vitro. In the present studies, we evaluated this material in vivo in interlamellar corneal pockets for periods of up to six months. By day 42, the porous interstices of the disc were heavily populated with keratocytes.

In vitro evaluation of fibroplasia in a porous polymer.

We evaluated a polybutylene/polypropylene blend in a blown microfiber configuration in vitro for potential use as the peripheral area of a keratoprosthetic device. Material properties such as ultimate tensile strength and ultimate elongation were measured. Stromal fibroblasts were seeded onto the material in vitro, and cell proliferation between uncoated and Type I collagen coated discs did not differ significantly.

Development of a biopolymeric keratoprosthetic material. Evaluation in vitro and in vivo.

Based on the results of in vitro and in vivo experiments, we have determined that the optimal material for the central transparent portion of a perforating keratoprosthesis is a polyvinyl alcohol copolymer hydrogel. The material supports the maintenance and growth of corneal epithelium in vitro as shown by population doublings and transmission electron microscopy. Discs preseeded with epithelial cells were cultured in vitro and transplanted into rabbit corneas.

Substrate specificity of pyroglutamylaminopeptidase.

Three synthetic peptides (compounds 4-6) were tested as substrates of pyroglutamylaminopeptidase. In addition, inhibition of the hydrolysis of these substrates by compounds 8 and 9 was also examined. The enzyme does not appreciably catalyze the hydrolysis of peptides with six-membered ureido rings at the amino terminus, but it tolerates well a five-membered ureido ring at this position.