Short communication: minimum bactericidal concentration of disinfectants evaluated for bovine digital dermatitis-associated Treponema phagedenis-like spirochetes.

The bacterial spirochetes, Treponema spp., are thought to be a major contributor to the etiology of bovine digital dermatitis (DD), a skin disease with worldwide economic impact. Hoofbath strategies are commonly used in an attempt to control and prevent the development of DD and continuing research has been done to develop an optimal hoofbath strategy for this purpose.

P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis.

Background: Evaluate the potential role of p38 inhibitors for the treatment of osteoarthritis using an animal model of joint degeneration (iodoacetate-induced arthritis) and a pain model (Hargraeves assay).

Methods: P38 kinase activity was evaluated in a kinase assay by measuring the amount of phosphorylated substrate ATF2 using a phosphoATF2 (Thr71) specific primary antibody and an alkaline phosphate coupled secondary antibody and measuring the OD at 405 nm. TNFalpha and IL-1beta secretion from LPS stimulated THP-1 monocytic cells and human peripheral blood mononuclear cells were measured by ELISA.

Synthesis and evaluation of unsaturated caprolactams as interleukin-1beta converting enzyme (ICE) inhibitors.

Peptidomimetic compounds possessing a caprolactam ring constraint were prepared and evaluated as interleukin-1beta converting enzyme (ICE) inhibitors. The caprolactam ring was used to constrain the P3 region of our inhibitors. This strategy proved to be effective for the synthesis of ICE inhibitors, maintaining key hydrogen bond interactions with the enzyme and invoking a preferred conformation for binding.

Synthesis, characterization, and solution properties of a novel cross-bridged cyclam manganese(IV) complex having two terminal hydroxo ligands.

A novel monomeric tetravalent manganese complex with the cross-bridged cyclam ligand 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (Me2EBC), [Mn(IV)(Me2EBC)(OH)2](PF6)2, was synthesized by oxidation of Mn(II)(Me2EBC)Cl2 with H2O2 in the presence of NH4PF6)in aqueous solution.

Synthesis and evaluation of novel 8,5-fused bicyclic peptidomimetic compounds as interleukin-1beta converting enzyme (ICE) inhibitors.

An 8,5-fused bicyclic peptidomimetic ring system generated by a stereoselective ring metathesis reaction was elaborated into potent inhibitors of interleukin-1beta converting enzyme (ICE, caspase-1). Multiple compounds were found that exhibited ICE IC50 values < 10 nM and were selective over caspase-3 and caspase-8. These active analogs generally possessed good activity (IC50 values < 100 nM) in a whole cell assay measuring IL-1beta production.