Interleukin 4 and interleukin 13 downregulate the lipopolysaccharide-mediated inflammatory response by human gestation-associated tissues.

Inflammation is a key feature of preterm and term labor. Proinflammatory mediators are produced by gestation-associated tissues in response to pathogen-associated molecular patterns and damage-associated molecular patterns. Interleukin (IL)4, IL10, and IL13 are anti-inflammatory cytokines with potential as anti-inflammatory therapies to prevent preterm birth.

Chromophores in operative surgery: Current practice and rationalized development.

Background: Chromophore-containing molecules feature extensively in surgical practice, with synthetic dyes gaining popularity over endogenous optical adjuncts. New applications for chromophores in diagnostics and operative treatment exploit unique chemical structures suited for illuminating target tissues beyond the visual spectrum, ranging from ultraviolet (UV) to near-infrared (NIR). This review outlines the rationale for surgical chromophore application, the weaknesses and risks in each class of these compounds, and areas of foreseeable potential for employment of specialized contrast agents.

Innate immunity and the sensing of infection, damage and danger in the female genital tract.

Tissue homeostasis in the female genital tract is challenged by infection, damage, and even physiological events during reproductive cycles. We propose that the evolutionarily ancient system of innate immunity is sufficient to sense and respond to danger in the non-pregnant female genital tract. Innate immunity produces a rapidly inducible, non-specific response when cells sense danger.

Enhanced paracellular transport of insulin can be achieved via transient induction of myosin light chain phosphorylation.

The intestinal epithelium functions to effectively restrict the causal uptake of luminal contents but has been demonstrated to transiently increase paracellular permeability properties to provide an additional entry route for dietary macromolecules. We have examined a method to emulate this endogenous mechanism as a means of enhancing the oral uptake of insulin. Two sets of stable Permeant Inhibitor of Phosphatase (PIP) peptides were rationally designed to stimulate phosphorylation of intracellular epithelial myosin light chain (MLC) and screened using Caco-2 monolayers in vitro.

Myosin light chain kinase inhibition: correction of increased intestinal epithelial permeability in vitro.

Purpose: To examine whether myosin light chain kinase (MLCK) inhibitors can reduce intestinal epithelial permeability increases in vitro.

Materials And Methods: Isolated rat, mouse and human colonic tissue mucosae and Caco-2 monolayers were exposed to cytochalasin D (cD) and sodium caprate (C10), in the absence and presence of the MLCK inhibitors, ML-9 and D PIK. Transepithelial electrical resistance (TEER) and Papp of [14C]-mannitol or FITC-dextran 4000 (FD-4) were measured.

A strategy to identify stable membrane-permeant peptide inhibitors of myosin light chain kinase.

Purpose: A peptide inhibitor of myosin light chain kinase (MLCK), termed membrane permeant inhibitor of myosin light chain kinase (PIK), has previously been demonstrated to correct paracellular barrier defects associated with in vitro cell models of infectious and inflammatory intestinal disease. The current study describes a strategy to identify stable analogues of PIK required for future in vivo studies that has resulted in the identification of two promising candidates.

Methods: Because PIK functions at an intracellular site of epithelial cells and is envisaged to be administered orally, hydrolysis patterns were determined for PIK in both extracts of homogenized Caco-2 (a human intestinal epithelial cell line) and in luminal secretions isolated from rat intestine.