Mechanism of alternative complement pathway dysregulation by a phosphorothioate oligonucleotide in monkey and human serum.

The species sensitivity and mechanism of complement pathway activation by a phosphorothioate oligonucleotide were investigated in monkey and human serum. Increasing concentrations of a phosphorothioate oligonucleotide, ISIS 2302, were incubated in either monkey or human serum. Complement activation in monkey serum was selective for the alternative pathway and occurred at concentrations ≥ 50 μg/mL ISIS 2302.

Dietary aspartyl-phenylalanine-1-methyl ester delays osteoarthritis and prevents associated bone loss in STR/ORT mice.

Objective: STR/ORT mice provide a well-known model for murine idiopathic OA, with histological joint lesions resembling those of human OA. This model was used to investigate protective effects of the dipeptide aspartyl-phenylalanine-1-methyl ester (Asp-Phe-OMe or aspartame) via the oral route vs a regular diet.

Methods: STR/ORT mice were housed individually and fed diets with or without Asp-Phe-OMe (4 mg/kg), after weaning at the age of 3 weeks, until 15 months of age (average of 20 animals per group).

Pancreatic enzymes generate cytotoxic mediators in the intestine.

Recent evidence indicates that shock is accompanied by a failure of the mucosal barrier in the intestine and entry of pancreatic digestive enzymes into the wall of the intestine. To investigate the formation of cytotoxic mediators produced by enzymatic digestion of the intestine, we applied homogenates of rat small intestinal wall to human neutrophils and used flow cytometry measurements of propidium iodide uptake to determine cytotoxicity. We show that homogenates of the small intestine after ischemia by occlusion of the superior mesenteric and celiac arteries for 3 h, but not without ischemia, are cytotoxic.

Intraluminal pancreatic serine protease activity, mucosal permeability, and shock: a review.

Shock states are characterized by a pronounced activation of numerous cell types that lead to an acute inflammatory reaction. The exact mechanism by which these inflammatory cells are activated is not known. Numerous studies have implicated the gastrointestinal tract as one of the main sites for the generation of inflammatory mediators and initiation of an acute systemic response.