Relation of In Vitro Inhibition by Chelates of Clostridium perfringens α-Toxin to Their Ability to Protect Against Experimental Toxemia

The inhibition of Clostridium perfringens alpha-toxin by ethylenediaminetetraacetate (EDTA) and diethylenetriaminepentacetate (DTPA) was studied utilizing three different in vitro assay procedures: diffusion on egg yolk-agar, disintegration of muscle sections, and manometric assay with partially purified lecithin as substrate. DTPA was 10 to 20 times more efficient as an inhibitor than EDTA in systems containing relatively large amounts of calcium; these observations were similar to those observed in previous in vivo protection studies. A number of other chelating agents were tested for their ability to inhibit alpha-toxin in vitro and protect mice against it; the chelating agents which were the most efficient in vitro inhibitors had the greatest in vivo protective ability.     

Passive and active components of the internal moment developed about the ankle joint during human ambulation

The internal moment developed about a joint during a functional activity is the result of contraction of muscles and the visco-elastic properties of the joint and its surrounding soft tissues. In this study, the contribution of each one of these mechanisms to the total internal moment developed about the ankle joint during human level walking was assessed. The results indicate that during normal level walking the internal moment about the ankle is mainly due to contraction of muscles surrounding the joint. The contribution of the passive component was found to be negligible. These results, however, were found to be different for the pathological case tested. The results indicated that in a subject with a mild equinus ankle deformity, a substantial portion (21%) of the total internal moment was contributed by the passive resistance of the joint and its surrounding structures.     

Pseudomonas aeruginosa Type III secretion system interacts with phagocytes to modulate systemic infection of zebrafish embryos

Pseudomonas aeruginosa is an opportunistic human pathogen that can cause serious infection in those with deficient or impaired phagocytes. We have developed the optically transparent and genetically tractable zebrafish embryo as a model for systemic P. aeruginosa infection. Despite lacking adaptive immunity at this developmental stage, zebrafish embryos were highly resistant to P. aeruginosa infection, but as in humans, phagocyte depletion dramatically increased their susceptibility. The virulence of an attenuated P. aeruginosa strain lacking a functional Type III secretion system was restored upon phagocyte depletion, suggesting that this system influences virulence through its effects on phagocytes. Intravital imaging revealed bacterial interactions with multiple blood cell types. Neutrophils and macrophages rapidly phagocytosed and killed P. aeruginosa , suggesting that both cell types play a role in protection against infection. Intravascular aggregation of erythrocytes and other blood cells with resultant circulatory blockage was observed immediately upon infection, which may be relevant to the pathogenesis of thrombotic complications of human P. aeruginosa infections. The real-time visualization capabilities and genetic tractability of the zebrafish infection model should enable elucidation of molecular and cellular details of P. aeruginosa pathogenesis in conditions associated with neutropenia or impaired phagocyte function.