The innate immune system is comprised of many components that function coordinately to prevent bacterial sepsis. However, thermal injury suppresses many of these factors, and the opportunistic pathogen Pseudomonas aeruginosa takes advantage of this condition, making it one of the leading causes of morbidity and mortality in the setting of thermal injury. P. aeruginosa is extremely efficient at colonizing burn wounds, spreading systemically, and causing sepsis, which often results in a systemic inflammatory response, multiple-organ failure, and death. The pathogenicity of P. aeruginosa is due to the arsenal of virulence factors produced by the pathogen and the immunocompromised state of the host. Syndecan 1 is a major heparan sulfate proteoglycan present on many host cells involved in thermal injury. Syndecan 1 anchored to the cell surface can be cleaved in a process termed ectodomain shedding. Syndecan 1 shedding results in the release of intact, soluble proteoglycan ectodomains that have diverse roles in innate immunity. Here we show for the first time that thermal injury results in shedding of syndecan 1 from host tissue. Our data show that syndecan 1 null mice are significantly less susceptible to P. aeruginosa infection than their wild-type counterparts, as demonstrated by (i) significantly lower mortality; (ii) absence of systemic spread of P. aeruginosa; and (iii) significant reductions in some proinflammatory cytokines. These results suggest that shed syndecan 1 plays an important role in the pathogenesis of P. aeruginosa infection of thermal injury and that syndecan 1-neutralizing agents may be effective supplements to current P. aeruginosa treatments.The gram-negative opportunistic pathogen Pseudomonas aeruginosa is particularly prevalent in burn wound infections. P. aeruginosa bacteremia is one of the leading causes of morbidity and mortality in the setting of thermal injury. It often causes multiorgan failure and results in mortality rates of up to 50% (2,25,26,39). The extensive damage induced during P. aeruginosa infection is due to the ability of the microorganism to produce a large array of virulence factors (25) and the immunocompromised state of the individual. However, the increased ability of P. aeruginosa over many other pathogens to cause sepsis in thermally injured individuals is not fully understood.
An argument that what is usually dismissed as the “mystical shell” of Hegel's thought—the concept of absolute knowledge—is actually its most “rational kernel.” This book sets out from a counterintuitive premise: the “mystical shell” of Hegel's system proves to be its most “rational kernel.” Hegel's radicalism is located precisely at the point where his thought seems to regress most. Most current readings try to update Hegel's thought by pruning back his grandiose claims to “absolute knowing.” Comay and Ruda invert this deflationary gesture by inflating what seems to be most trivial: the absolute is grasped only in the minutiae of its most mundane appearances. Reading Hegel without presupposition, without eliminating anything in advance or making any decision about what is essential and what is inessential, what is living and what is dead, they explore his presentation of the absolute to the letter. The Dash is organized around a pair of seemingly innocuous details. Hegel punctuates strangely. He ends the Phenomenology of Spirit with a dash, and he begins the Science of Logic with a dash. This distinctive punctuation reveals an ambiguity at the heart of absolute knowing. The dash combines hesitation and acceleration. Its orientation is simultaneously retrospective and prospective. It both holds back and propels. It severs and connects. It demurs and insists. It interrupts and prolongs. It generates nonsequiturs and produces explanations. It leads in all directions: continuation, deviation, meaningless termination. This challenges every cliché about the Hegelian dialectic as a machine of uninterrupted teleological progress. The dialectical movement is, rather, structured by intermittency, interruption, hesitation, blockage, abruption, and random, unpredictable change—a rhythm that displays all the vicissitudes of the Freudian drive.
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