Other Research and Treatment Strategies

Several studies have further evaluated strategies against the effects of endotoxin. These include oral feeding with glutamine in an endotoxin animal model, blockade of the testosterone receptor, and blocking calcium channels with diltiazem or verapamil.

A pilot clinical project evaluating the effects of methylene blue in human septic shock has been completed and appears to counteract myocardial depression, and maintain oxygen transport, through methylene blue's effect on inhibiting nitric oxide.

Several other studies reported this year have shown elevated levels of heat shock proteins in association with survival in sepsis, and increased activated leukocyte microparticles in sepsis. The relationship of nitric oxide to p38 MAP kinase activation and the effects of secretory IgA on maintaining the intact intestinal barrier after ischemia and reperfusion and bacterial challenge have also been further clarified.

Two studies evaluated the effects of granulocyte colony stimulating factor (G-CSF). The first demonstrates that hemopoietic failure after burn wound infection is not related to defective endogenous G-CSF release. Of concern, G-CSF administered in animal models impairs immunoglobulin synthesis after a burn injury and raises caution regarding its mechanism before proceeding to clinical trials.

One recent study found that a single allele in the tumor necrosis factor-alpha promoter region is associated with increased risk for sepsis. Other studies have documented an association between intranuclear NF-kB and systemic inflammatory response syndrome or multiple-organ failure. It is increasingly clear that both genetic effects and specific intracellular activation states drive the inflammatory response, and our ability to describe these in time and understand the mechanisms for manipulation will allow more precise interaction with this complex clinical problem.

References

1. Sessler CN, Shepherd W. New concepts in sepsis. Curr Opin Crit Care (United States) Oct 2002; 8(5):465-72.

2. Ely EW, Laterre PF, Angus DC et al. Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis. Crit Care Med (United States) Jan 2003; 31(1):12-9.

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