Current opinion in critical care
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Curr Opin Crit Care · Apr 2003
ReviewRole of poly(adenosine diphosphate-ribose) polymerase 1 in septic peritonitis.
Peritonitis generally results from gastrointestinal perforation, with systemic sepsis developing over hours or days from an initially localized nidus of infection. The consecutive inflammatory response induces the widespread generation of oxidants and free radicals, which are potent inducers of breaks and nicks in double-stranded DNA. ⋯ In parallel, poly(ADP-ribose) polymerase 1 positively regulates inflammatory signal transduction pathways through a functional association with the transcription factor nuclear factor kappaB, resulting in a progressive amplification of local inflammation. Recent data indicate that these molecular mechanisms are instrumental in the development of cardiovascular collapse and multiple organ dysfunction in sepsis, supporting the view that pharmacologic inhibitors of poly(ADP-ribose) polymerase 1 may represent useful tools for the treatment of this condition.
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To outline evidence that suggests increased intestinal epithelial apoptosis (programmed cell death) plays an important role in critical illness of infectious and noninfectious origin. ⋯ These animal studies offer a possible new mechanism underlying the gut's role as the "motor" of the systemic inflammatory response syndrome and suggest that intestinal epithelial apoptosis may be a novel therapeutic target in future critical care research.
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Curr Opin Crit Care · Apr 2003
ReviewEffect of estradiol administration on splanchnic perfusion after trauma-hemorrhage and sepsis.
This review focuses on the latest mechanistic understanding of the effects of estradiol on the splanchnic circulation and the possibility of estradiol treatment as an adjunct for the treatment of trauma-hemorrhage and sepsis. ⋯ Trauma-hemorrhage results in decreased circulating blood volume. In contrast, sepsis is an inflammatory state mainly mediated by bacterial products. However, these divergent insults show similar pathophysiologic alterations in terms of the splanchnic circulation. Because estradiol effectively protects the organs from circulatory failure after various adverse circulatory conditions, many studies are being performed to clarify the molecular mechanism of estradiol action with regard to tissue circulation. Estradiol improves the macro- and microcirculation of the splanchnic organs by multiple mechanisms. Nonetheless, it remains unclear which mechanism plays the most important role in the treatment of trauma-hemorrhage and sepsis. Additional studies are required to elucidate the precise mechanism of estradiol action and to determine the usefulness of estradiol treatment for severe hemorrhage and sepsis in patients.