The Journal of surgical research
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Activated protein C (aPC) confers survival benefit in patients with sepsis, yet its protective mechanism(s) remain unclear. Herein, we determined time-dependent severity of renal dysfunction during polymicrobial sepsis. We hypothesized aPC restores renal function by preserving organ architecture and reducing inflammation. ⋯ Our data demonstrate that renal dysfunction occurs as early as 6 h following sepsis and continues thereafter. Treatment with aPC attenuated INFγ and IL-1β changes, and preserved renal function in sepsis. These data suggest aPC may confer a survival advantage by reducing systemic inflammation and, in doing so, preserving organ function.
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The breakdown of skin microcirculation and the leukocyte-endothelium interaction are assumed to play a key role in the pathophysiology of frostbite injuries. However, little is known as yet. The aim was to develop an in vivo frostbite model to monitor microcirculatory changes and angiogenesis after frostbite injury. ⋯ This novel frostbite model provides a simple and nonetheless highly effective technique of creating locally limited reproducible frostbite injuries using a no touch technique. Tissue damage can be fully attributed to the thermal trauma, and the model allows repetitive intravital fluorescent microscopy of the microcirculation, leukocyte-endothelium interaction, and angiogenesis.
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Some of the postulated molecular mechanisms of sepsis progression are linked with the imbalance between reactive oxygen species (ROS) production and its degradation by cellular antioxidant pathways. Some studies have correlated plasma oxidative stress, inflammatory markers, and clinical markers of organ failure, but none performed this in a systematic way, determining in situ oxidative and inflammatory markers and correlating these with markers of organ failure. ⋯ Despite the general occurrence of oxidative damage in different organs during sepsis development and a positive correlation between oxidative markers and organ injury, antioxidant effects seemed to depend not only on the diminution of oxidative damage but also on its anti-inflammatory activity.
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Acute kidney injury (AKI) is a common complication of hospitalized patients, and clinical outcomes remain poor despite advances in renal replacement therapy. The accepted pathophysiology of AKI in the setting of sepsis has evolved from one of simple decreased renal blood flow to one that involves a more complex interaction of intra-glomerular microcirculatory vasodilation combined with the local release of inflammatory mediators and apoptosis. ⋯ These interactions are reflected by genomic changes and abnormal rates of cellular apoptosis in distant organs including the lungs, heart, gut, liver, and central nervous system. The purpose of this article is to review the influence of AKI, particularly sepsis-associated AKI, on inter-organ crosstalk in the context of systemic inflammation and multiple organ failure (MOF).