Through gene and protein analyses in both septic mice and humans, scientists found that cases of severe sepsis featured a unique attribute: the genes within platelets were triggered to produce a protein known as granzyme B, which has been shown in previous studies to contribute to cell death as part of the body's immune response to cancer and viruses. During sepsis, platelets collect within major organs including the spleen, an important infection-fighting organ. As they collect and come into contact with the organ's cells, the granzyme B, if present, will cause the organ's cells to die. Previous research has shown that that this factor may be a major contributor to organ failure. Granzyme B was only detected in humans and mice with the most severe sepsis.
"Detection of granzyme B in platelets could be a huge step forward in battling sepsis," said Dr. Freishtat. "First, as a prognostic indicator, the protein's presence could show more aggressive treatments are needed right off the bat. Eventually, perhaps this knowledge will help us find a way to prevent organ failure by targeting interventions directly at the platelets and granzyme B production."
Endothelial activation and dysfunction play a key role in the pathogenesis of sepsis. During septic shock, endothelial dysfunction is involved in microcirculation impairment and organ dysfunction. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have several potentially important effects on endothelial function and are implicated in physiological regulation and disease pathophysiology. The imbalance between the production of ROS and their effective removal by non-enzymatic and enzymatic antioxidants systems could induce endothelial dysfunction with alterations of vascular tone, increases in cell adhesion properties (leukocytes and platelet adhesion), increase in vascular wall permeability and a pro-coagulant state. Increasing evidence supports the idea that the principal cause of EC dysfunction during sepsis is cell injury. ROS and RNS contribute to mitochondrial dysfunction by a range of mechanisms and induce both necrotic and apoptotic cell death. Understanding the mechanisms underlying the generation of ROS and RNS in endothelial cells and the causes of endothelial dysfunction in sepsis may help provide therapeutic strategies to tackle endothelial dysfunction and microcirculatory failure in sepsis.
One week it's EBV, the next it's shingles, then it's stress or smoking. We need to step back and see the forest from the trees...
i would gladly have donated his "body parts" to science while we were going through the divorce.
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