A Rapid and Sustained Increase in Neutrophil Elastase Levels Correlates Temporally with Decreased Coagulation Factor Activity during E.coli-Sepsis in Baboons.
Bibliographic record
Abstract
Abstract Infection is the most common pathology resulting in disseminated intravascular coagulation (DIC) in humans. Disturbances of the cell interactions between neutrophils and endothelial cells are an integral part of the pathophysiology of E.coli-sepsis. Although neutrophil elastase (NE) is required for the destruction of gram negative bacteria, dysregulated NE activity towards coagulation factors may contribute to the coagulopathies that accompany infections if its activity is not properly regulated by alpha-1-protease inhibitor (A1PI). The temporal relationships between these variables were studied in plasma samples from three baboons before and after infusion of either two sublethal doses (2.50x106 cfu/kg and 1.10x108 cfu/kg) or a lethal dose (6.50x108 cfu/kg) of E.coli. In comparison to pre-infusion levels, the A1PI/NE complex levels increased by up to 17-fold after 2hrs and remained 6-fold above baseline after 53hrs as the amount of E.coli was increased. In contrast, the A1PI activity and specific activity both decreased by up to 30% during the 2–6hrs following the lethal dose of E.coli. Large transient decreases, of between 60–96%, in the factor V and VIII activity and fibrinogen levels occurred only during the 2–6hrs following infusion of the lethal dose. In addition, there was a 70–80% decrease in the factor II, VII, IX, and X clotting activity after 6–24hrs as the dose of E.coli was increased. In conclusion, there is a temporal association between the changes in A1PI activity, the appearance of the A1PI/NE complex, and the decrease of coagulation factor activity during E.coli-sepsis in baboons. Further, the sustained elevation of the A1PI/NE complexes beyond 48hrs, even after sublethal challenge with E.coli, indicates that a persistent increase in the neutrophil activity occurs as part of the inflammatory response to bacterial infection in this animal model. This study demonstrates that the neutrophil/endothelial interaction continues far beyond the first margination stage into the second ischemia/reperfusion stage during E.coli-sepsis. The results raise the possibility that clotting factor degradation/inactivation by NE as well as consumption via the coagulation cascade occurs following infusion of sublethal and lethal doses of E.coli.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".