Role of the Tie2 agonist Vasculotide in murine Staphylococcus aureus pneumonia
Bibliographic record
Abstract
Introduction Community acquired pneumonia (CAP) is a significant cause of mortality worldwide. Despite adequate antibiotic treatment, severe pneumonia may induce pulmonary endothelial inflammation and hyperpermeability, resulting in life threatening lung failure. Compared to Streptococcus pneumoniae Staphylococcus aureus (S.a.) is a less common pathogen in CAP, but associated with a severe course of disease and a high mortality rate. Angiopoietin-1 (Ang-1) mediated Tie2-receptor activation reduces inflammation and stabilizes lung endothelial barrier. We have recently shown that the PEGylated (polyethylene glycol) Ang-1 mimic Vasculotide (VT) reduces lung hyperpermeability in murine pneumococcal pneumonia. The aim of our study was to investigate the influence of VT in an in vivo model of S.a. infected mice. Methods Pulmonary hyperpermeability, immune cell response and bacterial load were quantified in S.a. (1x108 CFU) infected mice (C57BL/6N) treated with VT (500 ng/100 µl) or PBS (100 µl) in a 12 h interval, starting 10 h post infection (p.i.). Additionally, body weight and body temperature measurements were conducted. Preparation, bronchoalveolar lavage (BAL) and analysis were performed at 12 h, 24 h and 48 h p.i. Human serum albumin (HSA; 1 mg/75 µl) was intravenously injected 1 h before preparation to quantify endothelial permeability using HSA-BAL-fluid/plasma ratio. Results Clinical parameters like body weight and body temperature were not affected by VT treatment. There was a tendency towards reduction in pulmonary permeability 24 h p.i. in the VT treated group in comparison to control group, however reduction was not significant. VT did not demonstrate an impact on pulmonary or systemic leucocytes count or bacterial load. Conclusions Present results may indicate that VT stabilizes pulmonary barrier function without impacting immune response in murine S.a. pneumonia, similar to its effects observed in murine pneumococcal pneumonia. However, more detailed investigations are necessary in upcoming experiments. Publication History Article published online: 11 May 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany
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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 | 0.000 |
| 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".