Late intervention with a myeloperoxidase inhibitor prevents emphysema and small airway remodeling in the guinea pig
Bibliographic record
Abstract
Considerable evidence links both inflammation and oxidative stress to the pathogenesis of COPD. Myeloperoxidase (MPO), a neutrophil product, plays a major role in bacterial killing via production of the powerful oxidant, HOCl. However, oxidants generated by MPO can damage tissue and MPO exerts a variety of other effects that drive inflammation. We examined the effects of an MPO inhibitor, AZ11938920 on chronic (6 month) cigarette smoke-induced lesions in the guinea pig. One group of animals received compound from smoking day 1 (prophylactic arm), whereas another group was only treated after 3 months of smoke exposure (therapeutic arm). Analysis of lavage fluid showed that both treatments abolished smoke-induced increases in lavage inflammatory cells. Both treatments prevented smoke-induced increases in airspace size (emphysema) and small airway remodeling. Physiologically, both treatments largely reversed smoke-induced shifts of the pressure-volume and flow-volume curves and returned resistance to control values. Both treatments prevented muscularization of the small intrapulmonary arteries, but only partially ameliorated smoke-induced pulmonary hypertension. Immunohistochemical staining for the oxidation product, dityrosine, was increased in smoke-exposed animals and this effect was largely reversed by both treatments. We conclude that a myeloperoxidase inhibitor is able to prevent the development of emphysema and small airway remodeling and to partially protect against pulmonary hypertension, even when treatment starts after 3 months of smoke exposure. This protection appears to be related to prevention of oxidant damage and suppression of inflammation.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".