Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstruction
Bibliographic record
Abstract
REASONS FOR PERFORMING STUDY: It has been suggested that many of the beneficial effects of corticosteroids are mediated through mitogen-activated protein kinase (MAPK) p38 inhibition. OBJECTIVE: To investigate the efficacy of the MAPK p38 inhibitor compound MRL-EQ1 to either prevent (Phase 1) or treat (Phase 2) recurrent airway obstruction (RAO) in horses. METHODS: MRL-EQ1 was administered i.v. at a dosage of 0.75-1.5 mg/kg bwt q. 12 h. In Phase 1, susceptible horses in clinical remission were divided into 2 groups (n = 5/group), based on historical values of respiratory mechanics. All horses were entered in the study in pairs (one control, one treated horse) and exposed to the same environmental challenge (stabling, mouldy hay and dusty conditions). The treatment group received MRL-EQ1 for 14 days while the control horses were untreated during the same period. In Phase 2, affected horses were ranked by severity of respiratory dysfunction and split randomly into either dexamethasone or MRL-EQ1 treatment groups (n = 5/group). Bronchoalveolar lavage fluid, respiratory mechanic measurements, MRL-EQ1 plasma concentration and tumour necrosis factor (TNF) whole blood activity were evaluated sequentially. RESULTS: In Phase 1, MRL-EQ1 did not prevent the occurrence of clinical signs and pulmonary inflammation. However, treatment was associated with a reduction in severity and a delay in the onset of signs and a reduction in pulmonary neutrophilia. In Phase 2, plasma concentrations achieved resulted in ex vivo suppression of lipopolysaccharide-induced TNF production in equine blood. MRL-EQ1 did not improve airway inflammation or lung function and was associated in a dose dependent manner with behavioural (depression, excitability) and blood changes (neutrophilia, increased serum muscle enzyme concentrations). CONCLUSIONS: Inhibition of p38 in the horse was partially effective in reducing clinical signs and airway inflammation when administered prior to, but not during clinical exacerbation in RAO. POTENTIAL RELEVANCE: Inhibitors of p38 MAPK with a better toxicity profile may be effective in the prevention or treatment of RAO.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".