Effect of Fingolimod on an animal surgical wound healing model: a non-immunosupressive profile. (P1.160)
Bibliographic record
Abstract
OBJECTIVE: Fingolimod is the first oral compound approved in the US, Canada and the EU for the treatment of Relapsing Remitting Multiple Sclerosis (RRMS). Inducing a S1P1 down-regulation that prevents lymphocyte egress from lymphoid tissues, it is considered an immunosuppressive agent. We used a well-defined experimental model to assess Fingolimod effects on cutaneous wound healing, a physiological process that involves neutrophils, lymphocytes and macrophages. BACKGROUND: Immunosuppressants are known to interfere with surgical wound healing. This is the case of Azathioprine, another oral drug labeled in Spain to treat RRMS. The increasing use of immunosuppressive drugs in MS warrants a better understanding of their effects on wound healing. DESIGN/METHODS: Forty-two Sprague-Dawley rats received Fingolimod 0.3 mg/kg/day (n=14), Azathioprine 1.5mg/kg/day (n=14) or sham (n=14) for 6 weeks before a 2 cm linear dorsal surgical wound closed with surgical staples was performed. Animals were still receiving treatment for 7 (n=21) and 21 (n=21) more days, until sacrifice, when surgical site tissue was collected and analyzed for optic microscopy (Masson´s tricromic), macrophage cell number (ED1) and collagen fiber content (Sirius red). Mass spectrometry was performed before surgery to confirm serum Fingolimod presence. The study followed the recommendations of the Guide for the Care and Use of Laboratory Animals of the National and European Institutes of Health. RESULTS: On day 7, Azathioprine provoked macroscopical disruption of the scar in 5/7 rats, compared to only 2/7 in the Fingolimod treated animals. Moreover, Macrophage content was lower in Azathioprine compared to Fingolimod and sham treated groups. No difference between the three groups on collagen formation was observed on day 7, but on day 21, Azathioprine group showed less collagen content. CONCLUSIONS: Compared to Azathioprine, Fingolimod does not interfere with wound healing. Tissue repair was not delayed and is similar to the pattern observed in sham treated rats.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.001 |
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".