A Hydrogen‐Sulfide Releasing Derivative of Mesalamine Exhibits Markedly Enhanced Anti‐Inflammatory Effects in Experimental Colitis
Bibliographic record
Abstract
Colitis is characterized by mucosal injury, transepithelial leukocyte migration and mucosal inflammation. Hydrogen sulfide (H2S) has recently been shown to play an important role in mucosal defence and in suppressing leukocyte infiltration. We have synthesized an H2S‐releasing derivative of mesalamine (ATB‐429), the first‐line therapy for IBD, and have tested the hypothesis that it would exhibit enhanced anti‐inflammatory effects in experimental colitis. The mouse TNBS‐ colitis model was used. Groups of mice were orally treated with mesalamine or ATB‐429 (25–75 mg/kg) daily for 7 days. Mucosal injury and inflammation was then assessed. ATB‐429 exhibited an increase in potency and a broadening of efficacy as compared to mesalamine in TNBS‐induced colitis. ATB‐429 was more effective than mesalamine in reducing the severity of colitis, and in reducing granulocyte infiltration and mucosal expression of mRNA for TNF, IFNã, IL‐2, IL‐6, and RANTES (but not IL‐10). These effects of ATB‐429 may be attributable, at least in part, to its observed ability to suppress NF‐kB translocation. These results demonstrate that the addition of an H2S‐releasing moiety to mesalamine resulted in a significant increase in potency, as well as a marked broadening of anti‐inflammatory effects. The inhibition of leukocyte infiltration of the mucosa may contribute to the enhanced repair of mucosal injury by ATB‐429. αα
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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".