Therapeutic options in inflammatory bowel disease: experimental evidence of a beneficial effect of kinin B<sub>1</sub> receptor blockade
Bibliographic record
Abstract
A surprising proportion of patients with inflammatory bowel disease (IBD) remain refractory to all classes of drugs presently in clinical use. Kinins are inflammatory mediators of potential relevance in IBD, because at least the kinin B1 receptor subtype is upregulated in human or animal intestinal inflammation and also both B1 and B2 receptors for kinins support inflammation and epithelial electrogenic ion transport that leads to secretory diarrhoea. In this issue of the BJP, Hara et al. report the therapeutic effect of a modern and selective nonpeptide kinin B1 receptor antagonist, SSR240612 ((2R)-2-(((3R)-3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulphonyl)amino)propanoyl)amino)-3-(4-((2R,6S)-2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide hydrochloride), with benefits such as decreased neutrophil influx and improved macroscopic tissue scoring. The results were corroborated using kinin B1 receptor gene-knockout mice. Further, kinin B1 receptor upregulation in this inflammatory model is partially dependent on TNF-alpha, a recognized target for IBD pharmacotherapy. More work is warranted to evaluate the value of the kinin B1 receptor antagonists as a novel anti-inflammatory therapeutic option for IBD.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".