A270 EFFECTS OF KETOPROFEN AND ITS HYDROGEN SULFIDE-RELEASING DERIVATIVE ON THE IMMATURE HUMAN INTESTINE
Bibliographic record
Abstract
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) among neonates is associated with a broad spectrum of life-threatening adverse effects on the gastrointestinal tract. Indeed, we have previously demonstrated that NSAIDs, such as indomethacin (INDO), induce damaging effects on the immature intestine (Perron et al. Genomics, 2013). Hydrogen sulfide (H2S) has been reported to exert a number of cytoprotective and anti-inflammatory effects in many organ systems. Thus, in order to minimize the deleterious effects caused by NSAIDs, several H2S-releasing derivatives have been developed, including ATB-352, an H2S-releasing derivative of ketoprofen. In the present study, we determined the effects of ketoprofen (KETO) and its H2S-releasing derivative on the human mid-gestational intestine using serum-free organ culture, and compared them with those previously described for INDO. The representative genes involved with the deleterious effect of INDO were used as reference to compare the effect of KETO and/or its derivative ATB-352 on the mid-gestation human small intestine after a treatment of 48 hours. Gene expression levels were measured by qRT-PCR. By determining the gene expression of COX2 in cultured human small intestinal explants, we observed two distinct patterns of response that allowed to divide the specimens into two groups: 1) those with an increased expression of COX2 mRNA (KETO-responder group), and 2) those where COX2 remained unchanged (non-responder group). For the non-responder group, no significant change was observed compared to control. Although the inflammatory response observed between INDO and the KETO-responder group was similar (CXCL14 and TFF1), the negative effects on oxidoreductase activity (DUOX2, NOS2, SOD2) and intestinal permeability (OCLN, CLDN1) induced by INDO were not found with KETO, suggesting a beneficial effect of KETO on the small intestinal mucosa. In addition, the use of the H2S-releasing derivative of KETO did not induce significant changes compared to KETO on these metabolic pathways. Our results show that KETO (responder group) has beneficial effects on oxidoreductase activity and epithelial permeability in the immature human small intestine compared to INDO. However, the lack of beneficial effects of H2S on the small intestinal mucosa in organ culture suggests a systemic type mechanism rather than a local one. CIHR
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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) | 0.002 | 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".