Cyclooxygenase‐2 contributes to dysmotility and enhanced excitability of myenteric AH neurones in the inflamed guinea pig distal colon
Bibliographic record
Abstract
We have previously demonstrated that trinitrobenzene sulphonic acid (TNBS)-induced colitis in guinea pig is associated with hyperexcitability of myenteric AH neurones, enhanced synaptic activity in the myenteric plexus, increased serotonin (5-HT) availability in the mucosa, and decreased propulsive motor activity. The current study tested the hypothesis that the activation of cyclooxygenase (COX) contributes to these alterations in bowel functions. DFU inhibition of COX-2, but not SC-560 inhibition of COX-1, restored to normal levels the electrical properties of myenteric AH neurones, the proportion of S neurones exhibiting slow EPSPs, and the rate of propulsive motor activity. Neither inhibitor was effective in altering the level of inflammation, the increased availability of mucosal 5-HT, or the enhanced fast EPSPs in myenteric AH and S neurones. COX-2 expression is enhanced in the myenteric plexus and cells within the smooth muscle layers during colitis, possibly reflecting the site at which COX-2 inhibition acts to allow recovery of motor function. In support of this concept, COX-1, but not COX-2, inhibition was effective in restoring normal mucosal prostaglandin levels. These results indicate that the various changes that occur in the motor neural pathways of the distal colon in TNBS-induced colitis do not involve a single neuroimmune mechanism. COX-2 activation is a critical step in the enhanced excitability of AH neurones as well as diminished propulsive motility in TNBS colitis, whereas other yet to be resolved pathways, that do not involve COX-1 or COX-2 activation, lead to altered 5-HT content in the mucosa and an augmentation of fast EPSPs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".