FLUSH OR NEW THERAPEUTIC OPTIONS
Bibliographic record
Abstract
Introduction: The endocannabinoid system (ECS) consists of the cannabinoid receptors 1 (CB1) and 2 (CB2), endogenous ligands (lipids) and endocannabinoid-degrading mechanisms. To date the best characterized endogenous cannabinoids are anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG). Both act as agonists on CB1 and CB2 receptors. Several studies suggest that activation of the ECS results in anti-inflammatory effects. Aims: Aim of our study was to study possible anti-inflammatory effects in an experimental model of acute pancreatitis. Methods: Pancreatitis was induced by six hourly intraperitoneal injections of cerulein (50μg/kg bw) in wild-type C57/bl and CB1 −/− mice. HU210, a synthetic and specific CB1 agonist, or AM 281, a specific CB1 receptor antagonist, was administered 30 min prior to the first cerulein injection. Severity of pancreatitis was determined measuring serum amylase, IL-6 levels, trypsinogen activation, MPO activity and histological examinations. Pancreatic lysates were investigated by western blotting using phospho specific antibodies against p38 and JNK. Results: Administration of a single dose of HU210 significantly ameliorates the degree of pancreatitis showing reduced serum amylase, IL-6 levels, trypsinogen activation and improved histology. These protective effects were abolished by co-administration of the CB1 antagonist AM281. Administration of cerulein in CB1 −/− mice revealed the same degree of pancreatitis as in C57/bl wild-type mice, whereas administration of HU210 in CB1 −/− had no effect. Western blot analysis of p38 showed no significant differences in HU210 treated animals compared to cerulein-only treatment, while HU210 treatment resulted in decreased JNK-activation. Conclusion: Cannabinoids protect against cerulein-induced pancreatitis. The CB1 receptor plays an important role in the mediation of the protective effects. We furthermore show that the CB1 mediated anti-inflammatory effects comprise inhibition of JNK signaling in pancreatic acini.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.004 |
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; both teacher heads agree on what is shown here.
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".