Elimination of vascular fibrointimal hyperplasia bysomatostatin receptor 1.4 selective agonist
Bibliographic record
Abstract
The somatostatin analogs octreotide and lanreotide, selective to receptor subtypes 2 and 5, failed clinical efficacy for the prevention of restenosis after percutaneous transluminal angioplasty. These findings might have been the result of targeting a wrong subset of receptors. In rat arteries, subtypes 1 and 4 are expressed 3-4 times more prominently than 2 and 5, and subtype 1 is the nearly exclusive subtype in atherosclerotic human vessels. Here, we demonstrate that daily s.c. injections (50-500 microg/kg/d) of CH275 (DesAA1,2,5(D-W8,IAmp9)Somatostatine-14), selective to subtypes 1 and 4, dose-dependently inhibited intimal hyperplasia 14 days after rat carotid denudation injury (for intimal area P=0.0002 across the dose range). CH275 was more effective than somatostatin-14 (equal affinity to all five subtypes, P=0.03), or octreotide (selective to subtypes 2 and 5, P=0.098). When rats were given the peptides for 14 days with end-point at 28 days, CH275 still significantly inhibited intimal area expansion. Both CH275 and octreotide inhibited the outgrowth of cells from postinjury aortic tissue punch-explants and the distance migrated in vitro, but not cell replication, which indicated that the effects of somatostatin analogs were directed on the migration of intimal cell progenitors rather than on their proliferation.
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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 | 0.000 | 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 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".