The polycationic aminoglycosides modulate the vasoconstrictive effects of endothelin: relevance to cerebral vasospasm
Bibliographic record
Abstract
1. The vasoactive peptide endothelin (ET) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid haemorrhage. In these studies we investigated the involvement of protein kinase C (PKC) in sustained vasoconstriction induced by ET-1 in canine cerebral arteries. We also examined the ability of the aminoglycoside antibiotics to reverse the effects mediated by ET-1 in canine cerebrovascular smooth muscle cells (CVSMC). 2. The ET(A) receptor antagonist, BQ-123, showed a competitive inhibition of the ET-1 responses. 3. The vasoconstrictor action of both ET-1 (0.5 nM) and phorbol myristate acetate (PMA) (160 nM) was reversed by a selective PKC inhibitor, Ro-32-0432. 4. In cerebral arteries precontracted with ET-1 the aminoglycosides caused a concentration-dependent relaxation. The EC(50s) for the relaxation were as follows: 0.54+/-0.05, 0.63+/-0.01, 1.88+/-0.46 and 2.3+/-0.92 mM for gentamicin, neomycin, streptomycin and kanamycin, respectively. 5. Gentamicin caused a concentration-dependent decrease of the PMA-induced responses in calcium free medium. 6. PKC activity was elevated in CVSMC exposed to ET-1 (170%) and PMA (167%) for a period of time (60 min) corresponding to maximum tonic contraction induced by these agents in arterial rings. 7. The administration of the aminoglycosides to CVSMC, in concentrations corresponding to the EC(50s) from contractility studies, reduced the effects of both ET-1 and PMA on PKC activity to the levels not different from controls. 8. These results show that the aminoglycosides are able to inhibit sustained vasoconstriction induced by ET-1, an effect which is due, at least in part, to the inhibition of PKC.
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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) | 0.001 | 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 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".