Enhanced anti‐inflammatory potency of a nitric oxide‐releasing prednisolone derivative in the rat
Bibliographic record
Abstract
1. Derivatization of nonsteroidal anti-inflammatory drugs, such that they release nitric oxide (NO) in small amounts, has been shown to significantly increase their anti-inflammatory activity and analgesic potency. In this study, we compared the anti-inflammatory potency of prednisolone to a nitric oxide-releasing derivative of prednisolone (NCX-1015). 2. Carrageenan-induced inflammation of an airpouch in the rat was used. The rats were pretreated with equimolar doses of prednisolone or NCX-1015 and the effects on leukocyte infiltration into the airpouch and exudates levels of prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)) and nitrite (as an index of NO production) were measured 6 h later. 3. Injection of carrageenan into the airpouch resulted in a progressive increase in leukocyte infiltration, and accumulation of PGE(2), LTB(4) and nitrite. Carrageenan also induced elevated expression of cyclooxygenase-1 and -2, inducible nitric oxide synthase and 5-lipoxygenase in the inflammatory exudate. 4. Prednisolone dose dependently reduced the numbers of leukocytes within the airpouch exudates, as well as reducing PGE(2), LTB(4) and nitrite levels. NCX-1015 also reduced leukocyte numbers and inflammatory mediator levels. However, the doses of NCX-1015 required to produce a maximal reduction of each of these parameters was one-third to one-tenth the dose of prednisolone that produced a comparable effect. 5. The reduction of PGE(2) and NO production was likely to be at least in part due to reduced expression of the key enzymes responsible for their synthesis (cyclooxygenase-2, inducible NO synthase), with NCX-1015 producing greater suppression than prednisolone at an equimolar dose. 6. Coadministration of prednisolone with a nitric oxide donor (DETA-NONOate) resulted in a greater reduction of leukocyte infiltration and inflammatory mediator production than was observed with either drug alone. 7. These results support the notion that delivery of NO to a site of inflammation can markedly enhance the anti-inflammatory activity of a glucocorticoid.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".