Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-<i>cy</i>rat kidneys
Bibliographic record
Abstract
Renal prostanoids are important regulators of normal renal function and maintenance of renal homeostasis. In diseased kidneys, renal cylooxygenase (COX) expression and prostanoid formation are altered. With the use of the Han:Sprague-Dawley-cy rat, the aim of this study was to determine the relative contribution of renal COX isoforms (protein, gene expression, and activity) on renal prostanoid production [thromboxane B(2) (TXB(2), stable metabolite of TXA(2)), prostaglandin E(2) (PGE(2)), and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha), stable metabolite of PGI(2))] in normal and diseased kidneys. In diseased kidneys, COX-1-immunoreactive protein and mRNA levels were higher and COX-2 levels were lower compared with normal kidneys. In contrast, COX activities were higher in diseased compared with normal kidneys for both COX-1 [0.05 +/- 0.02 vs. 0.45 +/- 0.11 ng prostanoids x min(-1) x mg protein(-1) (P < 0.001)] and COX-2 [0.64 +/- 0.10 vs. 2.32 +/- 0.22 ng prostanoids x min(-1).mg protein(-1) (P < 0.001)]. As the relative difference in activity was greater for COX-1, the ratio of COX-1/COX-2 was higher in diseased compared with normal kidneys, although the predominant activity was still due to the COX-2 isoform in both genotypes. Endogenous and steady-state in vitro levels of prostanoids were approximately 2-10 times higher in diseased compared with normal kidneys. The differences between normal and diseased kidney prostanoids were in the order of TXB(2) > 6-keto-PGF(1alpha) > PGE(2), as determined by higher renal prostanoid levels and COX activity ratios of TXB(2)/6-keto-PGF(1alpha), TXB(2)/PGE(2), and 6-keto-PGF(1alpha)/PGE(2). This specificity in both the COX isoform type and for the prostanoids produced has implications for normal and diseased kidneys in treatments involving selective inhibition of COX isoforms.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".