Chronic COX Inhibition Reduces Diabetes-Induced Hyperfiltration, Proteinuria, and Renal Pathological Markers in 36-Week B6-Ins2<sup>Akita</sup> Mice
Bibliographic record
Abstract
BACKGROUND/AIMS: The widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and the sizeable impact of diabetes on the development of end-stage renal disease substantiate the need to determine their effect on the evolution of diabetic nephropathy (DN). We hypothesized that chronic ibuprofen and NS-398 will differentially affect many aspects of DN in B6-Ins2(Akita) mice, including glomerular filtration rate (GFR), growth, and fibrosis. METHODS: B6-Ins2(Akita) and wild-type mice were separated into six groups. At 20 weeks of age, NSAIDs (1 mg/kg/day) were added to the drinking water daily. At 36 weeks indicators of renal function and DN were examined. RESULTS: Urinary PGE(2), PGEM, TXB(2), and 6-keto-PGF(1)alpha were increased in diabetics, and reduced by NSAIDs. Regional differences in cyclooxygenases were observed. Diabetics displayed hyperglycemia, albuminuria, and increased kidney/body weights, glomerular diameters, and FITC-inulin clearance. NSAIDs did not affect growth, but albuminuria and FITC-inulin clearance were reduced. Also, p27 and fibronectin were increased in diabetics and attenuated by ibuprofen. CONCLUSION: NSAIDs reduced diabetic change: GFR, albuminuria, p27, and fibronectin. The effects of ibuprofen are similar if not more beneficial than COX-2 inhibition by NS-398. This study has clinical relevance for diabetics prior to overt nephropathy. Future studies should reveal the effects of NSAIDs in a more severe disease environment.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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".