Study of the Sequence of Events Involved in Nevirapine-Induced Skin Rash in Brown Norway Rats
Bibliographic record
Abstract
Nevirapine, used for the treatment of HIV infection, is associated with development of skin rash and liver toxicity. The mechanism of these idiosyncratic reactions is unknown. We have previously reported the discovery of a new animal model of nevirapine-induced skin rash in rats. When treated with nevirapine, Brown Norway rats developed red ears on about day 7 and skin rash on about day 21. On rechallenge, ears turn red within 24 h, and skin lesions develop by day 9. In the current study, we analyzed the time course of the sequence of events involved in the development of skin rash. Rats were treated with nevirapine for 7, 14, or 21 days or rechallenged with it for 0, 1, or 9 days. This treatment led to an increase in the total number of auricular lymph node T, B, and macrophage cells. There was also an increase in the activation/infiltration marker ICAM-1 and activation/antigen presentation marker MHC II in these cells compared with those from control rats. Immunohistochemistry analysis showed macrophage infiltration and ICAM-1 expression in the ears of treated rats as early as day 7 of treatment. Macrophage infiltration preceded T cell infiltration, which was not apparent until the onset of rash. Both MHC I and MHC II expression increased in the skin of nevirapine-treated rats that developed rash. A major inducer of MHC is IFNgamma. Although rechallenge with nevirapine led to a large increase in serum levels of IFNgamma, this was not observed during the treatment of naïve rats with nevirapine. These observations provide further clues to the mechanism of nevirapine-induced skin rash.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".