PIII-46Generation of reactive oxygen species by sulfonamide reactive intermediates
Bibliographic record
Abstract
BACKGROUND/AIMS Reactive sulfonamide intermediates appear to be key elements in the pathogenesis of sulfonamide hypersensitivity reactions. The molecular mechanism(s) driving this remains unclear. Reactive stress may be involved in undesired effects of reactive compounds; thus we studied the generation of reactive oxygen species by sulfonamide reactive intermediates. METHODS Design _ An in vitro study using Jurkat cells incubated with increasing concentrations of the hydroxylamine metabolite of sulfamethoxazole over increasing incubation times. Toxicity was evaluated by MTT assay and FACS analysis. Reactive oxygen stress was determined with a colorometric assay with DCFH-DA as an indicator. Setting _ Lab. Targets _Jurkat E6-1 cells. Intervention _ Incubation of cells with a reactive intermediate of sulfamethoxazole from 0 to 800 micromolar. The metabolite was synthesized using our previously described method. RESULTS Concentration and time dependent increases in reactive oxygen stress were demonstrated when cells were incubated with the hydroxylamine of sulfamethoxazole but not with the parent drug or vehicle control. The increase was statistically significant for all concentrations above 100 micromolar (p<0.05). At the 800 micromolar concentration, the increase was 700-fold (p<0.01). CONCLUSIONS Reactive oxygen stress may be an important molecular determinant of sulfonamide hypersensitivity and thus interventions to reduce or reverse this may be therapeutic options. Clinical Pharmacology & Therapeutics (2005) 79, P70–P70; doi: 10.1016/j.clpt.2005.12.254
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".