Long‐term immunosuppression of rabbits through oral tacrolimus administration
Bibliographic record
Abstract
BACKGROUND: The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments. Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits. However, determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging. METHODS: In this study, we investigated the effect of orally administered tacrolimus in rabbits, with an aim to achieve a whole blood target trough level of 3-10 ng/mL, and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve. An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits. RESULTS: We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression, with side effects mainly limited to diarrhea. Customizing the administered dose proved crucial for graft efficacy and low toxicity, which translated into 100% individual survival. We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/mL, as levels below 5 ng/mL showed signs of inflammation in the graft. CONCLUSION: The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 |
| 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".