Nerve Growth Potential of FK 506 and Its Analogues – A Systematic review of Controlled Trials in Rats
Bibliographic record
Abstract
Background Nerve injuries of the upper extremity seldom regain full preinjury function. Delay in nerve repair, nerve gap and ischemic local conditions are some of the factors attributed as the cause. The proximal axonal segment regenerates in the presence of neuronotrophic factors present in nerve tissue. FK 506 and its nonimmunosuppressive analogues have been shown to influence the growth of axons experimentally. Parallel studies of animals and human beings have demonstrated strong, toxic effects of these agents. Purpose To review systematically data on the role of FK 506 and its analogues in peripheral nerve regeneration of randomized, controlled trials in rats. Reports dealing with the toxic effects of these agents all were reviewed as well. Methods Articles and reviews were identified through a computerized search of MEDLINE from January 1966 to September 1999 by using the terms “FK 506”, “FKBP-12 ligands”, “peripheral nerve regeneration” and “nephrotoxicity, cardiotoxicity and neurotoxicity in FK 506”. Two reviewers assessed the trials independently. Results FK 506 caused dose-related enhancement of axonal growth in all animals that were tested and for all routes of drug administration. Effects of FK 506 when used locally and of its analogues occurred in the same order as those of the parent drug. Conclusions FK 506 and its analogues have been experimentally proven to be potent nerve stimulators. Further studies are warranted in view of the pathological and clinical potential for nephrotoxicity and cardiotoxicity of these agents. The authors proposed an experimental model incorporating a nerve conduit filled with slow release FK 506 at the site of nerve gap or crush, thus decreasing its systemic effects.
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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 | 0.006 | 0.016 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.005 |
| Bibliometrics | 0.008 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".