Evaluation of Pefabloc as a serine protease inhibitor during human-islet isolation
Bibliographic record
Abstract
BACKGROUND: Recent evidence has suggested that inconsistencies in human-islet yields after collagenase digestion are attributed to the activation of endogenous enzymes of the cadaveric donor pancreas. Inhibition of protease activity by Pefabloc (0.4 mM; Roche Biochemicals Inc., Indianapolis, IN) has recently been shown to improve human-islet isolation after prolonged cold storage of the pancreas. In this study, we have hypothesized that this improvement was because of the inhibition of three key serine proteases. METHODS: Twenty cadaveric pancreases were perfused in the presence (n=12) and absence (n=8) of Pefabloc added at the time of distention using a customized perfusion device. Samples were collected throughout the digestion process and were assayed for trypsin, chymotrypsin, elastase, and total protease activity. RESULTS: In all cases, the enzyme activity levels remained lower in the presence of Pefabloc as compared with the control samples. There was significantly higher chymotrypsin and elastase activity in the control group, but not trypsin or total protease activity, from the time following loading of the enzyme onto the pancreas until the stopping of the enzymatic digestion phase (dilution). CONCLUSIONS: Pefabloc was shown to be an effective protease inhibitor throughout the entire digestion process. Pefabloc supplementation did not significantly effect the dilution time or the islet yield in this study; however, these data show that serine proteases are effectively inhibited by Pefabloc during the clinical islet process.
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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) | 0.000 | 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) | 0.001 | 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".