Demonstration of the direct impact of ketamine on urothelium using a tissue engineered bladder model
Bibliographic record
Abstract
INTRODUCTION: Ketamine is a common recreational drug. Severe lower urinary tract symptoms associated with its consumption have been reported, but little is known about the involved mechanisms. The effect of ketamine, which is excreted in urine, was evaluated by its application on an in vitro three-dimensional human tissue-engineered bladder model composed of an urothelium and a submucosa. METHODS: Human urothelial cells were cultured with medium containing various concentrations of ketamine and harvested at different times to obtain growth curves. Using this model, specific activity of caspase-3 was measured to assess the level of apoptosis induced by ketamine. Finally, a human tissue-engineered bladder model was used. Urothelial cells were plated on a stromal layer made of dermal fibroblasts and incubated at the air/liquid interface to allow their differentiation. Ketamine was then put on the mature urothelium using paper or agarose vectors for 48 hours. RESULTS: The presence of ketamine increased cells' doubling times from 1.26 days for control to 1.38 days (p = 0.14) and 1.78 days (p < 0.01) for the 0.5 mM and 1.5 mM concentrations, respectively. 5 mM and 10 mM of ketamine led to decline in the major cell population. Exposure to 5 mM ketamine induced apoptosis, confirmed by a 2.5-fold increase in capase-3 specific activity from control (p = 0.03). The structure and cellular cohesion of the urothelium on the three-dimensional model, especially in the intermediate layers, were severely affected in a concentration dependant fashion with both vectors. CONCLUSION: The presence of ketamine in the bladder directly damages the urothelium through the induction of apoptosis.
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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 | 0.001 |
| 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".