Mode of Action: Angiotensin-Converting Enzyme Inhibition—Developmental Effects Associated With Exposure to ACE Inhibitors
Bibliographic record
Abstract
Relative to species tested in laboratory studies, the human fetus displays higher vulnerability to enalapril and other angiotensin-converting enzyme inhibitors (ACEI) exhibiting a malformative syndrome that does not appear to have a similar counterpart in experimental animals. An important reason for this higher vulnerability is the earlier intrauterine development of the kidney and the renin-angiotensin-aldosterone (RAS) system in humans, organ systems that are specific targets of ACEI's pharmacological effect. In humans, these systems begin developing prior to the onset of skeletal ossification at the end of the first trimester, with continuing vulnerability throughout the pregnancy. In most animal species tested, these target systems develop close to term, when the fetus is relatively more mature and less vulnerable to the effects of developmental toxicants. For this reason, animal studies that follow standard protocols and evaluate developmental toxicity only for exposures during embryogenesis will miss developmental effects arising secondary to disruption of target systems that develop after the period of major organogenesis. Thus, although the animal mode of action (MOA) for enalapril and other ACEI is plausible in humans, differences in the timing of development of critical target organ systems, particularly the renal system and RAS, explain the absence of definitive structural abnormalities in test animals.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".