Evaluation of Carbon Monoxide as a Therapeutic for Preeclampsia
Bibliographic record
Abstract
Preeclampsia (PE), a hypertensive complication of pregnancy, is one of the leading causes of maternal and neonatal morbidity and mortality. The etiology of PE is not well-understood, however it is widely accepted to occur in two stages: poor uteroplacental perfusion and placental ischemia, which subsequently leads to a systemic maternal inflammatory response and multi-organ effects. Although cigarette smoking during pregnancy is known to cause aberrant placental development and adverse pregnancy outcomes, smoking reduces the risk of PE by 33% in a dose-dependent manner. The same risk reduction does not hold true for users of smokeless tobacco products. This has lead to the notion that carbon monoxide (CO), one of the byproducts of cigarette combustion, may confer this decrease in PE risk. Endogenously, CO is produced through the degradation of heme by heme oxygenase (HO), and it has been suggested that modulation of the HO/CO system may attenuate the development or progression of PE. The studies presented herein demonstrate that low doses of CO, delivered through gaseous CO or CO donor molecules, may exhibit physiological benefits and have therapeutic potential during complicated pregnancies. Firstly, the challenges associated with reproducing the AdsFlt-1-induced mouse model of PE for studying the effects of CO in complicated pregnancies were investigated. Clinically, inhaled CO was shown to moderately increase biological CO above endogenous levels, and increase vascular responses in the cutaneous microvasculature. In mice, it is demonstrated that the CO-releasing molecule (CORM-A1) is able to transiently increase biological CO levels. CORM-A1 delivered in mid-gestation, resulted in increased CO, without adverse maternal or fetal effects, indicating the potential for CORM-A1 as a novel method to deliver CO during pregnancy. Collectively, the data presented in this thesis verify that low dose CO may have therapeutic properties to improve endothelial dysfunction, increase placental perfusion, and reduce progression of the clinical signs of PE.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".