Effect of Bosentan on Plasma Markers of Endothelial Cell Activity in Patients with Secondary Pulmonary Hypertension Related to Connective Tissue Diseases
Bibliographic record
Abstract
OBJECTIVE: To evaluate plasma markers of endothelial cell activity in patients with pulmonary arterial hypertension (PAH) induced by connective tissue diseases (CTD) before and after 3-month administration of bosentan. METHODS: We quantified E, L and P-selectin (sE-S, sL-S, sP-S), thrombomodulin (TM), monocyte-chemotactic protein 1 (MCP-1), human soluble CD40 ligand (sCD40L), and nitric oxide (NO) in 18 patients and 18 controls. We evaluated right ventricular systolic pressure (RVSP) and the 6-minute walk test (6-MWT). RESULTS: All plasma markers but sL-S and TM at Time 0 were significantly higher in patients compared with controls. After 3 months of therapy, decreased levels were noted in NO (Time 0 24.05+/-6.01 mmol/l, Time 1 13.92+/-3.40 mmol/l; p<0.001) and sCD40L (Time 0 1685.33+/-866 pg/ml, Time 1 1055.11+/-630.6 pg/ml; p=0.017). In contrast, sP-S was significantly increased (Time 0 88.36+/-47.76 ng/ml, Time 1 147.21+/-94.43 ng/ml; p=0.021). All patients remained stable in WHO class III, and in 9 patients we noted an improvement in 6-MWT. A correlation was found between Delta of RVSP and 6-MWT (r2=0.5355, p<0.001) as well as between Delta-sP-S and both Delta-6-MWT and Delta-RVSP. An increase sP-S level was found in 89% of nonresponder patients, whereas 55% of responders showed a stable or reduced sP-S level (p=0.016 responder vs nonresponder). CONCLUSION: Treatment with bosentan for 3 months induced a beneficial effect by restoring endothelial function through a decrease in the markers of endothelial cell activity, leading to stabilization or improvement of severe PAH.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 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".