Phosphoramidon treatment improves the consequences of chagasic heart disease in mice
Bibliographic record
Abstract
Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is an important cause of cardiomyopathy. Microvascular spasm and matrix dissolution, modulated by endothelin-1 (ET-1), is implicated in the pathogenesis of chagasic heart disease. To further elucidate the role of ET-1 in murine chagasic heart disease, C57BL/6 x 129sv mice were infected with T. cruzi (10(3) trypomastigotes of the Brazil strain). These mice are resistant to death during the acute phase but progress to chronic cardiomyopathy. Infected mice were compared with infected mice treated with phosphoramidon, a non-specific metalloprotease inhibitor that is also a potent inhibitor of endothelin-converting enzyme, at a dose of 10 mg/kg. Mice were treated with phosphoramidon for the initial 15 days post infection (PI). All mice were evaluated 200 days PI. Examination of infected, untreated mice revealed marked inflammation, vasculitis and fibrosis. The hearts of infected treated mice had significantly less pathology. Cardiac magnetic resonance imaging (MRI) revealed that right ventricular internal diameter (RVID) was significantly greater (P<0.05) in the infected untreated group (2.9+/-0.22 mm) as compared with the infected treated group (1.73+/-0.35 mm). In another experiment phosphoramidon treatment was also tested in CD1 mice, which have a high mortality during the acute phase of infection with 5 x 10(4) trypomastigotes of the Brazil strain. One group of CD1 mice was untreated while the other group received phosphoramidon for the initial 15 days PI. The mortality rate in untreated mice was 70% by day 35 PI, while all treated infected mice lived. The parasitemia in both groups was similar. The cardiac pathology was more severe in untreated mice. MRI revealed the RVID to be significantly greater in the untreated infected group as compared with the phosphoramidon-treated infected mice (2.74+/-0.03 mm versus 1.64+/-0.4 mm P<0.05). Transthoracic echocardiography revealed that the percentage fractional shortening was reduced in infected CD1 mice but not in those infected mice treated with phosphoramidon. There was no effect of phosphoramidon in uninfected mice. Phosphoramidon (100 microg/ml) had no effect on parasites in vitro. These data are consistent with the hypothesis that ET-1 contributes to the pathogenesis of murine chagasic cardiomyopathy and suggests that interventions targeting ET-1 would improve the outcome in chagasic heart disease.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".