Circular dichroism study of interactions of Fungizone or AmBisome forms of amphotericin B with human low density lipoproteins
Bibliographic record
Abstract
Amphotericin B (AmB), a potent antifungal agent used to treat invasive fungal infections, is still employed more than 40 years after its introduction in the pharmacopea. When injected into the blood stream, this antibiotic is carried by low density lipoproteins (LDLs) to which it induces the formation of oxidation products responsible in part for some of the severe adverse effects of the drug. However, the oxidative damages induced to LDLs are not yet understood. We present here the effects of the Fungizone and AmBisome forms of AmB on LDLs as compared to those of CuSO(4), a well-known powerful oxidant of LDLs. We use circular dichroism (CD) spectroscopy, which is particularly useful because it allows the investigation of the structural integrity of the proteic moiety of LDL upon interaction with AmB. The CD spectra also yield information on the drug itself because in its oligomer form it presents a strong dichroic signal in a spectral region different from that of the protein. Our results show that neither form of AmB changes the secondary structure of the protein while the helical content of the LDL is increased either in the presence of CuSO(4) alone or in the presence of CuSO(4) and AmBisome or Fungizone. On the other hand, the CD spectra of the antibiotic indicate that Fungizone AmB suffers important oxidative damage in the presence of LDLs and CuSO(4) while this damage is not present with AmBisome AmB. These observations lead us to propose that the structural modifications of the proteic part of LDLs induced by the Cu(2+) ions are involved in the important oxidative damage suffered by Fungizone AmB, which in this form is much more susceptible to interaction with its environment than AmBisome.
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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 | 0.000 |
| 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) | 0.000 | 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".