Bibliographic record
Abstract
Bi-directional transport studies on Caco-2 and MDCK monolayers showed that physico-chemical properties predicted both chelator and chelate transport across Caco-2 monolayers, but only predicted chelator---not chelate---transport across MDCK monolayers. Chelates are transported significantly faster in the apical-to-basolateral direction of MDCK monolayers. Chetator-induced iron removal was found preferentially from the basolateral membrane of iron-overloaded MDCK monolayers, and showed strong temperature-dependence. High plasma protein binding was found for ICL670 and its chelate, but not for the hydroxypyridinones (CP363, CP502 and deferiprone) or deferoxamine chelate. In the absence of iron overload, transferrin was found to shuttle iron from chelates of all hydroxypyridinones but not from ICL670 and deferoxamine. Iron chelators are effective at removing iron from the body in disorders of iron overload, but little is known about the process of iron excretion, notably the handling of iron chelates by the intestine and kidney, and the role of plasma proteins. We hypothesized that chelators and their iron chelates have independent biokinetic properties that determine the pattern of chelator availability and transmembrane flux of the iron chelate. We tested this hypothesis with monolayers of cells involved in intestinal (Caco-2) and renal (Madin-Darby canine kidney, MDCK) transport. The plasma protein binding of chelators and their chelates was evaluated to comprehend how this might affect their biokinetics. In summary, distinct differences were exhibited by iron chelators and their chelates in transport studies using intestinal and kidney membrane cell models. The polarized transport of iron chelates across MDCK monolayers together with the preferential iron efflux from the basolateral membrane provide the first evidence that the kidney may play an important role in reabsorption of iron bound to chelators. Further research directed at finding the relevant transporter and the reasons for its selectivity among chelators is warranted. The distinctive plasma protein binding characteristics of iron chelates from different chelators further furnish evidence that there is a need for studying chelate properties during chelator development.
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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 | 0.000 |
| 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) | 0.001 | 0.001 |
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".