Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart
Bibliographic record
Abstract
1. Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism. 2. The effect of interferon-induced acute inflammation on the pharmacokinetics and electrocardiogram of verapamil (20 mg kg(-1), p.o.) and nifedipine (0.1 mg kg(-1), i.v.) was studied in Sprague-Dawley rats. 3. The effect of both acute and chronic inflammation on radioligand binding to cardiac L-type calcium channels was also investigated. 4. Acute inflammation resulted in increased plasma concentration of verapamil but had no effect on that of nifedipine. Verapamil binding to plasma proteins was unaffected. 5. As has been reported for humans, the increased verapamil concentration coincided with a reduction in the degree to which PR interval is prolonged by the drug. The effect of nifedipine on PR interval was also reduced by inflammation. 6. Maximum binding of (3)H-nitrendipine to cardiac cell membrane was significantly reduced from 63.2+/-2.5 fmol mg(-1) protein in controls to 46.4+/-2.0 in acute inflammation and from 66.8+/-2.2 fmol mg(-1) protein in controls to 42.2+/-2.0 in chronic inflammation. 7. Incubation of the normal cardiac cell membranes with 100 and 1000 pg ml(-1) of rat tissue necrosis factor-alpha did not influence the binding indices to the calcium channels. 8. Our data suggest that the reduced calcium channel responsiveness is because of altered binding to channels.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".