PREVENT ACUTE HUMORAL REJECTION BY A NOVEL IMMUNOSUPPRESSANT, PG490-88 IN A STRINGENT CANINE RENAL ALLTRANSPLANTATION MODEL
Bibliographic record
Abstract
A304 Aims: It is critical to develop new immmunosuppressant to prevent acute humoral rejection, the most awful clinical course in organ transplantation, and no agent is effective enough to handle it. PG490-88 is a water soluble, semisynthetic derivative of a novel compound PG490 (triptolide) purified from the Chinese herb Tripterygium Wilfordii Hook F. PG490-88 inhibits T cell proliferation in vitro and in vivo and prolongs cardiac and renal allograft survival in rodent models, even in xenotransplantation model. No immunosuppressive investigation of PG490-88 on large animal has been reported. In this study, we are going to evaluate the immunosuppressive effect of administrating PG490-88 alone or combined with FK506 orally in a stringent dog renal transplantation model, especially for prevention acute humoral rejection. Methods: All the male beagle dogs as the recipient and the donor were obtained from different breeders to ensure that the donor and the recipient were mismatched. PG490-88 and/or FK506 were administrated orally based on protocol design. The general condition, hematological and biochemical profiles were monitored. The animals were sacrificed when uremia developed or other complications. Full autopsies were performed to confirm cause of death. The routine histology was performed in each case, the immunohistochemical staining of the C4c, IgM, IgG, B-cell, and CD3 was performed in PG treated and combination groups Results: All the dogs in untreated untreated group developed acute humoral rejection with median survival time of 6 days, and the graft presented massive hemorrhage, IgM, IgG, and deposition. PG490-88 0.06 mg/kg/d treated group, prolonged graft survival with median survival time 11 days. (, P= 0.038 vs control). When this dose was combined with FK506 0.3 mg/kg/d treatment, it could further prolong the survival with median survival time 15 days. (P=0.017, vs control). Comparing to untreated control group, PG490-88 0.1 mg/kg/d treated group could not prolong the graft survival with median survival time 8.5 days due to the non-surgical complication. The pattern of acute humoral rejection was attenuated. C4c deposition significantly decreased in PG0.06, PG0.1, and combination group, even if the IgM, IgG and B-cell still deposited. FK506 0.3 mg/kg/d treated group could not prolong the graft survival with median survival time 10 days. FK506 0.06 mg/kg/d treated group prolonged the graft survival time with median survival time 24 days. (P =0.006 vs control). But the drug dose is not well tolerated in this model. CD3 deposition decreased in all the treated groups. Conclusions: PG490-88 along and combination with low dose FK506 prolonged renal allgraft survival in a stringent dog model. This agent attenuated acute humoral rejection by inhibiting complement activation and T-cell infiltration. C4c could be a good marker of complement activation in renal allograft. PG490-88 should be of great value in further clinical investigation of organ transplant.
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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 | 0.000 |
| 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 | 0.001 |
| 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".