| Project/Area Number |
60480475
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo College of Pharmacy |
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Principal Investigator |
OKA KITARO Tokyo College of Pharmacy, 薬学部, 助教授 (40057336)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO TOSHIHIKO Tokyo College of Pharmacy, 薬学部, 助手 (90173252)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1985: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | HPLC / Renal Transplantation / Serum Cortisol / Prednisolone / Immunosuppression / Prednisolone Sensitivity of Lymphocyte / Predictive Deagnosis of Acute Allograft Rejection / デキサメサゾン抑制試験 / 急性拒絶反応 / 内因性コルチゾール / 血中濃度 / 副腎皮質機能 / 薬物投与計画 |
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| Research Abstract |
To prevent an acute allograft rejection and severe lung infection is the most important therapeutic problems in immunosuppressive therapy of renal transplantation. However, it is difficult to know an appropriate immunosuppressive effect of prednisolone on graft survival in individual receipients. We considered whether there is phoarmacological relationaship between immunosuppressive and adrenal suppressive effects of prednisolone; the latter effect of prednisolone may easily measured by endogenous cortisol levels in plasma. In 1985, we developed an improved HPLC method for determination of suppressed amounts of plasma cortisol under the prednisolone therapy. Using this method we monitored the cortisol levels of our receipients. The results were compared with the actual clinical episodes of acute allograft rejection and lung infection. As the results, it has been clearly shown that the cortisol levels should be related to both clinical conditions. In 1986, our experiments have been continued to show that the adrenal suppression and immunosuppression of prednisolone are connected each other in terms of pharmacologically equivalent. To cosume the results experimentally, in 1987, we performed the in vitro study on lymphocyte sensitivity against prednisolone. The results showed that the cortisol levels after the operation correlates well to the lymphocyte sensitivity before the operation. These findings showed that the steroid sensitivity of the patients before (as the lymphocyte sensitivity against prednisolone in vitro) and after (as the plasma levels of cortisol) the operation may be reasonably applied to predict the allograft rejection and severe lung infection as well. Dexamethasone suppression test should be studied as a more easy clinical test to determine the steroid sensitivity of the individual patients as early as possible before the oncet of the drug therapy.
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