誘導体lisurideの異型化赤血球誘発ラット脳梗塞に対する影響を検討した．生理食塩液で2倍希釈したラット自家血を高浸透圧性溶液(65% meglumine diatrizoate)と等量混合し，高浸透圧処理で形態変化および変形能低下を引き起こした異型化赤血球を含む混合液50μを，ラット左外頸動脈から逆行性に内頸動脈に注入して脳梗塞を誘発した．lisurideおよび対照として生理食塩液を，梗塞誘発30分前に皮下投与した．生理食塩液群では，脳梗塞誘発2時間以内にすべてのラットが死亡したが，lisuride0.002mg/kg群では生存時間の延長傾向が，0.01mg/kg群では有意な延長がみられた．脳梗塞誘発1時間後に，脳水分含量率，脳組織中Na⁺およびCa²⁺含量がそれぞれ増加したが，lisuride0.01mg/kg群では生理食塩液群に比していずれも有意な減少がみられた．梗塞誘発1時間後の別の脳から作成したヘマトキシリンエオシン染色標本について，組織障害に対する影響を検討したところ，lisuride0.01mg/kg群では組織障害の顕著な領域が生理食塩液群に比して約50%と有意に小さかった．またlisuride群では，大脳皮質および髄質神経細胞と髄質神経線維の変性が生理食塩液群に比してそれぞれ有意に軽減された．以上の結果から，lisurideは脳循環障害後の急性変化に対して有効であることが示唆された．

抄録全体を表示

種々の検討の結果, 迅速簡便な

12種の一斉分析法の構築に至った. 試料の前処理のミニカラムはCaptiva EMR-Lipidsが最適であった. 良好なMFが得られ, 2mLという少量で全化合物が完全に溶出し, かつ充てん剤に触れたときのepimerizationは起こらなかった. このミニカラムを用いた分析法の性能評価を実施したところ, 全ての化合物において, 選択性, 真度, 精度及び検量線の決定係数が目標値を満たす良好な結果が得られた. また, 低濃度でのLOQ及びLODが設定できたことにより, 10ng/g以下という微量のを検出するに十分な高感度分析が達成できた. 本分析法を用いて市販小麦の汚染調査を行った結果, いずれの化合物も検出されず, による汚染の可能性は低いことが示唆された.

抄録全体を表示

Effect of ergot alkaloids on (³H) -nucleosides uptake by dispersed cells from fresh female bovine anterior pituitary glands was examined, because we had interested in the mechanism of pituitary tumor regression following bromocriptine treatment and considered nucleic acid synthesis as an important process in the metabolism of these cells.
The anterior pituitary cells were implanted on culture tubes using D-valine minimal essential medium with serum to suppress the overgrowth of fibroblasts and then maintained in L-valine Dulbecco's modified Eagle medium.
(³H) -Uridine uptake by these cells was suppressed by bromocriptine, @-ergocriptine or ergotamine at a concentration varing from 10^-6M to 10^-5M, but not 10^-5M of lergotrile. Among these alkaloids, bromocriptine had most strong inhibitory effect and suppressed the uptake to below 25% of control value at the concentration of 10^-5M. Bromocriptine also inhibited the uptake of (³ H) -thymidine, (³ H) -cytidine, (³ H) -adenosine or (³ H) -guanosine in the same manner as (³H) -uridine. But neither (³H) -uracil, the base of uridine, nor (³H) -galactose uptake by cells was affected by bromocriptine. The incorporation of (³ H) -uridine or (³ H) -thymidine into TCA-insoluble fraction of the cells was also inhibited by bromocriptine as that in the total cells.
It was suspected that bromocriptine acted on distinct transport site of both ribonucleoside and deoxyribonucleoside, because a high concentration (3.3 X 10^-5M) of radio-inactive thymidine did not modify (³H) -uridine uptake by these cells as well as inhibitory effect of bromocriptine on it.
These effect of bromocriptine were not blocked by haloperidol, known as dopamine antagonist, at the same concentration as bromocriptine, and dopamine had no effect on (³ H) -uridine uptake by the cells. In addition, by adding 5 X 10^-4M of dibutyryl cyclic AMP into the medium, the effect of bromocriptine was also not affected. These data suggest that the effect of bromocriptine on nucleoside transport in anterior pituitary cells may be dependent on the other binding site than D-2 dopamine receptor in the anterior pituitary cell membrane.

抄録全体を表示

Although it is well known that bromocriptine (BC) is effective in the treatment of functioning pituitary adenoma, this agent sometimes causes severe gastrointestinal side effects. In this study, dihydroergotoxine mesylate (EX), which is composed of ergot alkaloids and is similar to BC, was administered to 11 patients with functioning pituitary adenomas who could not tolerate the adverse effects of BC. Three patients (27%) showed clinical improvement with EX treatment alone (1 to 6 mg/day). In another patient, computed tomography demonstrated tumor shrinkage. The remaining seven patients became able to take BC with no adverse effects, after 2 to 16 weeks starting EX therapy. No patients experienced adverse effects while taking EX. These results indicate that EX is a useful alternative to BC in the treatment of functioning pituitary adenoma, particularly in patients who cannot tolerate the side effects of BC. Moreover, pretreatment with EX appears to reduce the incidence of side effects of BC.

抄録全体を表示

Five ergot alkaloids were obtained in crystalline forms from the culture broth of Hypomyces aurantius. They were shown to be identical in physioco-chemical properties with clavine-type ergot alkaloids agroclavine, elymoclavine and chanocla-vine and with peptide-type ergot alkaloids ergokryptine and ergokryptinine.
The isolation of peptide-type ergot alkaloids has never been reported from the culture broth of a fungus other than Claviceps species. Our study demonstrates that Claviceps and Hypomyces have a close chemotaxonomical relationship.

抄録全体を表示