耳鼻咽喉科領域において, 抗生剤の局所療法は, 病変部位に高濃度の薬剤移行を望み得ることから, 種々の中耳疾患に用いられる有用な治療法の一つである。しかしながら, 従来局所用製剤として用いられたFradiomycin (FRM), Chloramphenicol (CP) などは, いずれも聴器毒性などの問題があり, その使用は大きく制限されている。一方, 上記薬剤の出現以降, 現在まで新しい局所用製剤の開発は, ほとんどみられず, 臨床的には耳漏からの検出菌の感受性に合致した薬剤を調製して用いざるを得ないのが現状である。
今回, 我々は, Fosfomycin (FOM) の中耳局所用製剤の基礎的研究として, 鼓室内投与による蝸牛, 前庭器への影響を形態学的には走査型電子顕微鏡 (SEM) を用いて, 又, 生理学的には聴性脳幹反応 (ABR) を用いて観察したので, 若干の文献的考察を加え報告する。

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Fosfomycin (FOM) 2, 3%及び5%液0.1mlを1群4匹の雄性Hartley系モルモットの人工的に作成した鼓膜穿孔から5日間にわたり点耳し聴覚器への影響について検討した. なお, 対照薬群としてKanamycin A (KM) 2%液点耳群も設定した.
点耳終了後10日目に屠殺して走査電子顕微鏡下で蝸牛外有毛細胞聴毛及び内有毛細胞聴毛の形態変化を検索した.
その結果, 特に薬物起因と考えられる変化を認めなかつた.
FOM3%及び5%液及びKM2%液のそれぞれ0.1mlを1群3匹の雄性Hartley系モルモットの人工的に作成した鼓膜穿孔から点耳し, 蝸牛リンパ液中の薬物濃度を測定した.
その結果, FOM3%はKM2%に比べて低い最高濃度を示したが, AUCでは高い値を示した. 又, T1/2の値はFOMでは約4.8時間であつたが, KMでは約2.3時間であつた. FOMのAUC及び最高濃度の値はほぼFOM濃度に依存して増加した.
以上の結果から, FOMは中耳腔から正円窓膜を容易に通過し, 蝸牛リンパ液中に移行し, KMに比べて長く分布するが, 聴覚器蝸牛の内, 外有毛細胞に毒性的影響を与えないと示唆される.

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Fosfomycinは, Streptomyces wedmorensisおよびS. fradiaeなどの放線菌によつて産生される新規抗生物質である1～3)。
本物質は, Fig. 1に示すようなエポキシ環をもつきわめてユニークな化学構造をもち, 細菌細胞壁合成の初期過程を阻害し, グラム陰性菌および陽性菌等に有効な広域スペクトルをもつ抗生物質で, 他剤との交叉耐性はなく, 特にグラム陰性菌感染症に卓越した効果をもつ物質である8～14)。
本物質のカルシウム塩は経口用製剤として, またナトリウム塩は注射用製剤として開発されている。
今回, Na塩 (Fosfomycin-Na塩, 以下FOM-Na) の肝機能におよぼす影響について検討したので, 得られた知見を報告する。

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In order to improve wear resistance of white cast iron, cermet powder layer only and cermet powder layer mixed with some metallic powder were inserted by molten 27 mass% Cr white cast iron at 1773K. Various sizes of the cermet powder were adopted for the insertation. The microstructure of surface and vertical cross-section of the inserted layer was examined to investigate castability of the molten cast iron for these powder layer. The results obtained are as follows. (1) For the cermet powder size of more than 3.4mm, the inserted layer shows satisfactory metallographic structure. (2) For the cermet powder size of less than 3.4mm, many voids are located in the inserted layer and cermet powder remain, but good metallographic structure is obtaind by the addition of Ni powder or Cr powder. (3) For the mixed cermet powder added 50 vol.% Ni powder, a compression method to make a compact is available to obtain a good microstructure of inserted layer. (4) A suspension method for the cermet powder in the mold is also effective to obtain the good microstructure because it is easy to obtain a good admission of the molten cast iron into the cermet powder.

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  In cast-in insertions of mild steel in cast iron, molten cast iron sometimes melts a part of the inserted steel, causing serious damage to the casting products. To clarify the mechanism of this phenomenon, the influence of the fluid flow of molten cast iron on the dissolved loss of inserted steel was quantitatively evaluated. The molten cast iron was poured into a self-curing mold with an inserted mild steel ring near the open bottom end. The height of the sprue was changed from 500mm to 50mm. The higher the head height, the larger was the fluid velocity. The change in the thickness of inserted steel ring was measured in relation with the pouring time. The experimental results showed that the thickness of steel linearly decreased with the increase in pouring time and flow velocity of the molten cast iron. Widmanstätten ferrite structures and a slightly large amount of pearlite appeared near the surface of the dissolved steel. Temperature measurement and analysis revealed that the dissolved loss of steel started at a temperature considerably lower than the melting point of cast iron. This indicates that the mild steel surface was softened by the heat of molten cast iron and eroded by the fluid flow.

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  High chromium cast irons show superior abrasion resistance due to their chromium carbides. Their abrasion resistance is improved by insert casting with cemented carbide. The effects of high temperature exposure during insert casting on the microstructures of cemented carbide were investigated in this research. A high chromium cast iron (2.7%C-27%Cr) and cemented carbide (WC-13.7%Co) round bars were prepared. The cemented carbide round bars were dipped in molten high chromium cast iron at 1596 K. The dipped round bars were pulled up after the elapse of 30 to 180 s. Microstructures of dipped cemented carbide round bars were changed from homogeneous sinter structure to three-layer structure, cemented carbide, diffusion layer and reaction layer. The thicknesses of the diffusion layer and the reaction layer were increased with increase of dipping time. FE-EPMA analysis revealed that the diffusion layer was formed by the elution of Co from the cemented carbide and diffusion of Fe and Cr from the molten high chromium cast iron into the cemented carbide round bar. In addition, rectangle particles were randomly distributed in the diffusion layer. The equivalent circular diameter of the rectangle particle was increased with increasing dipping time. The vickers hardness of the diffusion layer decreased about 30% relative to the cemented carbide but higher than that of high chromium cast irons. The inserted cemented carbide is thought to have contributed to improving abrasion resistance. I was suggested that thin diffusion layers are more effective for improving abrasion resistance.

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