On the basis of the mechanism of action of new antiandrogens, 16β-alkyltestosterones (1) and 16β-alkyl-19-nortestosterones (2), we designed and synthesized a series of 17-deoxyandrost-4-en-3-ones (12-14, 16, and 19) having substituent (s) at C-1, C-6, and C-7 positions and 17-deoxy-16β-alkylestr-4-en-3-ones (6) together with 17-deoxytestosterone (7) and 17-deoxy-19-nortestosterone (6 : R=H). The antiandrogenic activity was determined using immature orchiectomized rats treated with testosterone propionate. These compounds except 6 were found to show considerable antiandrogenic activity by subcutaneous or oral administration. The biological result means that 17β-hydroxyl group on the steroids was not indispensable for the manifestation of antiandrogenic activity. A new formylation reaction using orthoformate-boron trifluoride etherate instead of Vilsmeier reagent was described for the preparation of 6-formyltestosterone derivatives (9 and 22)

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Der Verfasser hat eine Untersuchung an gesunden, männlichen, ca. 300g. schweren Meerschweinchen unter folgenden Bedingungen augestellt:
a) Intratracheale Einführung einer Emulsion von lebenden, humanen Tuberkelbacillen (0.001mg.) nach. vorausgegangener intratrachealer Einführung von Lipiodol (0.5cc.).
b) Intratracheale Einführung eines mit Lipiodol (0.3cc.) und lebenden, humanen Tuberkelbacillen (0.001mg.) gemischten Oelpräparates.
c) Intratracheale - Einführung von Lipiodol (0.5cc.) nach vorheriger intratrachealer Einführung einer Emulsion von lebenden, humanen Tuberkelbacillen (0.001mg.).
Die Resultate waren folgende:
1) Wenn man eine bestimmte Menge von Lipiodol per Trachea in die Lunge einspritzt, nachdem 3 Wochen vorher eine intratracheale Einführung von lebenden, humanen Tuberkelbacillen ausgeführt worden war, so findet man, dass die Tuberkulose in der Lunge weiter fortgeschritten ist. Ein Stillstand oder eine Besserung tritt in diesen Fällen nicht ein.
2) Wenn man eine Emulsion von lebenden, humanen Tuberkelbacillen intratracheal in die Lunge einführt, nachdem vorher eine bestimmte Menge Lipiodol in die Lunge eingespritzt worden war, so findet, man, dass die Lungentuberkulose daruach nicht so stark fortgeschtritten ist.

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16β-Ethyl-17β-hydroxyestr-4-en-3-one (oxendolone) (1), a new antiandrogen, was synthesized starting from dehydroepiandrosterone (2). 3β-Acetoxy-16β-ethylandrost-5-en-17β-ol (3), prepared from 2 by stereospecific introduction of 16β-ethyl substituent, was converted into 3β, 17β-diacetoxy-5α-chloro-16β-ethyl-androstan-6β-ol (5) by acetylation and then chlorohydrination. Treatment of 5 with lead tetraacetate gave 3β, 17β-diacetoxy-5α-chloro-16β-ethyl-6β, 19-oxidoandrostane (6) in 96% yield. 6 was transformed into 17β-acetoxy-16β-ethyl-6β, 19-oxidoandrost-4-en-3-one (8) by two steps. Reductive cleavage of an oxido bond of 8 with zinc followed by oxidation with pyridinium chlorochromate yielded 17β-acetoxy-16β-ethylandrost-4-ene-3, 19-dione (10) in 75% yield. Treatment of 10 with sodium hydroxide followed by acid hydrolysis gave 1 in good yield.

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Reaction of γ-ketoamyl alcohol with diethyl oxalate in the presence of sodium ethoxide gave ethyl 5, 6-dihydro-4, 8-dioxo-4H, 8H-pyrano [3, 4-b] pyran-2-carboxylate (IV). Treatment of the other γ-keto alcohols (I, II, III) with diethyl oxalate in the presence of a base afforded dihydropyrones (IX, X, XI). Reaction of IV with primary amines yielded pyridone derivatives.

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痒みは，皮膚表層の生体防御感覚であり，マスト細胞，ケラチノサイト，T細胞，一次感覚ニューロンなどが産生・放出するアミン，ペプチド，サイトカイン，プロテアーゼ，脂質メディエーターなど多種多様な因子が起痒因子となる．痒みの受容にTRPV1チャネルを発現する一次感覚ニューロンが重要な役割を果たす．すなわち，TRPV1チャネルは起痒因子による一次感覚ニューロンの発火に関与する．一次感覚ニューロンのガストリン放出ペプチドは脊髄後角における痒み信号の伝達に関わり，BB₂ボンベシン受容体を発現する後角ニューロンは多様な痒み信号の入力を受ける．脊髄後角では下行性ノルアドレナリン作動神経がα-アドレナリン受容体を介して痒み信号の伝達を抑制する．脳および脊髄のμ-およびκ-オピオイド受容体も痒み信号の調節に関わる．

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The recent discovery of the new family of compounds, named leukotrienes because of their origin from leukocytes and a structural characteristic, the conjugated triene, has significantly increased our knowledge of arachidonic acid metabolism.
This review will focus on the chemistry leading to the complete stereochemical elucidation of the leukotrienes, as well as more recent synthetic advances.

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Oxidation of succinate and NADH in UQ-depleted mitochondrial preparations was restored by some low molecular weight quinones including QSA-10 (idebenone). QSA-10 inhibited lipid peroxidation dependent on NADH (NADPH)/ADP-Fe^lt:3+> in canine brain mitochondria and protected the resulting inactivation of NADH-Cyt c reductase activity. QSA-10 did not virtually affect the activities of succinate oxidase in canine and rat brain mitochondria and suppressed the oxygen consumption in NADH oxidation, which might be related to the inhibition of lipid peroxidation. These results, supported by those from ex vivo tests, suggest that QSA-10 acts as an electron carrier in respiratory chains and functions as an antioxidant against membrane damage caused by lipid peroxidation in brain mitochondria.

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