サリチラート,酸化窒素,マラリア,レイ症候群
I Clark1, R Whitten, M Molyneux
1Division of Biochemistry & Molecular Biology, School of Life Sciences, Australian National University, Canberra, Australian Capital Territory. ian.clark@anu.edu.au
Lancet (London, England)
|September 18, 2001
まとめ
発熱の子供にサリチラートを使用すると,酸化窒素合成酵素 (iNOS) を強化することによって,マラリアやレイ症候群などの感染症を悪化させる可能性があります. サリシラート使用を抑止することは,レイ症候群の発生率の減少と相関しています.
科学分野:
- 医学科学 医学科学 医学科学 医学科学
- 病理学 パトロジー
- 薬理学 薬理学とは
背景:
- レイ症候群の発生率は,発熱児のサリチラート使用を抑止した後,世界的に減少しました.
- サリシラート毒性は,サリシラートが広く使用されているアフリカの地域で一般的な重度のファルシパラムマラリアと臨床的特徴を共有しています.
- レイ症候群に対する提案された過敏性メカニズムには,確立された生物学的経路が欠けていた.
研究 の 目的:
- サリシラート使用,感染症,レイ症候群を結びつける潜在的なメカニズムを調査する.
- 誘導性酸化窒素合成酵素 (iNOS) がサリシラート媒介による感染症の悪化における役割を調査する.
主な方法:
- サリシラート毒性およびマラリアに関する臨床観察のレビュー.
- インターフェロンガンマ-iNOS経路に対するサリシラートの作用に関する実験的証拠.
- 致死性マラリア,急性発熱,レイ症候群の症例におけるiNOS発現の分析.
主要な成果:
- サリシラートは,インターフェロンのガンマ信号伝達経路を強化し,iNOSの活動を延長します.
- 強いiNOS発現は,致命的なマラリアとアフリカの子供たちの急性発熱で観察されました.
- 致命的なレイ症候群の組織に広く発現したiNOSが発見されました.
結論:
- 発熱児のサリチラート使用は,iNOS強化により,ファルシパラムマラリアなどの深刻な感染症を悪化させる可能性があります.
- レイ症候群の発生率の減少は,サリチラート使用量の減少と関連している可能性があります.
- サリシラートによるiNOS経路の調節は,レイ症候群の病原性の潜在的なメカニズムです.
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