2006 Fiscal Year Final Research Report Summary
Clinical research and development of therapy for diphenylarsinic acid poisoning from a possible chemical warfare agent
| Project/Area Number |
16590811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ISHII Kazuhiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院人間総合科学研究科, 講師 (70323293)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Organoarsinic compounds / Diphenylarsinic acid / Cerebral blood flow scintigraphy / Cerebellar signs / Myoclonus / Tremors |
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| Research Abstract |
Diphenylarsinic acid (DPAA) is the chemical material of diphenylcyanoarsine and diphenylchloroarsine used to synthesize chemical weapons and it does not exist in nature. In March 2003, we noted a new clinical syndrome with prominent cerebellar symptoms in the residents of an apartment building in Kamisu, Japan. The well that provided drinking water for all of these apartments contained DPAA. Characteristics of the DPAA poisoning included temporo-occipital lobe symptoms such as sleep disturbance, memory impairment and visual disorder, and cerebellar-brainstem symptoms such as ataxia, myoclonus and tremors. Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants. DPAA was detected in urine, blood, nails and hair. Furthermore, phenylmethylarsinic acid (PMAA) and monophenylarsinic acid (PAA), which are biological metabolites from DPAA, were found by LC/MS/MS. DPAA could no longer be detected in the blood and urine at about 200 days and 300 days after termination of exposure, respectively. Animal experiment revealed that DPAA was easy to accumulate in the central nervous system(CNS), especially in the cerebellum-brainstem significantly. Elimination of DPAA from the central nervous system was very slow. DPAA tends to accumulate in the CNS more than in other organs. Cerebral functional imaging views such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) showed hypoperfusion and hypometabolism of glucose in related symptomatic regions. These facts explain the clinical CNS symptoms of DPAA poisoning, that is, the cerebellum and brainstem are the target regions of DPAA in CNS. It is thought that prolonged abnormality of functional imaging views in relevant regions reflect the long-term influence of DPAA against CNS. We believe that SPECT and PET can be used as a DPAA exposure index and biomarker for treatment or recovery.
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Research Products
(22 results)
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[Journal Article] 小児におけるジフェニルアルシン酸等化合物中毒2005
Author(s)
岩崎信明, 石井一弘, 宮本信也, 武田徹, 田中竜太, 大戸達之, 斎藤貴志, 松井陽, 新健治, 絹笠英世, 土田昌宏, 家島厚, 緒方剛, 佐藤秀郎
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Journal Title
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Satoh H. diphenylarsinic acids intoxication in infant.2005
Author(s)
Iwasaki N, Ishii K, Miyamoto S, Takeda T, Tanaka R, OOto T, Saitoh T, Matsui A, Shin K, Kinugasa H, Tsuchida M, Ieshima A, Ogata T
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Journal Title
Brain ＆ Development 37
Pages: Suppl, 180
Description
「研究成果報告書概要(欧文)」より
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