Identification of new fatty acids associated with pathogenesis of ischemia and various types of intoxication and its application to a new diagnostic method

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1) Research on lipid per-oxidation and injury associated with carbon monoxide (CO) poisoningThere were both necrotic and apoptotic death in the basal ganglia, cortex, and hippocampus in a subacute CO poisoning case. The distribution of the lesions could not be explained by ischemia. In a rat model of rat CO poisoning (90 min CO exposure followed by 2 days recovery), there was necrosis, particularly in the sub-cortex. There was intense staining of a lipid peroxide product, 4-hydoroxynonenal (HNE), in the nuclei of the necrotic area. Hypothermia attenuated the necrosis and HNE-generation. Additionally, by the new assay system, another lipid per-oxidation product 7-hydroxysterol was shown to be increased after CO-exposure Hypothermia attenuated the 7-hydroxysterol generation induced by CO, indicating the involvement of lipid per-oxidation in the pathogenesis of CO poisoning and the possibility of clinical application of hypothermia.2) Research on lipid peroxidation and injury associated with myocardial infarctionIn a rat model of myocardial infarction, HNE and TNF-α was greatly increased, while the increase was attenuated by ischemic preconditioning (IP : cycles of brief time of ischemia-reperfusion) that mimic the pre-infarction angina. IP attenuated the enhanced TNF-α generation in the infracted myocardium and the activation of reactive oxygen-associated transcription factor NF κ B, which is known to promote nitric oxide-mediated cell injury and leukocyte-associated inflammation.3) Research on the beneficial effect of CO exposure on ischemic cell death of cardio-myogenic H9c2 cells.CO exposure attenuated the necrotic death, reactive oxygen generation and HNE formation in the H9c2 cells induced by chemical ischemia through MAP kinase/ERK pathway.