| Co-Investigator(Kenkyū-buntansha) |
MIZUGAKI Mitinao Tohoku University School of Medicine, Department of Pharmacy, Professor, 医学部・附属病院, 教授 (60004595)
YAMAMOTO Syuzo Tokushima University, School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (50025607)
MUROTA Seiitsu Tokyo Medical and Dental University, School of Dentistry, Professor, 歯学部, 教授 (50072989)
OUTI Kazuo Tohoku University, Department of Pharmacy, Professor, 薬学部, 教授 (20006357)
KATORI Makoto Kitasato University School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (50050365)
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| Research Abstract |
The method to measure 11-dehydro-thromboxane A_2(TXA_2) in the biological fluid was established by the previous research project. In this following project we performed the clinical application of this method in various human diseases as well as animal models of diseases. Over productions of TXA_2 were suspected in patients with myocardial infarction, cerebral infarction, diabetes mellitus, toxemia of pregnancy and bronchial asthma who showed higher urinary excretions of 11-dehydro-TXB_2, Physiological and pathophysiological roles of TXA_2 were elucidated. Furthermore, various immunoaffinity column and HPLC separation method were developed for the clean up of eicosanoids from the biological fluids and the HPLC-laser system to detect the small amount of eicosanoids was also developed.
On the other hand, EIA kit for 2, 3-dinor-6-keto-prostaglandin (PG)F_1alpha, the stable metabolite of prostacyclin (PGI_2) was developed and we shared in the work for the standardization and clinical applic
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ation of this method. The separation of 2, 3-dinor-6-keto-PGF_1alpha from biological fluid was needed by either immunoaffinity column using anti-6-keto-PGF_1alpha antibody or anti-2, 3-dinor-6-keto-PGF_1alpha antibody or by HPLC before the measurement by EIA.Urinary excretion of 2, 3-dinor-6-keto-PGF_1alpha in man was about 100-400 pg/mg creatinine measured either by EIA or by GC/SIM method. There were no sex related differences and urinary levels were affected mainly by the systemic production rate rather than the renal production rate. Thus the 2, 3-dinor-6-keto-PGF_1alpha seems suitable as the index of systemic production rate of PGI_2. This method was useful to measure the levels in the tissue culture media and in the biological fluid from inflammatory tissue. We also applied clinically to measure the urinary excretion of levels in patients with hypertension, diabetes mellitus and toxemia of pregnancy. The establishment of the measurement of major stable metabolites of TXA_2 and PGI_2, in turn, made it possible to clarify the production balance between TXA_2 and PGI_2 in various diseases. Surplus TXA_2 production than PGI_2 was found in patients with essential hypertension as well as diabetes mellitus.
Thus, most important problems to measure TXA_2 and PGI_2 in the biological fluid was dissolved by these projects and these methods seems to be useful tools to clarify the pathphysiological roles of TXA_2 and PGI_2 in man. Less
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