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Biomedical subjects

K Handa

Publications and source records attributed to K Handa.

At least 163 records · Page 9Linked to original sources

Electron spin resonance study on the mode of generation of free radicals of daunomycin, adriamycin, and carboquone in NAD(P)H-microsome system.

The mode of generation of free radicals of daunomycin, adriamycin, and carboquone in the NADPH-rat liver microsome system was studied at room temperature by electron spin resonance (ESR) spectroscopy. ESR signals of all these quinoid anticancer chemicals were detected when dissolved oxygen in the reaction mixture was consumed since the radicals are easilyaut oxidizable. All the radicals had an appreciable lifetime under anaerobic conditions. However, there were differences in the mode of their generation between daunomycin and adriamycin, on the one hand, and carboquone, on the other, with respect to the lag time and the effect of the amount of chemicals, pH of the medium, kind of electron donors, NADPH and NADH, and the presence of excess of DNA. Especially, ESR signal reappeared after the first signal had decreased considerably, in the case of daunomycin and adriamycin but not in carboquone. Intact Ehrlich ascites tumor cells also gave rise to an ESR signal of adriamycin and carboquone, but the former signal was prevented from appearing in the presence of glucose.

Animals↗

Stimulation of microsomal NADPH oxidation by quinone group-containing anticancer chemicals.

Several anticancer chemicals containing a quinone group were found to stimulate the aerobic oxidation of NADPH by liver microsomes. The enzyme responsible for the above reaction was identified as NADPH-cytochrome c reductase (EC 1.6.2.4), one of the microsomal flavoproteins. The fact that a catalytic amount (20 micronM) of these anticancer chemicals was sufficient to oxidize all the NADPH (100 micronM) indicates that they function as electron carries from the flavoprotein to molecular oxygen. As a corollary, Mitomycin-C and Carbazilquinone stimulated oxygen uptake by Ehrlich ascites tumor cells in the presence of glucose that Daunomycin and Adriamycin failed to do so, although the reason for it remains to be elucidated. Carbazilquinone, in contrast to others, also stimulated the microsomal NADH oxidation.

Animals↗

Generation of free radicals of quinone group-containing anti-cancer chemicals in NADPH-microsome system as evidenced by initiation of sulfite oxidation.

The prerequisit of reduction for activation of Mitomycin-C and unstability of its reduced form suggested investigation of the possible formation of free radicals (semiquinone forms) of a series of quinone-containing anticancer chemicals in vitro. The ability of rat-liver microsomes to initiate sulfite oxidation in the presence of NADPH was markedly enhanced by the addition of these chemicals. This strongly suggests that these chemicals participated in the process in the form of reactive free radicals. The reaction was specific for NADPH. Carbazilquinone was unique among others in that NADH can replace NADPH and its higher ability to initiate sulfite oxidation. Microsomes from Ehrlich ascites and AH-109A hepatoma cells were also effective, though to a lesser extent than those from rat liver on a protein basis. Generation of free radicals, though their biological significance is not clear at present, may be deemed an inherent chemical property of these chemicals.

Animals↗

A collaborative study of stroke incidence in Japan: 1975-1979.

A Japan Collaborative Study of Stroke covering 20 regional and occupational population groups was conducted with the support of the Ministry of Health and Welfare. In this study 17,423 males and 16,856 females, aged 40 to 69, were followed up prospectively from 1975 to 1979. The average annual incidence of all types of stroke was 3.94 for men and 2.52 for women per 1,000 population. The incidence of cerebral hemorrhage for men and women stood at 1.26 and 0.59 and that of cerebral infarction at 1.87 and 1.10 respectively. The difference in incidence between the sexes was large particularly in the age range of 40-49. The incidence of all types of stroke, cerebral hemorrhage and cerebral infarction increased with age. The incidence of all strokes in Japan during the period 1975-1979 appears to have decreased in comparison with that in 1960-1969, but tended to be still higher than that in Western countries.

Adult↗

Effects of gamma-oryzanol on serum lipids and apolipoproteins in dyslipidemic schizophrenics receiving major tranquilizers.

The subjects were 20 chronic schizophrenic patients with dyslipidemia (total cholesterol levels greater than or equal to 220 mg/dl, triglycerides greater than or equal to 150 mg/dl, or high-density lipoprotein cholesterol less than or equal to 40 mg/dl) who had been receiving neuroleptics for a mean of ten years. Each patient was given 100 mg of gamma-oryzanol three times daily for 16 weeks. Total cholesterol and low-density lipoprotein cholesterol levels, respectively, decreased significantly, from 204 and 124 mg/dl at baseline to 176 and 101 mg/dl at week 12. High-density lipoprotein cholesterol levels were 36.1 mg/dl at baseline and 35.9 mg/dl at week 12. Apolipoprotein (apo) B levels decreased significantly from 116 mg/dl to 101 mg/dl at week 16; apo A-II levels increased significantly from 31.7 mg/dl to 34.7 mg/dl; and the apo B/apo A-I ratio declined significantly from 0.99 to 0.84. No treatment side effects were recorded. It is concluded that gamma-oryzanol is safe and effective in the treatment of dyslipidemia.

Antipsychotic Agents↗