To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.

As a growth factor, Rhizobium meliloti required cobalt ion, or vitamin B12 which was found to be incorporated into the cells without decomposition to cobalt ion. Trial of replacement for cobalt ion by the addition of various compounds to the cobalt-deficient medium revealed that methionine could substitute for cobalt ion and promote the growth in response to its concentration. Furthermore, B12-dependent methionine synthetase was demonstrated in the cell-free extracts of this microorganism. The morphological change of R. meliloti by the additions to the medium was observed microscopically. Cowles et al. showed that the requirement

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Ribonucleotide reductase from Rhizobium meliloti grown on the cobalt-deficient medium containing methionine was purified about 37-fold by streptomycin treatment, ammonium