Masayasu Kurono

Effects of a new aldose reductase inhibitor, (2S, 4S)-6-fluoro-2′,5′-dioxospiro[chroman-4,4′-imidazolidine]-2-carboxamide (SNK-860), on the slowing of motor nerve conduction velocity and metabolic abnormalities in the peripheral nerve in acute streptozotocin-induced diabetic rats

The effects of a new aldose reductase inhibitor (ARI), (2S,4S)-6-fluoro-2,5-dioxospiro[chroman-4,4-imidazolidine]-2-ca rboxamide (SNK-860), on the slowing of motor nerve conduction velocity (MNCV) and metabolic abnormalities in sciatic nerve were investigated in acute streptozotocin (STZ)-induced diabetic rats. MNCV in the diabetic rats was significantly slower 2 weeks after STZ injection. In the following 2 weeks, treatment with SNK-860 improved MNCV in a dose-dependent manner. The efficacy of 1 mg/kg SNK-860 was equipotent to that of 20 mg/kg sorbinil. Four weeks after STZ injection, increases in sorbitol levels, decreases in myo-inositol levels, and reductions in Na+, K(+)-adenosine triphosphatase (ATPase) activity were observed in sciatic nerves of diabetic rats. Administration of SNK-860 for 14 days beginning 2 weeks after the induction of diabetes inhibited these metabolic abnormalities in a dose-dependent manner. SNK-860 restored all of these parameters to normal levels at a dose of 2 mg/kg. In addition, close correlations were observed between MNCV and sorbitol levels (r = -.95) and between MNCV and myo-inositol levels (r = .93) in the sciatic nerve; a close correlation was also observed between sorbitol and myo-inositol levels in the sciatic nerve (r = -.86). Therefore, it is suggested that the effect of SNK-860 on the slowing of MNCV results from normalizing the above-mentioned metabolic abnormalities in the sciatic nerve of diabetics. Thus, SNK-860 may be useful in the treatment of diabetic neuropathy.

Determination of monosaccharides and sugar alcoholsin tissues from diabetic rats by high-performance liquid chromatography with pulsed amperometric detection

A sensitive and simple high-performance liquid chromatographic method has been developed to determine the concentration of monosaccharides and sugar alcohols in animal tissues. Five neutral monosaccharides (D-glucose, D-galactose, D-mannose, D-fructose, and D-ribose) and three neutral sugar alcohols (myo-inositol, glycerol, and D-sorbitol) predominate in the renal cortices and sciatic nerves of rats. These monosaccharides and sugar alcohols were extracted with distilled water, purified by deproteinization with ethanol, a Sep-Pak C18 cartridge, and columns of Dowex 50W-X8 and Amberlite CG-400, then separated on Ca2+ and Pb2+ cation-exchange columns, eluted with deionized distilled water at 80 degrees C, and detected using integrated pulsed amperometry. About 10 pmol of each sugar was detectable with a signal-to-noise ratio of 10:1. D-Glucose, D-fructose, D-sorbitol, and D-mannose were higher in both the renal and sciatic tissues of diabetic rats than in those of normal animals. D-Ribose and glycerol were higher in the renal cortex of diabetic animals.

Age-Related Cataract in the Hereditary Cataract Rat (ICR/1): Development and Classification

Lens opacification of the Ihara hereditary cataract rat (ICR/1 rat) was followed up with slit lamp biomicroscopy and photography up to 1 year after birth. The development of lens opacities was first recognized in the anterior superficial cortex of the equatorial region between 30 and 44 days of age. It progressed to maturity around 93-107 days after birth. Cataract development was classified into six stages. The increase of lens weight indicated a continuous lens growth after birth which seemingly even continued after the occurrence of lens opacities. After around 60 days of age, the lens showed a continuous increase of water content, suggesting a participation of increased water content in lens opacification.