Peripheral nerve repair following ARI treatment.
In this placebo-controlled double-blind clinical trial, ARI-treatment was accompanied by small but statistically significant improvements in clinical and electrophysiological indices. These improvements were associated with a lowering of nerve sorbitol levels and significant improvements in quantitative structural parameters. These data suggest that an activated polyol-pathway plays a continuous pathogenetic role even in advanced clinically overt diabetic neuropathy, and that the metabolic abnormalities mediated by the polyol pathway are intimately associated with structural and functional changes and ultimately clinical symptoms. The regenerative and reparative responses to a potent ARI like sorbinil suggest that advanced neuroanatomical changes believed to underlie overt clinic polyneuropathy are at least partly reversible, and that extrapolated over longer treatment periods ARI's may substantially ameliorate the structural changes and the clinical symptoms associated with diabetic neuropathy. As indicated by animal studies ARI's may become valuable adjuncts to the therapeutical arsenal not only in the treatment of diabetic neuropathy and other chronic diabetic complications, but also as a prophylactic regimen, provided that safe compounds can be developed.
Sima
A A
AA
Neuropathology Research Laboratories, University of Manitoba, Winnipeg, Canada.
Nathaniel
V
V
Greene
D A
DA
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001369:Axons / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000473:pathology; D004311:Double-Blind Method; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology; D011901:Ranvier's Nodes / Q000378:metabolism / Q000473:pathology; D013012:Sorbitol / Q000378:metabolism
D007093:Imidazoles; D048289:Imidazolidines; D013012:Sorbitol; D000449:Aldehyde Reductase; C026411:sorbinil