Peter J. Oates

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Diabetic hyperglycaemia causes a variety of pathological changes in small vessels, arteries and peripheral nerves. Vascular endothelial cells are an important target of hyperglycaemic damage, but the mechanisms underlying this damage are not fully understood. Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced(More)
Sorbitol dehydrogenase (hSDH) and aldose reductase form the polyol pathway that interconverts glucose and fructose. Redox changes from overproduction of the coenzyme NADH by SDH may play a role in diabetes-induced dysfunction in sensitive tissues, making SDH a therapeutic target for diabetic complications. We have purified and determined the crystal(More)
Similar vascular pathological conditions are observed in diabetic animals and those with diet-induced hypergalactosemia. Both diabetes and hypergalactosemia are believed to cause vascular dysfunction via a common biochemical mechanism. In this study, we have found that both diabetes and hypergalactosemia in the short term (2-4 months) can increase total(More)
OBJECTIVE Our objective was to determine whether impaired ovarian function induced by short-term creation of a galactosemic state in the rat might be prevented by the coadministration of an aldose reductase inhibitor. STUDY DESIGN Prepubertal Sprague-Dawley rats were fed four different diets including (1) control, (2) 40% galactose, (3) 40% galactose and(More)
This chapter critically examines the concept of the polyol pathway and how it relates to the pathogenesis of diabetic peripheral neuropathy. The two enzymes of the polyol pathway, aldose reductase and sorbitol dehydrogenase, are reviewed. The structure, biochemistry, physiological role, tissue distribution, and localization in peripheral nerve of each(More)
The exaggerated flux through polyol pathway during diabetes is thought to be a major cause of lesions in the peripheral nerves. Here, we used aldose reductase (AR)-deficient (AR(-/-)) and AR inhibitor (ARI)-treated mice to further understand the in vivo role of polyol pathway in the pathogenesis of diabetic neuropathy. Under normal conditions, there were no(More)
Concentrated ethanol causes gastric lesions by a mechanism that is poorly understood. We have investigated this mechanism in the rat stomach via gross morphologic, videomicroscopic, histochemical, and pharmacologic approaches. Within 1 min of contact, ethanol caused diffuse mucosal hyperemia. By 5 min, hyperemia greatly intensified at some mucosal sites.(More)
Diabetes increases the incidence of cardiovascular disease as well as the complications of myocardial infarction. Studies using animal models of diabetes have demonstrated that the metabolic alterations occurring at the myocyte level may contribute to the severity of ischemic injury in diabetic hearts. Of the several mechanisms being investigated to(More)
Increased flux of glucose through the polyol pathway may cause generation of excess reactive oxygen species (ROS), leading to tissue damage. Abnormalities in expression of enzymes that protect against oxidant damage may accentuate the oxidative injury. The expression of catalase (CAT), CuZn superoxide-dismutase (CuZnSOD), glutathione peroxidase (GPX), and(More)
Diabetic kidney disease, or diabetic nephropathy, is the leading cause of kidney failure in developed countries and is projected to place an increasingly heavy burden on medical, social and economic systems worldwide. Existing therapies can slow, but do not stop, disease progression. Recent data from preclinical models and patients with diabetes emphasize(More)