Central Neurodegenerative Diseases

There is increasing evidence that a number of common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis may include adverse responses to oxidative stress. Small intervention trials in patients with these diagnoses have reported some improvement with either vitamin E (Muller, 1994; Sano et al., 1997) or vitamin C (Morris et al., 1998; Riviere et al., 1998), but it is still too early to draw any conclusions as to the usefulness of these compounds in these diseases, or to their ability to delay onset of the disease.

Diabetes Mellitus

Cardiovascular complications are the major causes of death in diabetes. The incidence of coronary heart disease in type II diabetes is significantly higher than that in the general population (Kannel and McGee, 1979). In addition, individuals with diabetes experience microvascular complications (retinopathy, neuropathy, and nephropathy) secondary to their hyperglycemia. Thus, oxidative processes also may play an important role in the development or progression of diabetes mellitus.

In vitro oxidation of LDL from patients with diabetes mellitus proceeds at an accelerated rate, which suggests that they are more susceptible to the atherogenic process (Chisolm et al., 1992; Nishigaki et al., 1981; Reaven et al., 1995; Tsai et al., 1994). The several ways in which oxLDL is potentially more atherogenic than native LDL have been discussed above (see section “Cardiovascular Disease”).

Diabetics tend to have smaller, denser LDL (associated with hypertriglyceridemia) and these LDLs are more susceptible to oxidative modification ex vivo (Feingold et al., 1992). The TRAP of plasma from patients with insulin-dependent diabetes is decreased (Tsai et al. 1994), which may account in part for the greater susceptibility of their LDL to oxidation.

Microvascular complications are believed to be the ultimate consequences of nonenzymatic glycosylation and the progressive accumulation of advanced glycosylation end products (AGEs). There is evidence that the formation of these complex carbohydrate-protein and carbohydrate-lipid complexes is accompanied and accelerated by oxidative processes, which may lead to diabetic complications (Brownlee et al., 1988; Dyer et al., 1993; Hunt et al., 1988; McCance et al., 1993; Mullarkey et al., 1990). The glycosylation process is associated with increased formation of free radicals, and the possi-



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