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Diabetes mellitus is associated with a higher oxidative stress and reduced activity of the antioxidant defense system in different brain regions. Results from numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents. It is well established that polyphenols exert potent antioxidant and protective functions. Based on recent findings, one potential target for the antioxidant/antinflammatory properties of polyphenols is the heme oxygenase (HO)-1 pathway. Among various compounds tested silibinin, the main component of silymarin, has been shown to possess a strong antioxidant effect in various experimental models; however a study on the possible neuroprotective effect of this compound on the brain of diabetic animals is currently lacking. Therefore, we studied and measured in lean mice (db/m) and knock out mice for the leptin receptors mice (db/db) the effect of silibinin on HO-1 protein levels, non proteic thiol groups, isoprostanes and 8-OH deoxyguanosine (markers of lipid peroxidation and DNA damage, respectively) in different brain regions. Our results showed that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition.

The genotype of apolipoprotein E was examined in 173 sporadic Alzheimer's disease (AD) patients, 132 with late onset (LOAD) and 41 with early onset (EOAD), and in 174 healthy matched controls from Sicily. Despite a low frequency of the epsilon 4 allele (6.3%, 95% CI: 4.2--9.4) in controls, epsilon 4 allele was a stronger predictor of AD risk (odds ratio: 5.8, 95% CI: 3.5--9.4; p0.0001) than in most of the studies performed in other regions of Italy, and it has no influence on age at onset. epsilon 4/epsilon 4 and epsilon 4/epsilon 3 genotypes were similar predictors of AD risk. Conversely, a decreased risk was found in epsilon 3 allele carriers (odds ratio: 0.3, 95% CI: 0.2--0.4; p0.0001), which remained significant when considering EOAD cases only (odds ratio: 0.2, 95% CI: 0.1--0.4, p0.0001). In conclusion, differences in association strength of epsilon 4 allele with AD between Sicily and other regions of Italy suggest an influence of complex gene-gene and gene-environment interactions.

The pathogenic mechanism of neural tube defects may involve genetic polymorphisms and nutritional factors related to homocysteine metabolism. We evaluated the association of polymorphisms of three genes affecting vitamin B12-dependent remethylation of homocysteine, transcobalamin (TC), methionine synthase (MTR) and MTR reductase (MTRR), combined or not with methylenetetrahydrofolate reductase (MTHFR), with the risk of having neural tube defect in 40 children with spina bifida and 58 matched controls from South Italy. MTR 2756 AG/GG, TC 777 CG/GG /MTHFR 677 CC and MTRR 66 GG /MTHFR 677 CC genotypes increased the risk with odds ratios of 2.6 (P=0.046), 2.4 (P=0.028) and 4.5 (P=0.023), respectively. In contrast, MTHFR 677 TT was protective (odds ratio=0.11, P=0.009). In conclusion, genetic determinants affecting the cellular availability or MTRR-dependent reduction of B12 may increase the risk of spina bifida.

We evaluated the allele (and genotype frequencies in 60 Down syndrome (DS), 25 mothers and 57 controls from Sicily and its relation with mental retardation. DS patients and sex ratio (M:F) was 22.1+/-10.5 and 1.14, respectively. Allele varepsilon4 and varepsilon3 frequencies were respectively lower (P=0.015) and higher (P=0.005) in DS patients compared to controls. Genotype varepsilon3/varepsilon4 and varepsilon3/varepsilon3 were less (P=0.03) and more frequent (P=0.001) in DS patients, with respective odd ratios of 0.31 (CI at 95%: 0.18-0.49) and of 4.4 (CI at 95%: 3.4-5.7). No difference of allele (distribution was found in function of the grades of mental retardation according to DMS-IV. Our results show that the implication of Apo-E4 in the pathogenesis of Alzheimer disease cannot be extrapolated in that of dementia of DS.