Resveratrol inhibits isoprostane production in young and aged rat brain.

Resveratrol (3,5,4-trihydroxystilbene), a viniferin polyphenolic compound, has been shown to have neuroprotective effects and we tested its possible antioxidant activity in young and aged rat brain, evaluating, in vitro, synaptosomal 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) production as a marker of oxidative stress. We found that in young rat brain synaptosomes resveratrol perfusion had no effect on basal 8-iso-PGF2alpha production, but quenched to basal levels the increased 8-iso-PGF2alpha production induced by hydrogen peroxide. On the other hand, in aged rats, resveratrol was able to decrease 8-iso-PGF2alpha production both basally and after hydrogen peroxide-induced oxidative stimulus. In conclusion, our findings show that the antioxidant effects of resveratrol in rat brain could play a neuroprotective role in aging, when the increased burden of oxidative stress is faced by defective antioxidant mechanisms.

Detection of metazoan species as a public health issue: simple methods for the validation of food safety and quality.

Species identification represents a critical issue in food chain safety and quality control. Several procedures are available to detect animal proteins in cattle feed or to trace transgenic foods. The most effective approach is based on the use of DNA as a marker. Amplification of DNA provides rapid, sensitive and specific protocols. Several target genes can be used, but new insights come from the mitochondrial genome, which is naturally amplified in each cell and shows a remarkable resistance to degradation. These are key points when analysing complex matrices such as foods, animal feedstuff or environmental samples. Traceability is important to prevent BSE or to monitor novel foods, such as genetically modified organisms. Amplification is commonly performed, but it requires expertise and a molecular biology laboratory to perform restriction analysis, electrophoresis or gel staining for the visualisation of results. Hereby, we consider a strategy based on multiple nested amplification and reverse hybridisation assay that virtually requires only a thermocycler and a water bath. The protocol is rapid and simple and can simultaneously detect different species in a DNA sample. This promising approach allows microarray developments, opening up to further perspectives. An international application has been published under the patent cooperation treaty. Presently, a ban on feeding ruminants on cattle-derived proteins is in force in Europe and USA. The identification of metazoan traces in a sample is not only a mere preventive measure for BSE, but represents a possible screening system for monitoring biotechnology products and procedures, as well as a quality control strategy to assure consumer's rights.

The polymorphisms -318C>T in the promoter and 49A>G in exon 1 of CTLA4 and the risk of aplastic anemia in a Caucasian population.

Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.

Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.