Background:The inhibitory mechanism of A␤42 aggregation by flavonoid is fully unknown. Results: The oxidant enhanced the inhibitory activity of (ϩ)-taxifolin against A␤42 aggregation by forming A␤42-taxifolin adducts between the Lys residues and oxidized (ϩ)-taxifolin. Conclusion:The inhibitory activity of catechol-type flavonoids requires autoxidation to form an o-quinone to react with Lys. Significance: These may help design promising inhibitors against A␤42 aggregation for Alzheimer disease therapy.

To study the molecular epidemiology of respiratory syncytial virus (RSV) in a community, children with acute respiratory symptoms at a pediatric outpatient clinic in Niigata, Japan, were analyzed over three seasons from Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory disease in infants and young children and is found mainly in the late fall, winter, and spring (2, 8, 13, 15). Bronchiolitis and pneumonia are observed most frequently during the first few months of life (2,8,17). Almost all children are infected with RSV by age 2 years, and half have experienced two infections (8,11,17).RSV strains have been classified into antigenic groups A and B (RSV-A and RSV-B, respectively) on the basis of the reactivities of the viruses with monoclonal antibodies directed against the attachment glycoprotein (G protein) (1,7,12,19) and also by genetic analyses (9,25,26). G protein is the most variable RSV protein (10,14,19), and its C-terminal region (the second hypervariable region) accounts for strain-specific epitopes (3,4,6,9,14,22,23). The molecular epidemiology and evolutionary patterns of G protein have provided important information about the clinical and epidemiological features of RSV: several different genotypes cocirculate, and the one that predominates in a community every year may change (5,21,22,28). However, the importance of strain diversity to the clinical and epidemiological features of RSV has yet to be elucidated in detail.Our objectives in the present study were to clarify the molecular epidemiology of RSV in a community over three seasons, determine the relationship between genotypes and circulation patterns, and assess clinical features and repeated infections. MATERIALS AND METHODSStudy population and clinical samples. The study was conducted over three seasons from

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In two influenza seasons during which H1N1 and H3N2 cocirculated, resistance was more frequent in H3N2 strains than in H1N1 strains after amantadine treatment. Predominant amino acid substitutions in M2 protein occurred at position 31 (serine to asparagine) in H3N2 strains and at position 27 (valine to alanine) in H1N1 strains.

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The 42-mer amyloid β-protein (Aβ42) aggregates to form soluble oligomers that cause memory loss and synaptotoxicity in Alzheimer's disease (AD). Oxidative stress is closely related to the pathogenesis of AD. We previously identified the toxic conformer of Aβ42 with a turn at positions 22 and 23 ("toxic turn") by solid-state NMR and demonstrated that a monoclonal antibody (11A1) against the toxic turn in Aβ42 mainly detected the oligomer in the brains of AD patients. Our recent study suggested that oxidative stress is a key factor of the oligomerization and cognitive impairment induced by Aβ overproduction in vivo. However, the involvement of the toxic conformer in Aβ42-induced oxidative damage remains unclear. To investigate this mechanism, we examined the levels of intracellular reactive oxygen species (ROS) and neurotoxicity in rat primary neurons using E22P-Aβ42, a mutant that induces a turn at positions 22 and 23, and E22V-Aβ42, a turn-preventing mutant. E22P-Aβ42, but not E22V-Aβ42, induced greater ROS production than Wt-Aβ42 in addition to potent neurotoxicity. Interestingly, the formation of the toxic conformer in both E22P-Aβ42 and Wt-Aβ42 probed by the 11A1 antibody preceded Aβ42-induced neurotoxicity. Trolox (a radical scavenger) and Congo red (an aggregation inhibitor) significantly prevented the neurotoxicity and intracellular ROS induced by E22P-Aβ42 and Wt-Aβ42, respectively. These results suggest that Aβ42-mediated toxicity is caused by the turn that favors toxic oligomers, which increase generation of ROS.

Oseltamivir has been used for treatment of infl uenza A and B infections, but recent reports documented that it was less active against the latter. We compared the effectiveness of oseltamivir in children between laboratory confi rmed infl uenza A and B over 4 infl uenza seasons from 2001 to 2005 in a pediatric clinic in Japan. Among 1,848 patients screened, 299 infl uenza A and 209 infl uenza B patients were administered oseltamivir (treated groups), and 28 infl uenza A and 66 infl uenza B patients were assigned as non-treated groups. The duration of fever, defi ned as period when patients had the maximum temperature higher than 37.5°C in three-time measurements in a day after the clinic visit, was evaluated among the four groups. In uni-variate analysis, the duration of fever was shorter for treated group than non-treated for infl uenza A (1.8 ± 0.9 days vs 2.6 ± 1.3 days, p < 0.01), but it was not signifi cant for infl uenza B (2.4 ± 1.3 days vs 2.8 ± 1.2 days, p = 0.9). The fever duration was longer in treated infl uenza B than A patients ( p < 0.01). Multi-variate analysis indicated younger age ( < 6 years old) and higher body temperature at the clinic visit prolonged the duration of fever. Adjusted average duration of fever indicated that oseltamivir was effective for both types, but more effective on infl uenza A, and the benefi t increased for younger children. Our data provide evidence that oseltamivir is benefi cial for infl uenza infections, but the effectiveness is differed by type and age. infl uenza; anti-viral drugs; oseltamivir; children; effectiveness.Tohoku

HMPV plays an important pathogenic role in patients with influenza-like illness in winter seasons, often in coinfections with influenza A viruses.