Avian influenza: genetic evolution under vaccination pressure.

Antigenic drift of avian influenza viruses (AIVs) has been observed in chickens after extended vaccination program, similar to those observed with human influenza viruses. To evaluate the evolutionary properties of endemic AIV under high vaccination pressure (around 2 billion doses used in the last 12 years), we performed a pilot phylogenic analysis of the hemagglutinin (HA) gene of AIVs isolated from 1994 to 2006. This study demonstrates that Mexican low pathogenicity (LP) H5N2-AIVs are constantly undergoing genetic drifts. Recent AIV isolates (2002-2006) show significant molecular drifts when compared with the H5N2 vaccine-strain or other field isolates (1994-2000). This study also demonstrates that molecular drifts in the HA gene lineages follow a yearly trend, suggesting gradually cumulative sequence mutations. These findings might explain the increasing incidence of LP H5N2 AIV isolated from commercial avian farms. These findings support recent concerns about the challenge of AIV antigenic drift and influenza epidemics.

Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms.

In this work, we investigated the effects of Casiopeina II-gly (Cas IIgly)--a new copper compound exhibiting antineoplastic activity--on glioma C6 cells under both in vitro and in vivo conditions, as an approach to identify potential therapeutic agents against malignant glioma. The exposure of C6 cells to Cas IIgly significantly inhibited cell proliferation, increased reactive oxygen species (ROS) formation, and induced apoptosis in a dose-dependent manner. In cultured C6 cells, Cas IIgly caused mitochondrio-nuclear translocation of apoptosis induction factor (AIF) and endonuclease G at all concentrations tested; in contrast, fragmentation of nucleosomal DNA, cytochrome c release, and caspase-3 activation were observed at high concentrations. Administration of N-acetyl-L-cystein, an antioxidant, resulted in significant inhibition of AIF translocation, nucleosomal DNA fragmentation, and caspase-3 activation induced by Cas IIgly. These results suggest that caspase-dependent and caspase-independent pathways both participate in apoptotic events elicited by Cas IIgly. ROS formation induced by Cas IIgly might also be involved in the mitochondrio-nuclear translocation of AIF and apoptosis. In addition, treatment of glioma C6-positive rats with Cas IIgly reduced tumor volume and mitotic and cell proliferation indexes, and increased apoptotic index. Our findings support the use of Cas IIgly for the treatment of malignant gliomas.