Putting jet lag to rest

Sildenafil, the active component of the erectile dysfunction drug Viagra, can attenuate the effects of circadian phase advances in hamsters. The new research from Diego A. Golombek and colleagues of the National University of Quilmes (Buenos Aires, Argentina) suggests that sildenafil may have potential as a treatment for jet lag and other circadian adaptation problems in humans.

Sildenafil inhibits the breakdown of cGMP and enhances the effects of the cGMP pathway, which is involved in phase-advancing mechanisms. Golombek treated male hamsters with sildenafil and then subjected them to a 6-hour advance of the light-dark cycle, roughly equivalent to an eastbound trans-Atlantic flight. Treated hamsters adjusted to the new light cycle more quickly than untreated hamsters, and the acceleration of cycle entrainment was dose-dependent. At an intermediate dose of 3.5 mg sildenafil per kg body weight given by intraperitoneal injection (a dose that was non-erectogenic), resynchronization time was shortened by 4 days compared with no treatment (Proc. Natl. Acad. Sci. USA, doi:10.1073/pnas.0703388104, published online 22 May).

If sildenafil can similarly mediate circadian adaptation in humans, it might hold promise for treating not only jet lag but also disturbances related to shift work and sleep-wake cycle maladjustments, opening up a whole new application for Viagra.

Antibodies against avian flu

With the threat of an avian flu pandemic lingering, the search for agents with prophylactic or therapeutic potential continues. Now, Antonio Lanzavecchia (Institute for Research in Biomedicine, Switzerland), Kanta Subbarao (National Institutes of Health, Bethesda, MD), and colleagues report that neutralizing antibodies from humans who had recovered from avian flu (H5N1) protected mice against H5N1 infection.

The researchers isolated immune cells from four individuals who had survived H5N1 infection and purified monoclonal antibodies from the cells. They then selected four antibodies that neutralized H5N1 in vitro. These four antibodies neutralized closely related H5N1 viruses as well as an H5N1 virus from a different lineage. When the researchers tested the antibodies in vivo, they protected mice from infection with the original virus when given 1 day before or 1–3 days after virus exposure (PLoS Med., May). Three of the antibodies also protected mice against infection by H5N1 from a different lineage. Treatment with the antibodies limited viral replication, minimized viral-induced lung damage, and prevented dissemination of the virus outside the lungs.

By showing that neutralizing antibodies derived from the blood of H5N1 survivors effectively prevent H5N1 infection in mice, Lanzavecchia and Subbarao present a new avenue of investigation for avian flu treatment.

Permanent ban on breeding government chimpanzees

The National Center for Research Resources (NCRR), part of the National Institutes of Health, has permanently ended its breeding program for chimpanzees used in research, citing concern about the prodigious funding required to care for such chimpanzees throughout their lives.

The breeding of chimpanzees owned or supported by the NCRR has been suspended since 1995, though animals bred or obtained before that time continue to be used in research laboratories across the US. Currently, an estimated 1,000–1,300 chimpanzees are used for research in the US, approximately 500 of which are owned by the NCRR. Another 90 NCRR chimpanzees are 'retired' from research and living in a federal sanctuary. Care for a single chimpanzee can cost as much as $500,000 over the 50 or more years that these apes can live, a significant investiture of funds that has led the NCRR to put a permanent end to its breeding program. The announcement does not affect NCRR chimpanzees currently involved in research. Despite the ban on chimpanzee breeding, in a statement on its website the NCRR reaffirmed its support for humane biomedical investigation using chimpanzees.