Multi-function oxidases are responsible for the synergistic interactions occurring between repellents and insecticides in mosquitoes

Background: With the spread of pyrethroid resistance in mosquitoes, the combination of an insecticide (carbamate or organophosphate) with a repellent (DEET) is considered as a promising alternative strategy for the treatment of mosquito nets and other relevant materials. The efficacy of these mixtures comes from the fact that they reproduce pyrethroid features and that positive interactions occur between insecticides and repellent. To better understand the mechanisms involved and assess the impact of detoxifying enzymes (oxidases and esterases) in these interactions, bioassays were carried out in the laboratory against the main dengue vector Aedes aegypti. Methods: Topical applications of DEET and propoxur (carbamate), used alone or as a mixture, were carried out on female mosquitoes, using inhibitors of the two main detoxification pathways in the insect. PBO, an inhibitor of multi-function oxidases, and DEF, an inhibitor of esterases, were applied one hour prior to the main treatment. Results: Results showed that synergism between DEET and propoxur disappeared in the presence of PBO but not with DEF. This suggests that oxidases, contrary to esterases, play a key role in the interactions occurring between DEET and cholinesterase inhibitors in mosquitoes. Conclusion: These findings are of great interest for the implementation of "combination nets" in the field. They support the need to combine insecticide with repellent to overcome insecticide resistance in mosquitoes of public health importance.

Rats, floods and flowers: London's Gothicized nature

AUTHOR's OVERVIEW This chapter attempts a definition of London eco-gothic, beginning with an ecocritical reading of the ubiquitous London rat. Following Dracula, popular London gothic has been overrun, from the blunt horror-schlock of James Herbert’s 1970s Rats series to China Miéville’s King Rat. Maud Ellman’s elegant discussion of the modernist rat as a protean figure associated with a ‘panoply of fears and fetishes’, underlines how the rat has always featured in anti-urban discourse: as part of racist representations of immigration; as an expression of fear of disease and poverty; or through a quasi-supernatural anxiety about their indestructible and illimitable nature which makes them a staple feature of post-apocalyptic landscapes. Even so, the London rat is a rather more mundane manifestation of urban eco-gothic than the ‘city wilderness’ metaphors common to representations of New York or Los Angles as identified by eco-critic Andrew White. London’s gothic noses its way out through cracks in the pavements, grows from seeds in suburban gardens or accumulates through the steady drip of rainwater. However, I will suggest, in texts such as Maggie Gee’s The Flood and P. D. James’ Children of Men, London eco-gothic becomes less local and familiar as it responds to global environmental crisis with more dramatic tales of minatorial nature.

Conference report: 7th Annual Congress of International Drug Discovery Science and Technology

This is a report on the 7th Annual Congress of International Drug Discovery Science and Technology held in Shanghai, China from 22–25 October, 2009. The conference, organized by BIT Life Sciences, comprised several parallel sessions, keynote presentations and a selection of selection of 20-minute presentations covering a range of therapeutic areas, including general medicinal chemistry, oncology, inflammation, receptors and ion channels, drug, metabolism and pharmokinetics, and fragment-based drug discovery. There were also sessions devoted to genomics, biomarkers, immunology, cell biology, molecular imaging and biochips. Supported by an exhibition of services/products and posters, the conference underlined the marked presence of Asian CROs.