UK-1

The initial virulence and invasiveness of a bacterial strain may play an important role in leading to a maximally efficacious attenuated live vaccine. Here we show that χ9909, derived from Salmonella Typhimurium UK-1 χ3761 (the most virulent S. Typhimurium strain known to us), is effective in protecting mice against lethal UK-1 and 14028S (less virulent S. Typhimurium strain) challenge. As opposed to this, 14028S-derived vaccine χ12359 induces suboptimal levels of protection, with survival percentages that are significantly lower when challenged with lethal UK-1 challenge doses. T-cell assays have revealed that significantly greater levels of Th1 cytokines IFN-γ and TNF-α were secreted by stimulated T-lymphocytes obtained from UK-1(ΔaroA) immunized mice than those from mice immunized with 14028S(ΔaroA). In addition, UK-1(ΔaroA) showed markedly higher colonizing ability in the spleen, liver, and cecum when compared to 14028S(ΔaroA). Enumeration of bacteria in fecal pellets has also revealed that UK-1(ΔaroA) can persist in the host for over 10 days whereas 14028S(ΔaroA) titers dropped significantly by day 10. Moreover, co-infection of parent strains UK-1 and 14028S resulted in considerably greater recovery of the former in multiple mucosal and gut associated lymphatic tissues. Mice immunized with UK-1(ΔaroA) were also able to clear UK-1 infection remarkably more efficiently from the target organs than 14028S(ΔaroA). Together, these results provide ample evidence to support the hypothesis that attenuated derivatives of parent strains with higher initial virulence make better vaccines.

The recent AstraZeneca takeover bid from Pfizer puts pharmaceutical R&D once again on the public agenda. Three pertinent questions are (a) what can be expected from this acquisition, (b) what are the implications for the UK economy and science base, and (c) whether such a deal should go ahead. Although the key driver behind this acquisition would be an improvement in company performance and shareholder value, past evidence suggests that mergers and acquisitions (M&A) of large pharmaceutical companies imply a neutral net effect on productivity, if not a decline, with employment decreasing and R&D spend following a similar trend. Similarities between the two companies include dropping sales; however, relative to its size, AstraZeneca has a more promising R&D pipeline, especially in therapeutic areas where Pfizer's strength is currently limited (e.g. oncology). Ensuring a portfolio diversification would make Pfizer's takeover proposal a knight's one, but history points towards a knave-like behavior.

This paper assesses the current knowledge of 1,3-butadiene as an atmospheric pollutant, considers measurement techniques and reviews available data on 1,3-butadiene monitoring and emissions estimates. Atmospheric chemistry, sources of emission, current legislation, measurement techniques and monitoring programmes for 1,3-butadiene are reviewed. There have been comparatively few studies of the products of oxidation of 1,3-butadiene in the atmosphere. However, on the basis of the available information, and by analogy with the oxidation mechanism for the widely-studied and structurally similar natural hydrocarbon isoprene (2-methyl-1,3-butadiene), it is possible to define some features of the likely oxidation pathways for 1,3-butadiene. The total UK 1,3-butadiene emission to the atmosphere for 1996 has been estimated at 10.60 kTonnes. 1,3-Butadiene is a product of petrol and diesel combustion; consequently this total is dominated by road transport exhaust emissions (accounting for some 68% of the total). Off-road vehicles and machinery are responsible for 14% of the total UK emission. 1,3-Butadiene is used in the manufacture of numerous rubber compounds, and consequently emissions arise from both the manufacture and use of 1,3-butadiene in industrial processes. Emissions from the chemical industry account for 18% of the UK total emission- 8% from 1,3-butadiene manufacture and 10% from 1,3-butadiene use. The United Kingdom Expert Panel on Air Quality Standards (EPAQS) has published a report on 1,3-butadiene, and recommended a national air quality standard of 1.0 ppb (expressed as an annual rolling mean). This was adopted by the Government as part of the National Air Quality Strategy (NAQS) in 1997, and a target of compliance by 2005 was set. Work conducted for the review of the NAQS (1999) indicated that it was likely that all locations would be compliant with the national standard by the end of 2003. As a result, the review updated the air quality objective for 1,3-butadiene, with the deadline for compliance being brought forward to 31/12/2003. The UK Hydrocarbon Monitoring Network provides continuous hourly measurements of 1,3-butadiene at 13 sites, and has been operational since 1993. The dataset that is available allows spatial and temporal trends to be evaluated, and has proved to be invaluable in characterising the current ambient levels of 1,3-butadiene in the UK. Hourly maximum concentrations of 1,3-butadiene of up to 10 ppb (1 ppb=1 ppb, i.e. 1 vol. of 1,3-butadiene in 1,000,000,000 vol. of air. 1 ppb of 1,3-butadiene is ca. equal to 2.25 microg m(-3) at 20 degrees C) may be measured for several hours at the sites. Monthly mean concentrations are typically 0.1-0.4 ppbv. At most sites, these levels are driven by emissions from motor vehicles. Occasionally emissions of 1,3-butadiene from industrial sources may elevate 1,3-butadiene concentrations to several tens of ppb. Trend analysis of the data suggests that ambient concentrations of 1,3-butadiene in the UK are declining at about 10% per year.