Interleukin-8 is the single most up-regulated gene in whole genome profiling of <Emphasis Type="Italic">H. pylori</Emphasis> exposed gastric epithelial cells

Background  

The association between Helicobacter pylori infection and upper gastrointestinal disease is well established. However, only a small fraction of H. pylori carriers develop disease, and there are great geographical differences in disease penetrance. The explanation to this enigma lies in the interaction between the bacterium and the host. H. pylori Outer Membrane Phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 h of H. pylori exposure, and to study the inflammatory response to OMPLA⁺ and OMPLA^- H. pylori variants.     

Selenium supplementation of lactating dairy cows: effects on milk production and total selenium content and speciation in blood, milk and cheese

Forty multiparous Holstein cows were used in a 16-week continuous design study to determine the effects of either selenium (Se) source, selenised yeast (SY) (derived from a specific strain of Saccharomyces cerevisiae CNCM I-3060) or sodium selenite (SS), or Se inclusion rate in the form of SY in the diets of lactating dairy cows on the Se concentration and speciation in blood, milk and cheese. Cows received ad libitum a total mixed ration (TMR) with a 1 : 1 forage : concentrate ratio on a dry matter (DM) basis. There were four diets (T1 to T4), which differed only in either source or dose of Se additive. Estimated total dietary Se for T1 (no supplement), T2 (SS), T3 (SY) and T4 (SY) was 0.16, 0.30, 0.30 and 0.45 mg/kg DM, respectively. Blood and milk samples were taken at 28-day intervals and at each time point there were positive linear effects of Se in the form of SY on the Se concentration in blood and milk. At day 112, blood and milk Se values for T1 to T4 were 177, 208, 248 and 279 ± 6.6 and 24, 38, 57 and 72 ± 3.7 ng/g fresh material, respectively, and indicate improved uptake and incorporation of Se from SY. In whole blood, selenocysteine (SeCys) was the main selenised amino acid and the concentration of selenomethionine (SeMet) increased with the increasing inclusion rate of SY. In milk, there were no marked treatment effects on the SeCys content, but Se source had a marked effect on the concentration of SeMet. At day 112, replacing SS (T2) with SY (T3) increased the SeMet concentration of milk from 36 to 111 ng Se/g and its concentration increased further to 157 ng Se/g dried sample as the inclusion rate of SY increased further (T4) to provide 0.45 mg Se/kg TMR. Neither Se source nor inclusion rate affected the keeping quality of milk. At day 112, milk from T1, T2 and T3 was made into a hard cheese and Se source had a marked effect on total Se and the concentration of total Se comprised as either SeMet or SeCys. Replacing SS (T2) with SY (T3) increased total Se, SeMet and SeCys content in cheese from 180 to 340 ng Se/g, 57 to 153 ng Se/g and 52 to 92 ng Se/g dried sample, respectively. The use of SY to produce food products with enhanced Se content as a means of meeting the Se requirements is discussed.     

A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods

Background

The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.

Methods

Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.

Findings

All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.

Conclusions

This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies.

Trial Registration

Controlled-Trials.com ISRCTN 30087513     

Rabbit and Nonhuman Primate Models of Toxin-Targeting Human Anthrax Vaccines

The intentional use of Bacillus anthracis, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. Biodefense vaccines are an important component of our arsenal to be used during a biological attack. However, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. As such, vaccine efficacy cannot be determined in human clinical trials but must be extrapolated from experimental animal models. This article reviews the efficacy and immunogenicity of human anthrax vaccines in well-defined animal models and the progress toward developing a rugged immunologic correlate of protection. The ongoing evaluation of human anthrax vaccines will be dependent on animal efficacy data in the absence of human efficacy data for licensure by the U.S. Food and Drug Administration.     

Synthesis and expression in Escherichia coli of DNA encoding the murine lambda 1 chain of a monoclonal antibody specific for Salmonella serotype B O-antigen.

A 658 bp DNA sequence corresponding to the murine lambda 1 chain of a monoclonal antibody, Se155-4, specific for the Salmonella serotype B O-antigen, was designed using Escherichia coli preferred codons and chemically synthesized by ligation of synthetic fragments into a linearized plasmid followed by transformation into E. coli. A synthetic signal peptide (ompA) was fused to express the L chain as a free polypeptide into the periplasm of E. coli cells. After isolation and purification, heterologous recombination of the E. coli L chain with mouse H chain gave an active antigen-binding protein. The activity was 15-20% when compared to protein created by an equivalent association of isolated natural mouse L and H chains as measured by a direct EIA assay. In inhibition experiments with the polysaccharide antigen, the two proteins showed identical titration curves and 50% inhibition points, indicating comparable KA values.     

Do Power Lines and Protected Areas Present a Catch-22 Situation for Cape Vultures (Gyps coprotheres)?

Cape vulture Gyps coprotheres populations have declined across their range due to multiple anthropogenic threats. Their susceptibility to fatal collisions with the expanding power line network and the prevalence of carcasses contaminated with illegal poisons and other threats outside protected areas are thought to be the primary drivers of declines in southern Africa. We used GPS-GSM units to track the movements and delineate the home ranges of five adult (mean ±SD minimum convex polygon area  =  121,655±90,845 km²) and four immature (mean ±SD minimum convex polygon area  =  492,300±259,427 km²) Cape vultures to investigate the influence of power lines and their use of protected areas. The vultures travelled more than 1,000 km from the capture site and collectively entered five different countries in southern Africa. Their movement patterns and core foraging ranges were closely associated with the spatial distribution of transmission power lines and we present evidence that the construction of power lines has allowed the species to extend its range to areas previously devoid of suitable perches. The distribution of locations of known Cape vulture mortalities caused by interactions with power lines corresponded to the core ranges of the tracked vultures. Although some of the vultures regularly roosted at breeding colonies located inside protected areas the majority of foraging activity took place on unprotected farmland. Their ability to travel vast distances very quickly and the high proportion of time they spend in the vicinity of power lines and outside protected areas make Cape vultures especially vulnerable to negative interactions with the expanding power line network and the full range of threats across the region. Co-ordinated cross-border conservation strategies beyond the protected area network will therefore be necessary to ensure the future survival of threatened vultures in Africa.