A novel TLR2 agonist from Bordetella pertussis is a potent adjuvant that promotes protective immunity with an acellular pertussis vaccine.

Bordetella pertussis causes whooping cough, a severe and often lethal respiratory infection in infants. A recent resurgence of pertussis has been linked with waning or suboptimal immunity induced with acellular pertussis vaccines (Pa) that were introduced to most developed countries in the 1990s because of safety concerns around the use of whole-cell pertussis vaccines (Pw). Pa are composed of individual B. pertussis antigens absorbed to alum and promote strong antibody, T helper type 2 (Th2) and Th17 responses, but are less effective at inducing cellular immunity mediated by Th1 cells. In contrast, Pw, which include endogenous Toll-like receptor (TLR) agonists, induce Th1 as well as Th17 responses. Here we report the identification and characterization of novel TLR2-activating lipoproteins from B. pertussis. These proteins contain a characteristic N-terminal signal peptide that is unique to Gram-negative bacteria and we demonstrate that one of these lipoproteins, BP1569, activates murine dendritic cells and macrophages and human mononuclear cells via TLR2. Furthermore, we demonstrated that a corresponding synthetic lipopeptide LP1569 has potent immunostimulatory and adjuvant properties, capable of enhancing Th1, Th17, and IgG2a antibody responses induced in mice with an experimental Pa that conferred superior protection against B. pertussis infection than an equivalent vaccine formulated with alum.

Immunity to the respiratory pathogen Bordetella pertussis.

Bordetella pertussis causes whooping cough, a severe respiratory tract infection in infants and children, and also infects adults. Studies in murine models have shown that innate immune mechanisms involving dendritic cells, macrophages, neutrophils, natural killer cells, and antimicrobial peptides help to control the infection, while complete bacterial clearance requires cellular immunity mediated by T-helper type 1 (Th1) and Th17 cells. Whole cell pertussis vaccines (wP) are effective, but reactogenic, and have been replaced in most developed countries by acellular pertussis vaccines (aP). However, the incidence of pertussis is still high in many vaccinated populations; this may reflect sub-optimal, waning, or escape from immunity induced by current aP. Protective immunity generated by wP appears to be mediated largely by Th1 cells, whereas less efficacious alum-adjuvanted aP induce strong antibody Th2 and Th17 responses. New generation aP that induce Th1 rather than Th2 responses are required to improve vaccine efficacy and prevent further spread of B. pertussis.

The in vitro effects of tricyclic drugs and dexamethasone on cellular respiration of malignant glioma.

BACKGROUND: In this investigation the effects of tricyclic drugs on cellular respiration were studied using the anaplastic astrocytoma cell line IPSB-18 by use of a Clark-type oxygen electrode which measured changes in cellular respiration rate (oxygen consumption), in a dose-response assay. MATERIALS AND METHODS: The drugs investigated were clomipramine, norclomipramine, amitriptyline and doxepin. In addition, the combined effects of dexamethasone and clomipramine on cellular respiration were investigated. RESULTS: It was established that at lower concentrations (0.14 mM-0.5 mM) amitriptyline was the most potent inhibitor of cellular respiration. Previous studies have indicated that inhibition of cellular respiration is considered an indicator of apoptosis. Overall, it appeared that clomipramine and its metabolite norclomipramine were the most potent inhibitors of cellular respiration in glioma cells over the concentration range 0.5-0.9 mM. Dexamethasone was able to induce inhibition of cellular respiration both alone in glioma cells, and in combination with clomipramine, where it had an additive or synergistic effect, thereby increasing cell death. CONCLUSION: The extensive research currently ongoing and previously reported regarding the use of clomipramine as a potential antineoplastic agent aimed at targeting the mitochondria of gliomas is promising.

Interaction of air ions and bactericidal vapours to control micro-organisms.

AIMS: The aim of this study was to investigate the antibacterial activity of candles containing specific-antibacterial compounds, such as essential oils and their constituent compounds. The importance of the ionization products from the flame and the aerial concentration of the volatile compounds were investigated. METHODS AND RESULTS: Agar plates inoculated with Escherichia coli (DH5alpha) or Staphylococcus aureus (NCTC strain number 8532) were exposed in a large air-tight chamber to candle flames combined with the volatile bactericidal compounds beta-pinene and orange oil. A steady decline in E. coli numbers was observed over time because of the effect of a candle flame. This was significantly increased by the addition of volatile oils. The number of S. aureus colonies was not reduced by a plain candle, but significant reductions were caused following exposure to beta-pinene and orange oil candles. As aerial concentration of the volatiles was increased the viability of E. coli and S. aureus declined. Ionization products from the flame made a significant contribution to the observed effects, as intercepting the ions on a grounded grid over the agar plates allowed at least 20% more cells to survive. CONCLUSIONS: This study demonstrates the antibacterial properties of ionization products from a candle flame, and that this effect can be significantly increased by the addition of specific-antibacterial compounds, such as orange oil and beta-pinene. The role of both the ionization products from the candle flame and the concentration of volatile compounds released are important to the effect. SIGNIFICANCE AND IMPACT OF THE STUDY: The technique described here offers a new and novel technique for reducing the concentration of bacteria on surfaces.

Electrogastrographic biofeedback: a technique for enhancing normal gastric activity.

Biofeedback has been used effectively for approximately 40 years as a technique to help individuals learn to control muscle activity, brain waves, certain autonomic nervous system responses such as heart rate and blood pressure, and, more recently, constipation and fecal and urinary incontinence. In the present study, biofeedback of electrogastrographic (EGG) activity was used to determine the extent to which healthy subjects could increase normal 3 cpm gastric myoelectric activity. Thirteen experimental participants were provided with biofeedback of their EGG activity on a computer screen, and instructed to try to make their own EGG signal match a simulated 3 cpm signal that was also present on the screen. Subjects were told to relax using various forms of imagery, and to heighten their awareness of their stomach activity. Thirteen control participants did not receive any biofeedback but were otherwise given the same instructions. Both groups showed an increase in 3 cpm activity while relaxing. However, over four trials separated by 2-7 days, experimental participants showed an increased percentage of 3 cpm activity during biofeedback sessions, while control participants showed a decrease in 3 cpm activity during the corresponding sessions. In conclusion, we have demonstrated that healthy subjects can increase their normal gastric 3 cpm activity with the use of EGG biofeedback.