A novel adjuvant–allergen complex, CBP–rFel d 1, induces up-regulation of CD86 expression and enhances cytokine release by human dendritic cells in vitro

Allergen-specific immunotherapy is commonly performed with allergen extracts adsorbed to aluminium hydroxide (alum). The undesirable effects associated with the use of alum, including granuloma formation at the site of injection and stimulation of T helper 2 (Th2) cytokine production, has generated interest in alternative allergen carriers, one being carbohydrate-based particles (CBPs). Here, we have investigated the in vitro effects of the recombinant major cat allergen Fel d 1 (rFel d 1) coupled to CBPs (CBP–rFel d 1) on human monocyte-derived dendritic cells (MDDCs) obtained from healthy blood donors. A majority of the CD1a(+) MDDCs internalized fluorescein isothiocyanate-labelled CBP–rFel d 1, as demonstrated by flow cytometry and confocal laser-scanning microscopy. Furthermore, an up-regulation of the expression of the costimulatory molecule, CD86, on the MDDCs was induced by CBP–rFel d 1, but not by rFel d 1 or CBPs alone. Finally, three- and fourfold increases in the release of interleukin-8 and tumour necrosis factor-α, respectively, were observed when MDDCs were cultured in the presence of CBP-rFel d 1. Altogether, our results indicate that the use of CBPs as an allergen carrier and adjuvant is a promising candidate for the improvement of allergen-specific immunotherapy

KomNet. Part: SmartModem: Advanced xDSL Technology for QoS Final report

SIGLEAvailable from TIB Hannover: F03B1596 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10(-/-)) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor.Mucosal Immunology advance online publication, 16 October 2013; doi:10.1038/mi.2013.78

Monolithic scintillator PET detectors with intrinsic depth-of-interaction correction

We developed positron emission tomography (PET) detectors based on monolithic scintillation crystals and position-sensitive light sensors. Intrinsic depth-of-interaction (DOI) correction is achieved by deriving the entry points of annihilation photons on the front surface of the crystal from the light sensor signals. Here we characterize the next generation of these detectors, consisting of a 20 mm thick rectangular or trapezoidal LYSO:Ce crystal read out on the front and the back (double-sided readout, DSR) by Hamamatsu S8550SPL avalanche photodiode (APD) arrays optimized for DSR. The full width at half maximum (FWHM) of the detector point-spread function (PSF) obtained with a rectangular crystal at normal incidence equals ~1.05 mm at the detector centre, after correction for the ~0.9 mm diameter test beam of annihilation photons. Resolution losses of several tenths of a mm occur near the crystal edges. Furthermore, trapezoidal crystals perform almost equally well as rectangular ones, while improving system sensitivity. Due to the highly accurate DOI correction of all detectors, the spatial resolution remains essentially constant for angles of incidence of up to at least 30°. Energy resolutions of ~11% FWHM are measured, with a fraction of events of up to 75% in the full-energy peak. The coincidence timing resolution is estimated to be 2.8 ns FWHM. The good spatial, energy and timing resolutions, together with the excellent DOI correction and high detection efficiency of our detectors, are expected to facilitate high and uniform PET system resolution.RRR/Radiation, Radionuclides and ReactorsApplied Science