Engineered amorphous silicananoparticles (SiO sub(2)-NPs) are widely used in dyes, varnishes, plastics and glue, as well as in pharmaceuticals, cosmetics and food. Novel composite SiO sub(2)-NPs are ...promising multifunctional devices and combine labels for subsequent tracking and are functionalized e.g. to specifically target cells to deliver their cargo. However, biological and potential toxic effects of SiO sub(2)-NPs are insufficiently understood. The aim of this study was to determine the uptake and fate of SiO sub(2)-NPs in mammalian cells. Also, silica submicron particles (SiO sub(2)-SMPs) were included in the studies in order to identify effects, which are only observed for nano-sized SiO sub(2) particles. Fluorescently labelled SiO sub(2)-NPs (nominal size 70nm) and SiO sub(2)-SMPs (nominal size 200 and 500nm) were used to examine cytotoxicity, cellular uptake and localization in human cervical carcinoma cells (HeLa). Particle uptake and intracellular localization in mitochondria, endosomes, lysosomes and nuclei were studied by wide field and confocal laser scanning fluorescence microscopy. Physicochemical characterization of SiO sub(2)-NPs by transmission electron microscopy and dynamic light scattering revealed a spherical morphology and a monodisperse size distribution. In the presence of serum, all SiO sub(2) particles are non-toxic. However, in the absence of serum SiO sub(2)-NPs but not SiO sub(2)-SMPs are highly toxic. SiO sub(2) particles, irrespective of size, were detected in the cytosol and accumulated in endosomal compartments of HeLa cells. No accumulation of SiO sub(2) particles in nuclei or mitochondria of HeLa cells could be observed. In contrast to SiO sub(2)-SMPs, SiO sub(2)-NPs are preferentially localized in lysosomes.
Fly ash from a municipal waste incinerator was used as a model for atmospheric particles in order to identify parameters relevant for the induction of adverse health effects. The aim of this study ...was to compare the biological effects of the total incinerator fly ash (IFA), the soluble and the insoluble fraction with the effects of quartz by in vitro toxicity studies. The previously sized fly ash (<20μm) was characterized by elemental composition and particle size distribution. The particles were administered to rat alveolar macrophages (NR8383) and human bronchial epithelial cells (BEAS-2B) at different amounts via the medium. The total IFA and its insoluble fraction were shown to induce cytotoxicity and cytokine release in a dose-dependent manner. The soluble fraction was nearly unable to induce cytotoxicity and TNF-α release but showed potent induction of IL-8 release in BEAS-2B cells at increasing concentrations. Quartz caused similar effects compared to IFA in NR8383 but was less effective in BEAS-2B.
Role of particle surface area on lipid metabolism and the impact of ambient particles like diesel exhaust particles (DEP) on toll-like receptor (TLR)-mediated responses in cellular models are ...discussed. Cellular systems allow studying mechanisms of oxidative stress as a major cause of particle toxicity. It is suggested that alveolar macrophages may play a major role in lung disorders such as in chronic obstructive pulmonary diseases (COPD). Particle surface area and the innate oxidative potential of ultrafine particle (UFP) appear to be critical parameters for initiating and directing inflammatory events on the level of lipid mediators. In an allergic animal model using OVA-sensitized and challenged mice, exposures to UFP lead not only to an increased recruitment of inflammatory cells to the lungs but also to alerted expression of gene involved in various physiological processes.
The fusion glycoprotein (F0) was isolated from Newcastle disease virus (NDV) particles metabolically labelled with 2‐3Hmannose; it was successively digested with protease and with ...endo‐β‐N‐acetylglucosaminidase from Streptomyces griseus. In this manner, the majority of the oligosaccharides in NDV F0 could be liberated. After reduction with NaBH4, they were separated by high‐performance liquid chromatography, and were subjected to structural analysis. Using micromethylation/capillary gas chromatography/mass fragmentography, α‐mannosidase digestion, and acetolysis, it was found that the enzymatically released NDV F0 oligosaccharides are common oligomannosidic glycoprotein glycans of size classes (Man)8GlcNAc, (Man)7GlcNAc, (Man)6GlcNAc, (Man)9GlcNAc, and (Man)5GlcNAc (in order of prevalence). The major structural isomers present in the NDV F0(Man)8GlcNAc to (Man)5GlcNAc fractions were shown to lack mannose residues D2, D1D2 or D2D3, D1D2D3, and CD1D2D3, respectively, of (Man)9GlcNAc:
Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first ...year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Objective Our objective was to assess the effect of mycobacterial disease in patients with CGD. Methods We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Results Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae , or Mycobacterium ulcerans . Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Conclusion Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.
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