Haemozoin Induces Early Cytokine-Mediated Lysozyme Release from Human Monocytes through p38 MAPK- and NF-kappaB- Dependent Mechanisms

Malarial pigment (natural haemozoin, HZ) is a ferriprotoporphyrin IX crystal produced by Plasmodium parasites after haemoglobin catabolism. HZ-fed human monocytes are functionally compromised, releasing increased amounts of pro-inflammatory molecules, including cytokines, chemokines and cytokine-related proteolytic enzyme Matrix Metalloproteinase-9 (MMP-9), whose role in complicated malaria has been recently suggested. In a previous work HZ was shown to induce through TNFalpha production the release of monocytic lysozyme, an enzyme stored in gelatinase granules with MMP-9. Here, the underlying mechanisms were investigated. Results showed that HZ lipid moiety promoted early but not late lysozyme release. HZ-dependent lysozyme induction was abrogated by anti-TNFalpha/IL-1 beta/MIP-1 alpha blocking antibodies and mimicked by recombinant cytokines. Moreover, HZ early activated either p38 MAPK or NF-kappaB pathways by inducing: p38 MAPK phosphorylation; cytosolic I-kappaB alpha phosphorylation and degradation; NF-kappaB nuclear translocation and DNA-binding. Inhibition of both routes through selected molecules (SB203580, quercetin, artemisinin, parthenolide) prevented HZ-dependent lysozyme release. These data suggest that HZ-triggered overproduction of TNFalpha, IL-1 beta and MIP-1 alpha mediates induction of lysozyme release from human monocytes through activation of p38 MAPK and NF-kappaB pathways, providing new evidence on mechanisms underlying the HZ-enhanced monocyte degranulation in falciparum malaria and the potential role for lysozyme as a new affordable marker in severe malaria

Feature-Based Modelling of Laryngoscope Blades for Customized Applications

AbstractLaryngoscopes are used as diagnostic devices for throat inspection or as an aid to intubation. Their blade must be geometrically compatible with patients' anatomy to provide a good view to doctors with minimal discomfort to patients. For this reason, this paper was aimed to investigate the feasibility of producing customized blades.The customizable blade model was developed following a feature-based approach with eight morphological parameters. The thickness of such a blade was determined through numerical simulations of ISO certification tests, where the finite element mesh was obtained by morphing a 'standard' mesh.The following procedure was applied: the model was built from the selected parameters; the blade was tested in silico; finally, the blade was produced by additive manufacturing with an innovative biodegradable material (Hemp Bio-Plastic® -HBP-) claimed to feature superior mechanical properties. The procedure evidenced that the mechanical properties of current biodegradable materials are unsuitable for the application unless the certification norm is revised, as it is expected

Effects of chrysotile exposure in human bronchial epithelial cells: Insights into the pathogenic mechanisms of asbestos-related diseases

BACKGROUND: Chrysotile asbestos accounts for > 90% of the asbestos used worldwide, and exposure is associated with asbestosis (asbestos-related fibrosis) and other malignancies; however, the molecular mechanisms involved are not fully understood. A common pathogenic mechanism for these malignancies is represented by epithelial–mesenchymal transition (EMT), through which epithelial cells undergo a morphological transformation to assume a mesenchymal phenotype. In the present work, we propose that chrysotile asbestos induces EMT through a mechanism involving a signaling pathway mediated by tranforming growth factor beta (TGF-β). OBJECTIVES: We investigated the role of chrysotile asbestos in inducing EMT in order to elucidate the molecular mechanisms involved in this event. METHODS: Human bronchial epithelial cells (BEAS-2B) were incubated with 1 μg/cm2 chrysotile asbestos for ≤ 72 hr, and several markers of EMT were investigated. Experiments with specific inhibitors for TGF-β, glycogen synthase kinase–3β (GSK-3β), and Akt were performed to confirm their involvement in asbestos-induced EMT. Real-time polymerase chain reaction (PCR), Western blotting, and gelatin zymography were performed to detect mRNA and protein level changes for these markers. RESULTS: Chrysotile asbestos activated a TGF-β–mediated signaling pathway, implicating the contributions of Akt, GSK-3β, and SNAIL-1. The activation of this pathway in BEAS-2B cells was associated with a decrease in epithelial markers (E-cadherin and β-catenin) and an increase in mesenchymal markers (α-smooth muscle actin, vimentin, metalloproteinases, and fibronectin). CONCLUSIONS: Our findings suggest that chrysotile asbestos induces EMT, a common event in asbestos-related diseases, at least in part by eliciting the TGF-β–mediated Akt/GSK-3β/SNAIL-1 pathway. CITATION: Gulino GR, Polimeni M, Prato M, Gazzano E, Kopecka J, Colombatto S, Ghigo D, Aldieri E. 2016. Effects of chrysotile exposure in human bronchial epithelial cells: insights into the pathogenic mechanisms of asbestos-related diseases. Environ Health Perspect 124:776–784; http://dx.doi.org/10.1289/ehp.140962

Ultra High Molecular Weight Polyethylene is Cytotoxic and Causes Oxidative Stress, Even When Modified:

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Additively manufactured custom load-bearing implantable devices

BackgroundAdditive manufacturing technologies are being enthusiastically adopted by the orthopaedic community since they are providing new perspectives and new possibilities. First applications were finalised for educational purposes, pre-operative planning, and design of surgical guides; recent applications also encompass the production of implantable devices where 3D printing can bring substantial benefits such as customization, optimization, and manufacturing of very complex geometries. The conceptual smoothness of the whole process may lead to the idea that any medical practitioner can use a 3D printer and her/his imagination to design and produce novel products for personal or commercial use.AimsOutlining how the whole process presents more than one critical aspects, still demanding further research in order to allow a safe application of this technology for fully-custom design, in particular confining attention to orthopaedic/orthodontic prostheses defined as components responding mainly to a structural function.Methods Current knowledge of mechanical properties of additively manufactured components has been examined along with reasons why the behaviour of these components might differ from traditionally manufactured components. The structural information still missing for mechanical design is outlined.Results Mechanical properties of additively manufactured components are not completely known, and especially fatigue limit needs to be examined further.ConclusionAt the present stage, with reference to load-bearing implants subjected to many loading cycles, the indication of custom-made additively manufactured medical devices should be restricted to the cases with no viable alternative