Exposure to Candida albicans Polarizes a T-Cell Driven Arthritis Model towards Th17 Responses, Resulting in a More Destructive Arthritis

BACKGROUND: Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis. METHODOLOGY: Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry. PRINCIPAL FINDINGS: Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and RORgammaT. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-gamma. CONCLUSION: This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype

Nano to microlevel modeling of cement-based materials

Synopsis: Recent developments in nanotechnology paved the way for deepening the modeling level of science-based kernels and enabling new opportunities in terms of understanding the formation of hydration products and their contribution to the microstructure. Based on these developments next generation models are considered to have the potential to design new advanced materials that contribute to sustainable construction. One of the activities currently running in this field is the Codice (Computationally Driven design of Innovative CEment-based materials) project which is a multi-scale modeling research project established within the European research arena FP7. The project has the ambition to bridge the nanoscale to the microscale by applying advanced computational simulation modeling techniques for cementitious materials. Nano-based models will be connected to the microscale level within the framework of the Hymostruc model. It is the objective of the CODICE project to provide more insight into the role of the fundamental building blocks of CSH gel (basically 5nm sized nanoparticles) and the mechanisms that govern their aggregation into high-density (HD) and low-density (LD) C-S-H varieties. Thus, the project aims to refine the microstructure of the Hymostruc model (Breugel 1991) so as to recognize the two types of C-S-H aggregates. The new computational scheme is expected to be a perfect tool to design new cementitious materials with improved mechanical properties.Peer reviewe

Il progetto EnCoRe: una iniziativa sovranazionale per promuovere il concetto di sostenibilità del calcestruzzo e dei materiali cementizi

Environmental issues are getting more and more relevant in several fields of human activities and the building industry is fully concerned by these concerns. Recycled concrete aggregates (RCA) can be produced by existing concrete members resulting by either industrial processes (i.e., precast structures) or demolitions of existing structures as a whole. Moreover, waste resulting from industrial processes other than the building industry (i.e., production of steel, management of glass, powders resulting from other depuration processes) could be efficiently disposed as concrete aggregates or employed as reinforcement for Fiber-Reinforced Concretes (FRC). The use of natural fibres can also result into an environmentally-friendly and cost-effective solution, especially in developing countries, because of the local availability of raw materials. In order to promote the use of concretes with recycled and/or natural constituents as construction materials, the compatibility between the non conventional constituents and the concrete matrix have to be deeply investigated and correlated to the resulting mechanical and durability properties of the composite. This is the main goal of the EnCoRe Project (www.encore-fp7.unisa.it), a EU-funded initiative, whose activities and main findings will be summarized in this paper

Psychological therapies for people with bipolar disorder: where are we now, and what is next?: ISBD Psychological Interventions Taskforce—Position paper

Health and Well-bein

High LDL levels lessen bone destruction during antigen-induced arthritis by inhibiting osteoclast formation and function

Contains fulltext : 214460.pdf (publisher's version ) (Closed access

High LDL-C levels attenuate onset of inflammation and cartilage destruction in antigen-induced arthritis

Item does not contain fulltextOBJECTIVES: In this study, we used hypercholesterolaemic apolipoprotein E-deficient (Apoe-/-) mice to investigate LDL/oxLDL effect on synovial inflammation and cartilage destruction during antigen-induced arthritis (AIA). Further, as macrophage FcgammaRs are crucial to immune complex-mediated AIA, we investigated in vitro the effects of high cholesterol levels on the expression of FcgammaRs on macrophages. METHODS: AIA was induced by intra-articular injection of mBSA into knee joints of immunised Apoe-/- and wild type (WT) control mice. Joint swelling was measured by uptake of 99mTc pertechnetate (99mTc). Joint inflammation and cartilage destruction were assessed by histology. Anti-mBSA IgGs were measured by ELISA and specific T-cell response by lymphocyte stimulation test. Upon oxLDL stimulation of WT macrophages, protein levels of FcgammaRs were measured by flow cytometry. RESULTS: Local induction of AIA resulted in less joint swelling, synovial infiltrate and exudate in the joint cavity in Apoe-/- mice compared to WT controls, even though both their humoral and adaptive immune response were comparable. Whereas Apoe deficiency alone did not affect macrophage expression of FcgammaRs, oxLDL sharply reduced the protein levels of activating FcgammaRs, crucial in mediating cartilage damage. In agreement with the reduced inflammation in Apoe-/- mice, we observed decreased MMP activity and destruction in the articular cartilage. CONCLUSIONS: Taken together, our findings suggest that high levels of LDL/oxLDL during inflammation, dampen the initiation and chronicity of joint inflammation and cartilage destruction in AIA by regulating macrophage FcgammaR expression

High LDL-C levels attenuate onset of inflammation and cartilage destruction in antigen-induced arthritis

OBJECTIVES: In this study, we used hypercholesterolaemic apolipoprotein E-deficient (Apoe-/-) mice to investigate LDL/oxLDL effect on synovial inflammation and cartilage destruction during antigen-induced arthritis (AIA). Further, as macrophage FcgammaRs are crucial to immune complex-mediated AIA, we investigated in vitro the effects of high cholesterol levels on the expression of FcgammaRs on macrophages. METHODS: AIA was induced by intra-articular injection of mBSA into knee joints of immunised Apoe-/- and wild type (WT) control mice. Joint swelling was measured by uptake of 99mTc pertechnetate (99mTc). Joint inflammation and cartilage destruction were assessed by histology. Anti-mBSA IgGs were measured by ELISA and specific T-cell response by lymphocyte stimulation test. Upon oxLDL stimulation of WT macrophages, protein levels of FcgammaRs were measured by flow cytometry. RESULTS: Local induction of AIA resulted in less joint swelling, synovial infiltrate and exudate in the joint cavity in Apoe-/- mice compared to WT controls, even though both their humoral and adaptive immune response were comparable. Whereas Apoe deficiency alone did not affect macrophage expression of FcgammaRs, oxLDL sharply reduced the protein levels of activating FcgammaRs, crucial in mediating cartilage damage. In agreement with the reduced inflammation in Apoe-/- mice, we observed decreased MMP activity and destruction in the articular cartilage. CONCLUSIONS: Taken together, our findings suggest that high levels of LDL/oxLDL during inflammation, dampen the initiation and chronicity of joint inflammation and cartilage destruction in AIA by regulating macrophage FcgammaR expression

Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1.

Contains fulltext : 47662.pdf (publisher's version ) (Closed access)Rheumatoid arthritis is characterized by an intermittent course of disease with alternate periods of remission and relapse. T cells, and in particular the T-cell cytokine interleukin-17 (IL-17), are expected to be involved in arthritic flares. Here, we report that neutralizing endogenous IL-17 during reactivation of antigen-induced arthritis prevents joint inflammation and bone erosion. Synovial IL-17 mRNA expression was clearly up-regulated during primary arthritis and was further enhanced after antigen rechallenge. Neutralization of IL-17 significantly prevented joint swelling at day 1 of flare and significantly suppressed joint inflammation and cartilage proteoglycan depletion at day 4, as assessed by histology. Blocking IL-17 also clearly reduced bone erosions. Cathepsin K, a marker of osteoclast-like activity, and synovial RANKL mRNA expression were both suppressed. The degree of bone erosions strongly correlated with the severity of joint inflammation, suggesting that anti-IL-17 treatment reduced bone erosion by suppressing joint inflammation. Interestingly, blocking IL-17 suppressed synovial expression of both IL-1beta and tumor necrosis factor-alpha, whereas blocking IL-1 did not affect tumor necrosis factor-alpha levels. These data indicate that IL-17 is an important upstream mediator in joint pathology during flare-up of experimental arthritis