176 research outputs found

    Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells

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    <p>Abstract</p> <p>Background</p> <p>Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis), and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B) exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>). Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE) were used to comparatively assess silica particle-induced alterations in gene expression.</p> <p>Results</p> <p>Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75) and high (150 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>) amounts, respectively (p < 0.05/cut off ≥ 2.0-fold change). Exposure to amorphous silica micro-particles at high amounts (150 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>) induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p < 0.05) induced by crystalline silica, but none were induced by amorphous silica. QRT-PCR revealed that cristobalite selectively up-regulated stress-related genes and cytokines (<it>FOS, ATF3, IL6 </it>and <it>IL8</it>) early and over time (2, 4, 8, and 24 h). Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 10<sup>6</sup>μm<sup>2</sup>/cm<sup>2</sup>) revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells.</p> <p>Conclusions</p> <p>Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and/or metabolic activity is insufficient to predict their pathogenicity. Moreover, they show that acute responses of the lung epithelium, including up-regulation of genes linked to inflammation, oxidative stress, and proliferation, as well as secretion of inflammatory and proliferative mediators, can be indicative of pathologic potential using either immortalized lines (BEAS 2B) or primary cells (NHBE). Assessment of the degree and magnitude of these responses <it>in vitro </it>are suggested as predictive in determining the pathogenicity of potentially harmful particulates.</p

    Direct measurements of the effects of salt and surfactant on interaction forces between colloidal particles at water-oil interfaces

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    The forces between colloidal particles at a decane-water interface, in the presence of low concentrations of a monovalent salt (NaCl) and of the surfactant sodium dodecylsulfate (SDS) in the aqueous subphase, have been studied using laser tweezers. In the absence of electrolyte and surfactant, particle interactions exhibit a long-range repulsion, yet the variation of the interaction for different particle pairs is found to be considerable. Averaging over several particle pairs was hence found to be necessary to obtain reliable assessment of the effects of salt and surfactant. It has previously been suggested that the repulsion is consistent with electrostatic interactions between a small number of dissociated charges in the oil phase, leading to a decay with distance to the power -4 and an absence of any effect of electrolyte concentration. However, the present work demonstrates that increasing the electrolyte concentration does yield, on average, a reduction of the magnitude of the interaction force with electrolyte concentration. This implies that charges on the water side also contribute significantly to the electrostatic interactions. An increase in the concentration of SDS leads to a similar decrease of the interaction force. Moreover the repulsion at fixed SDS concentrations decreases over longer times. Finally, measurements of three-body interactions provide insight into the anisotropic nature of the interactions. The unique time-dependent and anisotropic interactions between particles at the oil-water interface allow tailoring of the aggregation kinetics and structure of the suspension structure.Comment: Submitted to Langmui

    Radiotherapy treatment planning of prostate cancer using magnetic resonance imaging

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    Purpose.-Magnetic resonance imaging (MRI) plays an increasing role in radiotherapy dose planning. Indeed, MRI offers superior soft tissue contrast compared to computerized tomography (CT) and therefore could provide a better delineation of target volumes and organs at risk than CT for radiotherapy. Furthermore, an MRI-only radiotherapy workflow would suppress registration errors inherent to the registration of MRI with CT. However, the estimation of the electronic density of tissues using MRI images is still a challenging issue. The purpose of this work was to design and evaluate a pseudo-CT generation method for prostate cancer treatments. Materials and methods.-A pseudo-CT was generated for ten prostate cancer patients using an elastic deformation based method. For each patient, dose delivered to the patient was calculated using both the planning CT and the pseudo-CT. Dose differences between CT and pseudo-CT were investigated. Results.-Mean dose relative difference in the planning target volume is 0.9% on average and ranges from 0.1% to 1.7%. In organs at risks, this value is 1.8%, 0.8%, 0.8% and 1% on average in the rectum, the right and left femoral heads, and the bladder respectively. Conclusio.-The dose calculated using the pseudo-CT is very close to the dose calculated using the CT for both organs at risk and PTV. These results confirm that pseudo-CT images generated using the proposed method could be used to calculate radiotherapy treatment doses on MRI images. (C) 2019 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.Peer reviewe

    Particularized protection: UNSC mandates and the protection of civilians in armed conflict

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    The protection of civilians at risk in armed conflict has, since the late 1990s, become institutionalized at the United Nations (UN), gaining acceptance as a normative rationale for UN peacekeeping. However, the bulk of civilians in need of protection in armed conflict are unlikely to attain it. The article develops an argument on ‘particularized protection’ - particularized in that UN Security Council (SC) mandates are formulated and adjusted over time to direct mission protection to specific subsets of civilian populations, that is, those relevant to the UN itself, the host state, other states, NGOs and the media, leaving most local civilians receiving little effective protection. Particularized protection, we argue, is a result of the institutional dynamics involving actors producing mandates - the UNSC - and those providing protection - peacekeeping missions - whereby mandates are specified to direct mission protection to selected, particularized groups. We demonstrate these dynamics in two cases, Côte d’Ivoire and Somalia

    New Insight into the Antifibrotic Effects of Praziquantel on Mice in Infection with Schistosoma japonicum

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    Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required.-induced liver fibrosis was inhibited by PZQ treatment for 30 days. Furthermore, we analyzed the effects of praziquantel on mouse primary hepatic stellate cells (HSCs). It is indicated that mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9 and TIMP1 of HSCs were all inhibited after praziquantel anti-parasite treatments.The significant amelioration of hepatic fibrosis by praziquantel treatment validates it as a promising drug of anti-fibrosis and offers potential of a new chemotherapy for hepatic fibrosis resulting from schistosomiasis
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