Annexin 1 localisation in tissue eosinophils as detected by electron microscopy.

BACKGROUND: Human and rodent leukocytes express high levels of the glucocorticoid-inducible protein annexin 1 (ANXA1) (previously referred to as lipocortin 1). Neutrophils and monocytes have abundant ANXA1 levels. AIM: We have investigated, for the first time, ANXA1 ultrastructural expression in rat eosinophils and compared it with that of extravasated neutrophils. The effect of inflammation (carrageenin peritonitis) was also monitored. METHODS: Electron microscopy was used to define the sub-cellular localisation of ANXA1 in rat eosinophils and neutrophils extravasated in the mesenteric tissue. A pair of antibodies raised against the ANXA1 N-terminus (i.e. able to recognise intact ANXA1, termed LCPS1) or the whole protein (termed LCS3) was used to perform the ultrastructural analysis. RESULTS: The majority of ANXA1 was localised in the eosinophil cytosol (approximately 60%) and nucleus (30-40%), whereas a small percentage was found on the plasma membrane (< 10%). Within the cytosol, the protein was equally distributed in the matrix and in the granules, including those containing the typical crystalloid. The two anti-ANXA1 antibodies gave similar results, with the exception that LCPS1 gave a lower degree of immunoreactivity in the plasma membrane. Inflammation (i.e. carrageenin injection) produced a modest increase in eosinophil-associated ANXA1 reactivity (significant only in the cytoplasm compartment). Extravasated neutrophils, used for comparative purposes, displayed a much higher degree of immunoreactivity for the protein. CONCLUSION: We describe for the first time ANXA1 distribution in rat eosinophil by ultrastructural analysis, and report a different protein mobilisation from extravasated neutrophils, at least in this acute model of peritonitis

The involvement of anti-inflammatory protein, Annexin A1, in ocular toxoplasmosis

Purpose: The aim of this study was to evaluate the expression of the protein annexin A1 (ANXA1), a potent endogenous regulator of the inflammatory process, in ocular toxoplasmosis. Methods: C57BL/6 female mice were infected using intravitreal injections of either 10 6 tachyzoites of Toxoplasma gondii (RH strain; T. gondii) or PBS only (control groups). After 24, 48, and 72 h, animals were sacrificed and their eyes were harvested for histopathological, immunohistochemical, and ultrastructural immunocytochemical analysis of ANXA1. Human retinal pigment epithelial (RPE) cells (ARPE-19) were infected in vitro with T. gondii and collected after 60, 120, 240 min, and 24 h. Results: Compared with non-infected eyes, an intense inflammatory response was observed in the anterior (24 h after infection) and posterior segments (72 h after infection) of the infected eye, characterized by neutrophil infiltration and by the presence of tachyzoites and their consequent destruction along with disorganization of normal retina architecture and RPE vacuolization. T. gondii infection was associated with a significant increase of ANXA1 expression in the neutrophils at 24, 48, and 72 h, and in the RPE at 48 and 72 h. In vitro studies confirmed an upregulation of ANXA1 levels in RPE cells, after 60 and 120 min of infection with T. gondii. Conclusions: The positive modulation of endogenous ANXA1 in the inflammatory and RPE cells during T. gondii infection suggests that this protein may serve as a therapeutic target in ocular toxoplasmosis. © 2012 Molecular Vision

A strategy for the robust forecasting of gas turbine health subjected to fouling

Fouling represents a major problem for Gas Turbines (GTs) in both heavy-duty and aeropropulsion applications. Solid particles entering the engine can stick to the internal surfaces and form deposits. Components' lifetime and performance can dramatically vary as a consequence of this phenomenon. These effects impact the whole engine in terms of residual life, operating stability, and maintenance costs. In the High-Pressure Turbine (HPT), in particular, the high temperatures soft the particles and promote their adhesion, especially in the short term. Unfortunately, predicting the GT response to this detrimental issue is still an open problem for scientists. Furthermore, the stochastic variations of the components operating conditions increase the uncertainty of the forecasting results. In this work, a strategy to predict the effects of turbine fouling on the whole engine is proposed. A stationary Gas Path Analysis (GPA) has been performed for this scope to predict the GT health parameters. Their alteration as a consequence of fouling has been evaluated by scaling the turbine map. The scaling factor has been found by performing Computational Fluid Dynamic (CFD) simulations of a HPT nozzle with particle injection. Being its operating conditions strongly uncertain, a stochastic analysis has been conducted. The uncertainty sources considered are the circumferential hot core location and the turbulence level at the inlet. The study enables to build of confidence intervals on the GT health parameters predictions and represents a step forward towards a robust forecasting tool

"Green oncology": a new paradigm for medical oncology

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Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine

Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. We aim systematically promote this intervention with all Lynch syndrome carriers

Off-line washing effectiveness on a multistage axial compressor

The interaction between gas turbines and airborne particles determines detrimental effects on the performance, efficiency, and reliability of the power unit. When it is possible, the interaction is reduced by the use of inlet separators and filtration systems. In an aero engine, these barriers are difficult to implement, and only bigger particles (usually greater than 10 µm) are separated from the airflow. Small units, especially those equips helicopters, are usually affected by fouling issues, especially when the aircraft is employed in harsh environments such as firefighting and rescue activities. To recover this contamination, the unit is washed after the mission by ground operations to restore the unit performance by removing the deposits. This operation occurs during a sub-idle unit operation, and the washing process has to be effective when the engine operates in this off-design condition. In this paper, the evaluation of the washing performance during a sub-idle unit operation is carried out. The compressor unit is a multistage axial compressor that equips the Allison 250-C18 engine. The washing operation was performed by water, and a sensitivity analysis is carried out to discover the capability of water droplets to remove the contaminants. The experimental analysis involves the contamination of the unit by micro-sized soot particles and a washing operation by micro-sized water droplets. These experimental results are compared to numerical simulations to discover the effects of the washing operation on a small power unit during sub-idle operating conditions. The off-design regime imposes a specific evaluation of the proper setup of the washing strategy: flow separations involve wider regions in the compressor unit, and the removal capability is strongly related to the droplet path through the stages. The results show how in the off-design washing operation, the droplet diameter has greater importance than the water flow rate for reducing the deposits over the compressor stages. © The Authors, published by EDP Sciences. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (http://creativecommons.org/licenses/by/4.0/

Style modification in breast and Colorectal Cancer Patients: results of a pilot study Long-Survivors

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Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: A retrospective study in a sample of Italian cancer genetics clinics

Abstract Purpose To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA genetic testing. Patients and methods The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008. Results 179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance [PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%)]. Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers. Conclusion Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment

Bright nanoparticles for an even brighter future: efficient production of luminescent carbon nanodots from olive mill wastewater

Este trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2016 do Instituto Politécnico de Lisboa. Código de referência IPL/2016/NANOLIVE/ISELCarbon nanodots (CNDs) are a very recent class of spherical-shaped nanosized carbon materials possessing average typical diameters < 10 nm. Since the very first reports on carbon dots,1,2 a variety of methods (top-down and bottom-up strategies), carbon sources and passivating agents, have dealt with their synthesis.3 The bottom-up approach, encompassing the use of pyrolytic/solvothermal processes, is more amenable for large-scale production and can cope with a large diversity of carbon precursors, either from natural or synthetic sources, typically endowed with acid, alcohol and amine functionalities.4 Some of the interesting CNDs properties include tunable photoluminescence, outstanding photostability and negligible cytotoxicity. These unique properties have prompted their intense and widespread use in several fields, such as fluorescent bioimaging and nanomedicine, chemo/biosensing, photocatalysis and optoelectronics.4info:eu-repo/semantics/publishedVersio