Angiotensin II Induces Neutrophil Accumulation In Vivo Through Generation and Release of CXC Chemokines

Background— Angiotensin II (Ang II) is implicated in the development of cardiac ischemic disorders in which prominent neutrophil accumulation occurs. Ang II can be generated intravascularly by the renin-angiotensin system or extravascularly by mast cell chymase. In this study, we characterized the ability of Ang II to induce neutrophil accumulation. Methods and Results— Intraperitoneal administration of Ang II (1 nmol/L) induced significant neutrophil recruitment within 4 hours (13.3±2.3x106 neutrophils per rat versus 0.7±0.5x106 in control animals), which disappeared by 24 hours. Maximal levels of CXC chemokines were detected 1 hour after Ang II injection (577±224 pmol/L cytokine-inducible neutrophil chemoattractant [CINC]/keratinocyte-derived chemokine [KC] versus 5±3, and 281±120 pmol/L macrophage inflammatory protein [MIP-2] versus 14±6). Intravital microscopy within the rat mesenteric microcirculation showed that the short-term (30 to 60 minutes) leukocyte–endothelial cell interactions induced by Ang II were attenuated by an anti-rat CINC/KC antibody and nearly abolished by the CXCR2 antagonist SB-517785-M. In human umbilical vein endothelial cells (HUVECs) or human pulmonary artery media in culture, Ang II induced interleukin (IL)-8 mRNA expression at 1, 4, and 24 hours and the release of IL-8 at 4 hours through interaction with Ang II type 1 receptors. When HUVECs were pretreated with IL-1 for 24 hours to promote IL-8 storage in Weibel-Palade bodies, the Ang II–induced IL-8 release was more rapid and of greater magnitude. Conclusions— Ang II provokes rapid neutrophil recruitment, mediated through the release of CXC chemokines such as CINC/KC and MIP-2 in rats and IL-8 in humans, and may contribute to the infiltration of neutrophils observed in acute myocardial infarction.Mata Roig, Manuel, [email protected] ; Cortijo Gimeno, Julio, [email protected] ; Morcillo Sanchez, Esteban Jesus, [email protected] ; Jose, Peter J., [email protected] ; Sanz Ferrando, Maria Jesus, [email protected]

Non-Destructive Techniques Based on Eddy Current Testing

Non-destructive techniques are used widely in the metal industry in order to control the quality of materials. Eddy current testing is one of the most extensively used non-destructive techniques for inspecting electrically conductive materials at very high speeds that does not require any contact between the test piece and the sensor. This paper includes an overview of the fundamentals and main variables of eddy current testing. It also describes the state-of-the-art sensors and modern techniques such as multi-frequency and pulsed systems. Recent advances in complex models towards solving crack-sensor interaction, developments in instrumentation due to advances in electronic devices, and the evolution of data processing suggest that eddy current testing systems will be increasingly used in the future

Disruption of the CCL1-CCR8 axis inhibits vascular Treg recruitment and function and promotes atherosclerosis in mice

The CC chemokine 1 (CCL1, also called I-309 or TCA3) is a potent chemoattractant for leukocytes that plays an important role in inflammatory processes and diseases through binding to its receptor CCR8. Here, we investigated the role of the CCL1-CCR8 axis in atherosclerosis. We found increased expression of CCL1 in the aortas of atherosclerosis-prone fat-fed apolipoprotein E (Apoe)-null mice; moreover, in vitro flow chamber assays and in vivo intravital microscopy demonstrated an essential role for CCL1 in leukocyte recruitment. Mice doubly deficient for CCL1 and Apoe exhibited enhanced atherosclerosis in aorta, which was associated with reduced plasma levels of the anti-inflammatory interleukin 10, an increased splenocyte Th1/Th2 ratio, and a reduced regulatory T cell (Treg) content in aorta and spleen. Reduced Treg recruitment and aggravated atherosclerosis were also detected in the aortas of fat-fed low-density lipoprotein receptor-null mice treated with CCR8 blocking antibodies. These findings demonstrate that disruption of the CCL1-CCR8 axis promotes atherosclerosis by inhibiting interleukin 10 production and Treg recruitment and function.This study was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU, grants SAF2016-79490-R and SAF2014-57845-R) and the Instituto de Salud Carlos III (ISCIII, grants PI14/00526, PI17/01395, CP11/00145, and CPII16/00022) with co-funding from the European Regional Development Fund (ERDF, “Una manera de hacer Europa”), the Fundación Ramón Areces, European Union (EuroCellNet COST Action CA15214) and the INSERM. VZG is supported by the ISCIII, JMG-G by the ISCIII Miguel Servet Program and the Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), AdMM by the MCIU (predoctoral contract BES-2014-06779), and ZM by a British Heart Foundation Professorship. The CNIC is supported by the MCIU and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Local Oxidative and Nitrosative Stress Increases in the Microcirculation during Leukocytes-Endothelial Cell Interactions

Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O2•−) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O2•− and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O2•− and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O2•− and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ∼0.6 fold, O2•− increased ∼27 fold and peroxynitrite increased ∼30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase in O2•− and peroxynitrite concentration in the lumen. The increased O2•− and peroxynitrite can cause leukocytes priming through peroxynitrite and leukocytes activation through secondary stimuli of O2•− in bloodstream without endothelial interaction. This finding supports that leukocyte rolling/adhesion and activation are independent events

Constructive Research Study of Location-Proximity Privacy-Preserving Algorithm Capabilities as Part of a Mobile Application

Location Based Services (LBS) have been responsible for several privacy breaches of their users in recent years and a number of researchers have put forward solutions towards making LBS more secure in regards to user location privacy. However, the proposed protocols were rarely tested in real conditions. This research study will create an artifact, an Android application that implements one of the state-of-the-art protocols for location privacy preservation, and test its performance to determine if the state of the protocols is at a stage where it can be implemented in real world applications. We have found that the performance of our artifact in short distances is comparable to real applications as it took 5 seconds to check proximity between users in 25 meter radius. However, the computation time increases drastically with increase in radius values and the protocol took 72 seconds to check proximity for 100 meter radius. Such time frames are insufficient as we believe most users are not willing to wait so long for an application to process their requests. Therefore we were unable to show that the state-of-the-art location privacy-preserving algorithms are ready for adaptation in real world applications, although certain modifications to coordinate precision could correct that

Attitudes of Saudi Arabian secondary school pupils towards the learning of English

SIGLEAvailable from British Library Document Supply Centre-DSC:DX192808 / BLDSC - British Library Document Supply CentreGBUnited Kingdo