Dysregulation of Prostaglandins, Leukotrienes and Lipoxin A4 in Bronchiectasis

Introduction: Bronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis. Aim: The aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state. Methods: Six healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF). Results: In the stable state, in serum there were significantly higher levels of prostaglandin E2 (PGE2), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B4 (LTB4) in patients with moderate–severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A4 (LXA4) in severe bronchiectasis. In BALF, there were significantly higher levels of PGE2, 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB4 in moderate–severe patients compared with healthy volunteers. In the stable state, there was a negative correlation of PGE2 and LTB4 with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses. LXA4 improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA4 reduced neutrophil activation and degranulation. Conclusion: There is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA4 improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA4 in bronchiectasis warrants further studies

Partners No More: Relational Transformation and the Turn to Litigation in Two Conservationist Organizations

The rise in litigation against administrative bodies by environmental and other political interest groups worldwide has been explained predominantly through the liberalization of standing doctrines. Under this explanation, termed here the floodgate model, restrictive standing rules have dammed the flow of suits that groups were otherwise ready and eager to pursue. I examine this hypothesis by analyzing processes of institutional transformation in two conservationist organizations: the Sierra Club in the United States and the Society for the Protection of Nature in Israel (SPNI). Rather than an eagerness to embrace newly available litigation opportunities, as the floodgate model would predict, the groups\u27 history reveals a gradual process of transformation marked by internal, largely intergenerational divisions between those who abhorred conflict with state institutions and those who saw such conflict as not only appropriate but necessary to the mission of the group. Furthermore, in contrast to the pluralist interactions that the floodgate model imagines, both groups\u27 relations with pertinent agencies in earlier eras better accorded with the partnership-based corporatist paradigm. Sociolegal research has long indicated the importance of relational distance to the transformation of interpersonal disputes. I argue that, at the group level as well, the presence or absence of a (national) partnership-centered relationship determines propensities to bring political issues to court. As such, well beyond change in groups\u27 legal capacity and resources, current increases in levels of political litigation suggest more fundamental transformations in the structure and meaning of relations between citizen groups and the state

Cities of the world : World regional urban development

Remarkably, more than half the world's population now lives in cities, and the number graw daily as people abandon rural areas

Lebanon Bologna, Cola Champagne, Macaroni & Cheese: Childhood Food Autobiography as Intergenerational, Geospatial, and Historical Communication

LIfespan Communication, Geography and Food (COMM/GEOG 695) is a new graduate course taught by THOMAS J. SOCHA (professor and director of the graduate program in lifespan and digital communication) and DONALD ZEIGLER (professor of geography). The course examines intersections of communication, geography and food from lifespan and global perspectives. Socha and Zeigler will present highlights from their course and students will read excerpts from their food autobiographies, relating to cultural and personal identities in childhood food memories, dinner table talk, folk culture and victual rituals. Socha has published six books and over 30 articles and chapters about family communication and was the founding editor of the Journal of Family Communication. Zeigler teaches courses in cultural and urban geography, the Middle East and Latin America, plus distance learning courses for teachers. His co-edited book on Cities of the World is going into its sixth edition

Cities of the World: Regional Patterns and Urban Environments

Remarkably, more than half of the world\u27s population now lives in cities, and the numbers grow daily as people abandon rural areas. This fully updated and revised seventh edition of the classic text offers readers a comprehensive set of tools for understanding the urban landscape, and, by extension, the world\u27s politics, cultures, and economies. Providing a sweeping overview of world urban geography, noted experts explore the eleven major global regions. Each regional chapter considers urban history, economy, culture, and environment, as well as urban spatial models and problems and prospects. Each begins with two facing pages: a regional map that shows the major cities and a table of basic statistical information about cities and urbanization in each region and a list of ten salient points about that region’s urban experience. Chapters conclude with a list of references, including films and webpages, which can be used by the student and instructor for additional information about specific cities. … [Amazon.com]https://digitalcommons.odu.edu/politicalscience_geography_books/1038/thumbnail.jp

Neuregulin-1 inhibits neuroinflammatory responses in a rat model of organophosphate-nerve agent-induced delayed neuronal injury.

BackgroundNeuregulin-1 (NRG-1) has been shown to act as a neuroprotectant in animal models of nerve agent intoxication and other acute brain injuries. We recently demonstrated that NRG-1 blocked delayed neuronal death in rats intoxicated with the organophosphate (OP) neurotoxin diisopropylflurophosphate (DFP). It has been proposed that inflammatory mediators are involved in the pathogenesis of OP neurotoxin-mediated brain damage.MethodsWe examined the influence of NRG-1 on inflammatory responses in the rat brain following DFP intoxication. Microglial activation was determined by immunohistchemistry using anti-CD11b and anti-ED1 antibodies. Gene expression profiling was performed with brain tissues using Affymetrix gene arrays and analyzed using the Ingenuity Pathway Analysis software. Cytokine mRNA levels following DFP and NRG-1 treatment was validated by real-time reverse transcription polymerase chain reaction (RT-PCR).ResultsDFP administration resulted in microglial activation in multiple brain regions, and this response was suppressed by treatment with NRG-1. Using microarray gene expression profiling, we observed that DFP increased mRNA levels of approximately 1,300 genes in the hippocampus 24 h after administration. NRG-1 treatment suppressed by 50% or more a small fraction of DFP-induced genes, which were primarily associated with inflammatory responses. Real-time RT-PCR confirmed that the mRNAs for pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly increased following DFP exposure and that NRG-1 significantly attenuated this transcriptional response. In contrast, tumor necrosis factor α (TNFα) transcript levels were unchanged in both DFP and DFP + NRG-1 treated brains relative to controls.ConclusionNeuroprotection by NRG-1 against OP neurotoxicity is associated with the suppression of pro-inflammatory responses in brain microglia. These findings provide new insight regarding the molecular mechanisms involved in the neuroprotective role of NRG-1 in acute brain injuries