Identification of 5,6-trans-epoxyeicosatrienoic acid in the phospholipids of red blood cells.

A novel eicosanoid, 5,6-trans-epoxy-8Z,11Z,14Z-eicosatrienoic acid (5,6-trans-EET), was identified in rat red blood cells. Characterization of 5,6-trans-EET in the sn-2 position of the phospholipids was accomplished by hydrolysis with phospholipase A(2) followed by gas chromatography/mass spectrometry as well as electrospray ionization-tandem mass spectrometry analyses. The electron ionization spectrum of 5,6-erythro-dihydroxyeicosatrienoic acid (5,6-erythro-DHET), converted from 5,6-trans-EET in the samples, matches that of the authentic standard. Hydrogenation of the extracted 5,6-erythro-DHET with platinum(IV) oxide/hydrogen resulted in an increase of the molecular mass by 6 daltons and the same retention time shift as an authentic standard in gas chromatography, suggesting the existence of three olefins as well as the 5,6-erythro-dihydroxyl structure in the metabolite. Match of retention times by chromatography indicated identity of the stereochemistry of the red blood cell 5,6-erythro-DHET vis à vis the synthetic standard. High pressure liquid chromatography-electrospray ionization-tandem mass spectrometry analysis of the phospholipase A(2)-hydrolyzed lipid extracts from red blood cells revealed match of the mass spectrum and retention time of the compound with the authentic 5,6-trans-EET standard, providing direct evidence of the existence of 5,6-trans-EET in red blood cells. The presence of other trans-EETs was also demonstrated. The ability of both 5,6-trans-EET and its product 5,6-erythro-DHET to relax preconstricted renal interlobar arteries was significantly greater than that of 5,6-cis-EET. In contrast, 5,6-cis-EET and 5,6-trans-EET were equipotent in their capacity to inhibit collagen-induced rat platelet aggregation, whereas 5,6-erythro-DHET was without effect. We propose that the red blood cells serve as a reservoir for epoxides which on release may act in a vasoregulatory capacity

Title Page Fenofibrate treatment of diabetic rats reduces nitrosative stress, renal COX-2 expression and enhanced renal prostaglandin release. JPET #129197 2 Running Title Page Running title: Fenofibrate and renal COX-2 in diabetes. Abbreviations AA -arac

Abstract Renal COX-2 expression is increased in the diabetic rat and has been linked to increased GFR and renal injury. Our studies indicate that oxidative stress in the form of peroxynitrite (ONOO) may be the stimulus for induction of COX-2. In this study, we addressed the effects of a PPARα agonist on renal COX-2 expression as fibrates exert renal protective effects. 48h after the induction of diabetes with streptozotocin in male Wistar rats, fenofibrate treatment (100mg/kg/day) was started and the effects compared to untreated diabetic rats and treated and untreated age-matched control rats (n=5 per group). After 12-14 weeks of treatment, the right kidney was perfused to determine prostaglandin release in response to arachidonic acid (AA) and the left kidney used to examine the expression of COX-2 and nitrotyrosine, an index of ONOO formation. Release of PGE 2 in response to AA was enhanced in the diabetic rat kidney compared to control (4.8±0.7 vs 1.9±0.7ng/min) and reduced by fenofibrate to 0.6±0.2ng/min. A similar pattern was obtained for AA-stimulated release of 6-ketoPGF 1α . The effects of fenofibrate were associated with reduced renal expression of COX-2 and nitrotyrosine in diabetic rats. We used creatinine clearance as an index of GFR, which was increased in the diabetic rat, 3.09±0.4 vs 1.15±0.1ml/min for control, and reduced by fenofibrate treatment to 1.87±0.3ml/min. These results show that fenofibrate treatment of diabetic rats decreases renal COX-2 expression, possibly by reducing nitrosative stress, and is associated with a reduction of the enhanced GFR

William Hodges 1744-1797: The Art of Exploration

William Hodges is well known as the artist accompanying Cook's second voyage to the South Pacific as official landscape painter. This book forms a major reappraisal of his career and reputation, arguing a central place for him in the development of British art. The eight essays that accompany this catalogue are by some of the foremost scholars in this area. They consider Hodges' work comparatively in terms of the rise of ethnology, the investigation of Indian history, the encounter with peoples 'without history' and the development of empirical science and rationalism. Previous accounts of Hodges have often treated him secondarily to Cook and the history of geographical exploration. This volume redresses this situation in the light of recent developments in the history of eighteenth-century British art, which seek to understand art and aesthetics within a broader frame of social and imperial history. In this work, Hodges is repositioned as one of the most intriguing and controversial painters of his age

Conflicting Visions: War and Visual Culture in Britain and France c. 1700-1830

Conflicting Visions: War and Visual Culture in Britain and France, c.1700-1830 offers the first systematic reappraisal of the visual representation of war in Britain and France during the 'long' eighteenth century. This radical collection of essays explores the relation of visual imagery and aesthetics to conflict during this important period, drawing upon a wealth of materials including paintings and prints, maps and topographical drawings, commemorative sculpture and historical artefacts. The intriguing case studies reveal that military conflict was not a sphere of social activity separated from artistic culture but rather a determining factor in cultural production, and that war itself was comprehended, debated and experienced through those products. Key themes and preoccupations - how differing ideas of the public were predicated by the representation of war; how such notions were shaped by the imperial contexts of war; the relations between conflict, national identity and historical memory - are addressed to show that war served as a primary vehicle for the representation of numerous associated and contested issues, including patriotism and the idea of the nation, loyalty and opposition, heroism and masculinity, sympathy and sensibility

Introduction

Conficting Visions examines the cultural representation of war, conquest and the military in Britian and France during the 'long' eighteenth century. More specifically this book explores the relation of visual culture and aesthetics to conflict in the period, taking into account a wide variety of materials, including paintings and prints, maps and topographical drawings, commemorative sculpture and historical artefacts. These range from art of the most deliberately high-minded character to illustrative imagery of more modest aesthetic intent, from the direct illustration of individual conflicts to the allegorical and allusive representation of warfare and military endeavour. Together the chapters show conflict to be a determining factor in cultural production and war itself as largely comprehended, debated and experienced through those products. While this is not to deny the actual material effects of warfare upon ordinary people, most directly in terms of enlistment of family or friends, or indirectly through economic hardship or benefit, it might be argued that for the majority conflict was primarily envisaged, encountered and mediated through a variety of cultural forms