The ‘EDHF’ Antagonist 14, 15 Epoxyeicosa-5(Z)-Enoic Acid has Vasodilator Properties in Mesenteric Vessels

There is now overwhelming evidence for Epoxyeicosatrienoic acids (EETs) as endothelial derived hyperpolarising factor (EDHF). Most recently, a number of pharmacological tools have been developed for the study of EETs in relation to EDHF responses. EETs have been shown to cause relaxation by activating smooth muscle large conductance Ca2+ sensitive K+ (BKCa) (Archer et al, 2003). This dilatory response has been shown to be specifically inhibited by its analogue 14, 15-epoxyeicosa-5 (Z) enoic acid (14, 15 EEZE) in both human internal mammary artery and bovine coronary artery (Archer et al, 2003). Here we have investigated the antagonist effects of 14, 15 EEZE in murine arteries. Male Black 6 mice (12-18 weeks) were killed by lethal exposure to CO2. First order arteries were isolated and mounted in wire myographs immersed in physiological salt solution (PSS). Arteries were equilibrated (30 mins) and tensions normalised as described previously (Mulvany and Halpern, 1977). Arteries incubated for 30 minutes with or without 3µg/ml 14, 15 EEZE. A concentration response curve to 11, 12 EET was performed cumulatively on arteries pre-contracted with EC80 U46619. In some experiments, arteries were pre-contracted with EC80 U46619, and concentration response to 14, 15 EEZE performed cumulatively.Non peer reviewe

Nitric oxide-dependent vasodilation is compromised in isolated pulmonary arteries from COX knockout mice

Cyclooxygenase (COX) has two isoforms and is essential for prostanoid synthesis. COX-1 is constitutive whilst COX-2 is induced in inflammation. Two COX products, prostacyclin (PGI2) and thromboxane (TxA2), regulate vessel tone; PGI2 mediates vasodilation and platelet inhibition, and TxA2 opposes this. PGI2 therapies are used in pulmonary arterial hypertension (PAH). Endogenous TxA2/PGI2 has been linked to PAH in animal models, but the mechanism and isoform involved is debated. We hypothesized that pulmonary artery (PA) from COX-1–/– and COX-2–/– mice would have altered vasodilatory function compared with wild-type (WT; C57Bl6) mice. Vasomotor responses to contractile and relaxant agents were measured by myography. PA from all mice responded similarly to contraction by high potassium or the TxA2 mimetic, U46619. Relaxation to PGI2 receptor or PPARβ/ agonists was also similar in all PAs. However, COX-1–/– and, to a lesser extent, COX-2–/– PA had impaired vasodilation to acetylcholine (ACh), which stimulates endothelial nitric oxide (NO) release, and COX-1–/– PA also dilated less to sodium nitroprusside (SNP); an NO donor that works on smooth muscle (Fig 1). These data indicate an interaction between COX and NO sensing pathways in pulmonary vessels, and have implications for our understanding of PAH.Non peer reviewedFinal Accepted Versio

Eicosanoid turnover in GtoPdb v.2021.3

Eicosanoids are 20-carbon fatty acids, where the usual focus is the polyunsaturated analogue arachidonic acid and its metabolites. Arachidonic acid is thought primarily to derive from phospholipase A2 action on membrane phosphatidylcholine, and may be re-cycled to form phospholipid through conjugation with coenzyme A and subsequently glycerol derivatives. Oxidative metabolism of arachidonic acid is conducted through three major enzymatic routes: cyclooxygenases; lipoxygenases and cytochrome P450-like epoxygenases, particularly CYP2J2. Isoprostanes are structural analogues of the prostanoids (hence the nomenclature D-, E-, F-isoprostanes and isothromboxanes), which are produced in the presence of elevated free radicals in a non-enzymatic manner, leading to suggestions for their use as biomarkers of oxidative stress. Molecular targets for their action have yet to be defined

Eicosanoid turnover in GtoPdb v.2023.1

Eicosanoids are 20-carbon fatty acids, where the usual focus is the polyunsaturated analogue arachidonic acid and its metabolites. Arachidonic acid is thought primarily to derive from phospholipase A2 action on membrane phosphatidylcholine, and may be re-cycled to form phospholipid through conjugation with coenzyme A and subsequently glycerol derivatives. Oxidative metabolism of arachidonic acid is conducted through three major enzymatic routes: cyclooxygenases; lipoxygenases and cytochrome P450-like epoxygenases, particularly CYP2J2. Isoprostanes are structural analogues of the prostanoids (hence the nomenclature D-, E-, F-isoprostanes and isothromboxanes), which are produced in the presence of elevated free radicals in a non-enzymatic manner, leading to suggestions for their use as biomarkers of oxidative stress. Molecular targets for their action have yet to be defined

Cyclooxygenase (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Prostaglandin (PG) G/H synthase, most commonly referred to as cyclooxygenase (COX, (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate,hydrogen-donor : oxygen oxidoreductase) activity, catalyses the formation of PGG2 from arachidonic acid. Hydroperoxidase activity inherent in the enzyme catalyses the formation of PGH2 from PGG2. COX-1 and -2 can be nonselectively inhibited by ibuprofen, ketoprofen, naproxen, indomethacin and paracetamol (acetaminophen). PGH2 may then be metabolised to prostaglandins and thromboxanes by various prostaglandin synthases in an apparently tissue-dependent manner

Eicosanoid turnover (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database

Eicosanoids are 20-carbon fatty acids, where the usual focus is the polyunsaturated analogue arachidonic acid and its metabolites. Arachidonic acid is thought primarily to derive from phospholipase A2 action on membrane phosphatidylcholine, and may be re-cycled to form phospholipid through conjugation with coenzyme A and subsequently glycerol derivatives. Oxidative metabolism of arachidonic acid is conducted through three major enzymatic routes: cyclooxygenases; lipoxygenases and cytochrome P450-like epoxygenases, particularly CYP2J2. Isoprostanes are structural analogues of the prostanoids (hence the nomenclature D-, E-, F-isoprostanes and isothromboxanes), which are produced in the presence of elevated free radicals in a non-enzymatic manner, leading to suggestions for their use as biomarkers of oxidative stress. Molecular targets for their action have yet to be defined

Cyclooxygenase in GtoPdb v.2023.1

Prostaglandin (PG) G/H synthase, most commonly referred to as cyclooxygenase (COX, (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate,hydrogen-donor : oxygen oxidoreductase) activity, catalyses the formation of PGG2 from arachidonic acid. Hydroperoxidase activity inherent in the enzyme catalyses the formation of PGH2 from PGG2. COX-1 and -2 can be nonselectively inhibited by ibuprofen, ketoprofen, naproxen, indomethacin and paracetamol (acetaminophen). PGH2 may then be metabolised to prostaglandins and thromboxanes by various prostaglandin synthases in an apparently tissue-dependent manner

Sites of Conversation

Through our lives we sit at many tables, eating, preparing food, playing, making drawings, doing homework, working and more. In other words, the table is a focal point where words and materials meet, cross each-other, collide or come together. The table can take us to a space and time where forgotten memories emerge and embodied actions are found. The Phenomenology and Imagination Research Group (PIRG) is an independent research group whose aim is to develop research through active fine art collective practice. PIRG’s Table Method (tm) is a process that has grown organically over a period of five years and has been cultivated through a desire to bring words, texts, actions and materials together as it invites participants to respond to a text through conversation, the handling of materials and tools.  The work draws from the new materialist turn through the ideas of Gaston Bachelard, Maurice Merleau-Ponty, Karen Barad and Jane Bennett.  PIRG has extended its practice of conversation as a research methodology to include the phenomenological and material interaction that has become the tm. The tm is an unfolding dialogue between materials and phenomenological thinking, which expands the possibilities of what conversation can be and become, it utilises material thinking as a way to open out discourse beyond the constraints of language and other representations

"I can't make all this work." : end of life care provision in natural disasters : a qualitative study

Background: Natural disasters are becoming more frequent and severe and profoundly impact the end-of-life care experience, including service provision. There is a paucity of research examining healthcare workers’ experiences in responding to care demands when disasters strike. This research aimed to fill this gap by exploring end-of-life care providers’ perceptions of the impact of natural disasters on end-of-life care. Methods: Between Feb 2021-June 2021 ten in-depth semi-structured interviews were conducted with healthcare professionals providing end-of-life care during recent natural disasters, COVID-19, and/or fires and floods. Interviews were audio-recorded, transcribed, and analysed using a hybrid inductive and deductive thematic approach. Results: The overarching theme from the healthcare workers’ accounts was of being unable to provide effective compassionate and quality care - “I can’t make all this work.” They spoke of the considerable burdens the system imposed on them, of being overextended and overwhelmed, having their roles overturned, and losing the human element of care for those at end-of-life. Conclusion: There is urgent need to pioneer effective solutions to minimise the distress of healthcare professionals in delivering end-of-life care in disaster contexts, and to improve the experience of those dying