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Background and Purpose: ATP is highly accumulated in secretory vesicles and secreted upon exocytosis from neurons and endocrine cells. In adrenal chromaffin granules, intraluminal ATP reaches concentrations over 100 mM. However, how these large amounts of ATP contribute to exocytosis has not been investigated. Experimental Approach: Exocytotic events in bovine and mouse adrenal chromaffin cells were measured with single cell amperometry. Cytosolic Ca2+ measurements were carried out in Fluo‐4 loaded cells. Submembrane Ca2+ was examined in PC12 cells transfected with a membrane‐tethered Ca2+ indicator Lck‐GCaMP3. ATP release was measured using the luciferin/luciferase assay. Knockdown of P2X7 receptors was induced with short interfering RNA (siRNA). Direct Ca2+ influx through this receptor was measured using a P2X7 receptor‐GCamp6 construct. Key Results: ATP induced exocytosis in chromaffin cells, whereas the ectonucleotidase apyrase reduced the release events induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP), high KCl, or ionomycin. The purinergic agonist BzATP also promoted a secretory response that was dependent on extracellular Ca2+. A740003, a P2X7 receptor antagonist, abolished secretory responses of these secretagogues. Exocytosis was also diminished in chromaffin cells when P2X7 receptors were silenced using siRNAs and in cells of P2X7 receptor knockout mice. In PC12 cells, DMPP induced ATP release, triggering Ca2+ influx through P2X7 receptors. Furthermore, BzATP, DMPP, and KCl allowed the formation of submembrane Ca2+ microdomains inhibited by A740003. Conclusion and Implications: Autocrine activation of P2X7 receptors constitutes a crucial feedback system that amplifies the secretion of catecholamines in chromaffin cells by favouring submembrane Ca2+ microdomains. [ABSTRACT FROM AUTHOR]

The climate emergency has prompted rapid and intensive research into sustainable, reliable, and affordable energy alternatives. Offshore wind has developed and exceeded all expectations over the last 2 decades and is now a central pillar of the UK and other international strategies to decarbonise energy systems. As the dependence on variable renewable energy resources increases, so does the importance of the necessity to develop energy storage and nonelectric energy vectors to ensure a resilient whole-energy system, also enabling difficult-to-decarbonise applications, e.g. heavy industry, heat, and certain areas of transport. Offshore wind and marine renewables have enormous potential that can never be completely utilised by the electricity system, and so green hydrogen has become a topic of increasing interest. Although numerous offshore and marine technologies are possible, the most appropriate combinations of power generation, materials and supporting structures, electrolysers, and support infrastructure and equipment depend on a wide range of factors, including the potential to maximise the use of local resources. This paper presents a critical review of contemporary offshore engineering tools and methodologies developed over many years for upstream oil and gas (O&G), maritime, and more recently offshore wind and renewable energy applications and examines how these along with recent developments in modelling and digitalisation might provide a platform to optimise green hydrogen offshore infrastructure. The key drivers and characteristics of future offshore green hydrogen systems are considered, and a SWOT (strength, weakness, opportunity, and threat) analysis is provided to aid the discussion of the challenges and opportunities for the offshore green hydrogen production sector. [ABSTRACT FROM AUTHOR]

Problem During the 1980s, Spain had very strict laws limiting access to opioid agonist maintenance treatment (OAMT). Because of this, mortality among people who used illicit opioids and other illicit drugs was high. Spain was also the European country with the highest number of cases of acquired immunodeficiency syndrome transmitted through illicit drug injection. Approach The rapid spread of human immunodeficiency virus (HIV) infection among people using heroin led to a shift from a drug-free approach to the treatment of opioid dependence to one focused on harm reduction. A substantial change in legislation made it possible to meet public health needs and offer OAMT as part of harm reduction programmes in the public health system, including prisons. Local setting Legislative changes were made throughout the country, although at a different pace in different regions. Relevant changes Legal changes facilitated the expansion of OAMT, which has achieved a coverage of 60%. A parallel reduction in the annual incidence of HIV infection has been reported. Reductions in morbidity and mortality and improved health-related quality of life have been described in patients undergoing OAMT. Lessons learnt The treatment of opioid dependence has been more heavily influenced by moral concepts and prejudices that hinder legislation and interfere with the implementation of OAMT than by scientific evidence. To fulfil public health needs, OAMT should be integrated in harm reduction programmes offered primarily in public facilities, including prisons. Longitudinal studies are needed to detect unmet needs and evaluate programme impact and suitability. Probleme Dans les annees 1980, l'Espagne avait des lois tres strictes limitant l'acces au traitement de maintien par agoniste des opioides (TMAO). Pour cette raison, la mortalite parmi les utilisateurs d'opioides illicites et autres drogues illegales etait elevee. L'Espagne etait egalement le pays europeen presentant le plus grand nombre de cas de syndrome d'immunodeficience acquise transmis par injection de drogues illicites. Approche La propagation rapide du virus de l'immunodeficience humaine (VIH) chez les personnes consommant de l'heroine a mene au basculement d'une approche non medicalisee du traitement de la dependance aux opiaces a une position axee sur la reduction des risques. Un changement important de la legislation a permis de repondre aux besoins de sante publique et d'offrir un traitement de maintien par agoniste des opioides dans le cadre des programmes de reduction des risques dans les organismes de sante publique, y compris les prisons. Environnement local Des modifications legislatives ont ete apportees dans tout le pays, bien qu'a un rythme different selon les regions. Changements significatifs Les adaptations juridiques ont facilite le developpement du traitement de maintien par agoniste des opioides, qui a atteint une couverture de 60%. Une reduction parallele de l'incidence annuelle de l'infection par le VIH a ete observee. Des reductions de morbidite et de mortalite ainsi qu'une amelioration de la qualite de vie liee a la sante ont ete decrites chez les patients suivant un tel programme. Lecons tirees Le traitement de la dependance aux opiaces a ete plus fortement influence par des concepts moraux et les prejudices qui entravent la legislation et interferent avec la mise en place de programmes de traitement que par des preuves scientifiques. Afin de repondre aux besoins de sante publique, des traitements de maintien par agoniste des opioides devraient etre integres dans les programmes de reduction des risques, majoritairement proposes dans les lieux publics, y compris les prisons. Des etudes longitudinales sont necessaires pour detecter les besoins non satisfaits et pour evaluer l'impact et la pertinence du programme. Situacion Durante la decada de los anos 80, las estrictas leyes en Espana limitaban en acceso al tratamiento de mantenimiento con opioides agonistas, por lo que la mortalidad entre los consumidores de opiaceos y otras drogas ilegales era elevada. Espana era el pais europeo con el mayor numero de casos de sindrome de la inmunodeficiencia adquirida transmitidos por la inyeccion de drogas ilegales. Enfoque La rapida propagacion de la infeccion por el virus de la inmunodeficiencia humana (VIH) entre personas que consumian heroina ocasiono un cambio de un enfoque sin farmacos para el tratamiento de la dependencia de opiaceos a otro dirigido a la reduccion de danos. Un cambio importante en la legislacion permitio satisfacer las necesidades de salud publica y ofrecer el tratamiento de mantenimiento con opioides agonistas como parte de los programas de reduccion de danos en el sistema de salud publica, incluidas las prisiones. Marco regional Se realizaron cambios legislativos en todo el pais, aunque a un ritmo distinto en las diferentes regiones. Cambios importantes Los cambios legales facilitaron la expansion del tratamiento de mantenimiento con opioides agonistas, que alcanzo una cobertura del 60 %. Se ha constatado una reduccion paralela de la incidencia de la infeccion por el VIH, y se ha evidenciado una disminucion de la morbilidad y la mortalidad, asi como una mejora en la calidad de vida entre los pacientes que se someten al tratamiento de mantenimiento con opioides agonistas. Lecciones aprendidas El tratamiento de la dependencia de opiaceos ha estado mas influido por conceptos y prejuicios morales que dificultan la legislacion e interfieren en la puesta en marcha del tratamiento de mantenimiento con opioides agonistas que por las pruebas cientificas. A fin de cumplir con las necesidades de salud publica, se deberia integrar el tratamiento de mantenimiento con opioides agonistas en los programas de reduccion de danos ofrecidos en centros publicos, incluidas las prisiones. Es necesario realizar estudios longitudinales para detectar las necesidades insatisfechas y evaluar el impacto e idoneidad del programa., Introduction The epidemic of dependence on illicit drugs, especially heroin, began in Spain in the late 1970s. By 1980, the incidence of heroin use had peaked. (1) In addition, the [...]

Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, [alpha]-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult. Key Words: Liver--Inflammation--injury--Acute phase response--Aging.