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Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction

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World Journal of Cardiology 2020年第5期12卷 192-202页

作者： Natalie Cora Jennifer Ghandour Celina marie Pollard Victoria Lynn Desimine Krysten Elaine Ferraino janelle marie pereyra Rachel Valiente Anastasios Lymperopoulos Laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences(Pharmacology)College of PharmacyNova Southeastern UniversityFort LauderdaleFL 33328-2018United States

BACKGROUND Tobacco-related products,containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens,have been clearly associated with coronary artery disease,heart failure,stroke,and other heart *** the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system(RAAS)***,and its major metabolite in humans cotinine,have been reported to induce RAAS activation,resulting in aldosterone elevation in *** has various direct and indirect adverse cardiac *** is produced by the adrenal cortex in response to angiotensin II(AngII)activating AngII type 1 *** activity increases in chronic smokers,causing raised aldosterone levels(nicotine exposure causes the same in rats).AngII receptors exert their cellular effects via either G proteins or the twoβarrestins(βarrestin1 and-2).AIM Since adrenal?arrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans,we hypothesized that nicotine activates adrenal?arrestin1,which contributes to RAAS activation and heart disease *** We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulateβarrestin1 mRNA and protein levels,thereby enhancing AngII-dependent aldosterone synthesis and *** In contrast,siRNA-mediatedβarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295 R ***,nicotine promotes hyperaldosteronism via adrenalβarrestin1,thereby precipitating cardiac dysfunction,also in vivo,since nicotine-exposed experimental rats with adrenal-specificβarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenalβarrestin1 *** Adrenalβarrestin1 upregulation is one of the mechanisms by whic

关键词： Adrenocortical zona glomerulosa cell Aldosterone βarrestin Nicotine Signal transduction Tobacco-related heart disease

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Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection

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Journal of Intensive Medicine 2024年第1期4卷 81-93页

作者： marie Dejonckheere Massimo Antonelli Kostoula Arvaniti Koen Blot Ben CreaghBrown Dylan Wde Lange Jan De Waele Mieke Deschepper Yalim Dikmen George Dimopoulos Christian Eckmann Guy Francois Massimo Girardis Despoina Koulenti Sonia Labeau Jeffrey Lipman Fernando Lipovestky Emilio Maseda Philippe Montravers Adam Mikstacki JoseArtur Paiva Cecilia pereyra Jordi Rello JeanFrancois Timsit Dirk Vogelaers Stijn Blot the Abdominal Sepsis Study(AbSeS)group on behalf of the Trials Group of the European Society of Intensive Care Medicine Department of Internal Medicine and Pediatrics Faculty of Medicine and Health SciencesGhent UniversityGhentBelgium Department of Anesthesiology Intensive Care and Emergency MedicineFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly UniversitàCattolica del Sacro Cuore RomeItaly Intensive Care Unit Papageorgiou University Affiliated HospitalThessaloníkiGreece Department of Epidemiology and Public Health SciensanoIxellesBelgium Surrey Perioperative Anaesthetic Critical Care Collaborative Research Group(SPACeR) Royal Surrey County HospitalGuildfordUK Department of Clinical and Experimental Medicine University of SurreyGuildfordUK Department of Intensive Care Medicine University Medical Center UtrechtUniversity UtrechtUtrechtthe Netherlands Department of Intensive Care Medicine Ghent University HospitalGhentBelgium Data Science Institute Ghent University HospitalGhentBelgium Department of Anesthesiology and Reanimation Cerrahpasa School of MedicineIstanbul University-CerrahpasaIstanbulTurkey rd Department of Critical Care “EVGENIDIO”HospitalNational and Kapodistrian University of AthensAthensGreece Department of General Visceral and Thoracic SurgeryKlinikum Hannoversch-MuendenGoettingen UniversityGöttingenGermany Division of Scientific Affairs-Research European Society of Intensive Care MedicineBrusselsBelgium Anesthesia and Intensive Care Department University Hospital of ModenaModenaItaly UQ Centre for Clinical Research Faculty of MedicineThe University of QueenslandBrisbaneQLDAustralia nd Critical Care Department Attikon University HospitalAthensGreece Department of Nursing Faculty of EducationHealth and Social WorkUniversity College GhentGhentBelgium Jamieson Trauma Institute The University of QueenslandBrisbaneQLDAustralia Nimes University Hospital University of MontpellierNimesFrance Critical Care Department Hospital of the Interamerican Open University(UAI)Buenos AiresArgentina Surgical Critical Care Department of AnesthesiaHospital Universitario

Background:The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the(1)setting of infection onset(community-acquired,early onset,or late-onset hospital-acquired),(2)presence or absence of either localized or diffuse peritonitis,and(3)severity of disease expression(infection,sepsis,or septic shock).This classification system demonstrated reliable risk stratification in intensive care unit(ICU)patients with intra-abdominal *** study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and ***:This was a secondary analysis of an international observational study(“AbSeS”)investigating ICU patients with intra-abdominal *** patients with pancreatic infection were included in this analysis(n=165).Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the *** with mortality were assessed using logistic regression analysis and reported as odds ratio(OR)and 95%confidence interval(CI).Results:The overall mortality was 35.2%(n=58).The independent risk factors for mortality included older age(OR=1.03,95%CI:1.0 to 1.1 P=0.023),localized peritonitis(OR=4.4,95%CI:1.4 to 13.9 P=0.011),and persistent signs of inflammation at day 7(OR=9.5,95%CI:3.8 to 23.9,P<0.001)or after the implementation of additional source control interventions within the first week(OR=4.0,95%CI:1.3 to 12.2,P=0.013).Gramnegative bacteria were most frequently isolated(n=58,49.2%)without clinically relevant differences in microbial etiology between survivors and ***:In pancreatic infection,a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term *** this limited series,essentials of the AbSeS-classification,such as the setting of infection onset,diffuse

关键词： Pancreatic infection Intensive care unit Mortality Intra-abdominal infection Sepsis

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High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging

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Light(Science & Applications) 2018年第1期7卷 193-200页

作者： Sergey Turtaev Ivo T.Leite Tristan Altwegg-Boussac janelle M.P.Pakan Nathalie L.Rochefort Tomáš Čižmár Leibniz Institute of Photonic Technology Albert-Einstein-Straße 9Jena 07745Germany School of Life Sciences University of DundeeNethergateDundee DD14HNUK School of Science and Engineering University of DundeeNethergateDundee DD14HNUK Centre for Discovery Brain Sciences University of EdinburghHugh Robson Building 15George SquareEdinburgh EH89XDUK Center for Behavioral Brain Sciences Institute of Cognitive Neurology and Dementia ResearchGerman Center for Neurodegenerative DiseasesLeipziger Straße 44Haus 64Magdeburg 39120Germany Simons Initiative for the Developing Brain University of EdinburghEdinburgh EH89XDUK Institute of Scientific Instruments of CAS Kralovopolska 147Brno 61264Czech Republic

Progress in neuroscience relies on new techniques for investigating the complex dynamics of neuronal *** ongoing challenge is to achieve minimally invasive and high-resolution observations of neuronal activity in vivo inside deep brain *** introduced methods for holographic control of light propagation in complex media enable the use of a hair-thin multimode optical fibre as an ultranarrow imaging *** to endoscopes based on graded-index lenses or fibre bundles,this new approach offers a footprint reduction exceeding an order of magnitude,combined with a significant enhancement in *** designed a compact and high-speed system for fluorescent imaging at the tip of a fibre,achieving a resolution of 1.18±0.04μm across a 50-μm field of view,yielding 7-kilopixel images at a rate of 3.5 frames/***,we demonstrate in vivo observations of cell bodies and processes of inhibitory neurons within deep layers of the visual cortex and hippocampus of anaesthetised *** study paves the way for modern microscopy to be applied deep inside tissues of living animal models while exerting a minimal impact on their structural and functional properties.

关键词： multimode fibre vivo

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