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Dexamethasone, tetrahydrobiopterin and uncoupling of endothelial nitric oxide synthase

Journal of Geriatric Cardiology 2015年第5期12卷 528-539页

作者： Silke Tobias Alice Habermeier Daniel Siuda Gisela Reifenberg Ning Xia Ellen I Closs ulrich forstermann Huige Li Department of Pharmacology Johannes Gutenberg University Medical Center Mainz Germany

Objective To find out whether dexamethasone induces an uncoupling of the endothelial nitric oxide synthase （eNOS）. Methods ＆ Results A major cause of eNOS uncoupling is a deficiency of its cofactor tetrahydrobiopterin （BH4）. Treatment of human *** 926 endothelial cells with dexamethasone decreased mRNA and protein expression of both BH4-synthesizing enzymes： GTP cyclobydrolase I and dihydrofolate reductase. Consistently, a concentration- and time-dependent reduction of BH4, dihydrobiopterin （BH2） as well as BH4：BH2 ratio was observed in dexamethasone-treated cells. Surprisingly, no evidence for eNOS uncoupling was found. We then analyzed the expression and phosphorylation of the eNOS enzyme. Dexamethasone treatment led to a down-regulation of eNOS protein and a reduction of eNOS phosphorylation at serine 1177. A reduction of eNOS expression may lead to a relatively normal BH4： eNOS molar ratio in dexamethasone-treated cells. Because the BH4-eNOS stoichiometry rather than the absolute BH4 amount is the key determinant of eNOS functionality （i.e., coupled or uncoupled）, the down-regulation of eNOS may represent an explanation for the absence of eNOS uncoupling. Phosphorylation of eNOS at serine 1177 is needed for both the NO-producing activity of the coupled eNOS and the superoxide-producing activity of the uncoupled eNOS. Thus, a reduction of serine 1177 phosphorylation may render a potentially uncoupled eNOS hardly detectable. Conclusions Although dexamethasone reduces BH4 levels in endothelial cells, eNOS uncoupling is not evident. The reduction of NO production in dexamethasone-treated endothelial cells is mainly attributable to reduced eNOS expression and decreased eNOS phosphorylation at serine 1177.

关键词： Dexamethasone Endothelial cells eNOS uncoupling Nitric oxide synthase Reactive oxygen species Tetrahydrobiopterin

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Contribution of uncoupled endothelial NO synthase （eNOS） to vascular disease

Contribution of uncoupled endothelial NO synthase （eNOS） t...

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第十五届国际药理学大会

作者： ulrich forstermann Department of Pharmacology Johannes Gutenberg University55101 MainzGermany

＜正＞ Nitric oxide （NO） produced by eNOS is an important protective molecule in the vasculature. A functional eNOS oxidizes L-arginine to L-citrulline and NO. This normal function of eNOS requires dimerization of the enzyme,the presence of the substrate L-arginine. and the essential cofactor （6R）-5, 6, 7, 8-tetrahydro-L-biopterin （BH4）. Cardiovascular risk factors stimulate the production of reactive oxygen species （ROS） in the vasculature. NADPH oxidases represent major sources of ROS and have been found upregulated and activated in cardiovascular disease. Superoxide avidly reacts with vascular NO to form peroxynitrite. The cofactor BH4 is highly sensitive to oxidation by peroxynitrite. Diminished levels of BH4 promote eNOS uncoupling （i.e. superoxide production by eNOS）. Uncoupling of eNOS has been observed in several in vitro models, in animal models of cardiovascular diseases, and in patients with cardiovascular risk factors. BH4 has been shown to correct eNOS dysfunction in animal models and patients. In addition, folic acid and infusions of vitamin C are able to restore eNOS functionality, most probably by enhancing BH4 levels as well.

关键词： endothelial NO synthase tetrahydro-L-biopterin oxidative stress peroxynitrite

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Janus-faced roles of endothelial NO synthase in vascular disease:Can pharmacology uphold the favorable side?

Janus-faced roles of endothelial NO synthase in vascular dis...

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11th International Vascular Neuroeffector Mechanisms and Cardiovascular Pharmacology and Medicine Symposia, Shanghai-Suzhou 2006

作者： ulrich forstermann Sven Horke Department of Pharmacology Johannes Gutenberg University 55101 Mainz Germany Department of Pharmacology Johannes Gutenberg University 55101 Mainz Germany

Endothelium-derived nitric oxide (NO) exerts important protective functions in the vasculature. These include prevention of platelet adhesion, reduced expression of chemokines and adhesion molecules and inhibition of smooth muscle proliferation. Endothelial NO synthase (eNOS) is the predominant enzyme responsible for vascular NO synthesis. A functional eNOS transfers

关键词： Janus-faced roles of endothelial NO synthase in vascular disease:Can pharmacology uphold the favorable side

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Empowerment in chronic wound care——exploring the scope for patient contribution

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Frontiers of Nursing 2024年第1期11卷 1-16页

作者： Benedikt Hackert Ewa Klara Stürmer ulrich Weger Department of Psychology and Psychotherapy University of Witten/HerdeckeAlfred-Herrhausen-Straße 5058448 WittenGermany Department for Vascular Medicine University Heart and Vascular Center HamburgUniversity Medical Center Hamburg-EppendorfMartinistreet 5220246 HamburgGermany

Objective:In this study,we investigated the concept of empowerment in chronic wound care and propose to facilitate patient control by making use of degrees of freedom(DOF):that is,shaping of everyday wound care tasks initiated by patients and based on their wishes,mostly in terms of patients executing treatment steps,requesting or directing health care professionals to under take changes,or modifications of internal ***:As a first step,we conducted a systematic literature search,followed by an inductive form of qualitative content analysis,which resulted in the identification of 5 dimensions as main elements of empowerment:education and shared decision making,adherence to self-care behaviors,responsibility and control,general call for empowerment,and ***,the latter are noticeably absent in the *** investigate patients'freedom in shaping the wound care process,we conducted a second literature ***:A number of possibilities for patients to influence the wound care process could be identified,but experimental or clinical evidence about their effects is missing,their variety is limited,and they are only inadequately ***:However,DOF should be an indispensable aspect of genuine empowerment,since they allow patients to occupy the role of the agent in the treatment process and give rise to the subjective experience of feeling ***,in the third part,we develop a research proposal on how to investigate and include DOF in the clinical practice of wound ***,limitations about implementations are discussed(e.g.,patients being reluctant to overcome their passive role,resulting in frustration for health care professionals).

关键词： adherence chronic wounds control degrees of freedom empowerment shared decision making

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Enzymatic C1 reduction using hydrogen in cofactor regeneration

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Frontiers of Chemical Science and Engineering 2024年第7期18卷 33-40页

作者： Ruishuang Sun Chenqi Cao Qingyun Wang Hui Cao ulrich Schwaneberg Yu Ji Luo Liu Haijun Xu Beijing Bioprocess Key Laboratory Beijing University of Chemical TechnologyBeijing 100029China Institute of Biotechnology Rheinisch-Westfälische Technische Hochschale(RWTH)AachenAachen 52074Germany

Carbon dioxide fixation presents a potential solution for mitigating the greenhouse gas *** carbon dioxide fixation,C1 compound reduction requires a high energy *** calculations suggest that the energy source for cofactor regeneration plays a vital role in the effective enzymatic C1 *** utilizes renewable hydrogen to achieve the regeneration and supply cofactor nicotinamide adenine dinucleotide(NADH),providing a driving force for the reduction reaction to reduce the thermodynamic barrier of the reaction cascade,and making the forward reduction pathway thermodynamically *** on the regeneration of cofactor NADH by hydrogenase,and coupled with formaldehyde dehydrogenase and formolase,a favorable thermodynamic mode of the C1 reduction pathway for reducing formate to dihydroxyacetone(DHA)was designed and *** resulted in accumulation of 373.19μmol·L^(-1) DHA after 2 h,and conversion reaching 7.47%.These results indicate that enzymatic utilization of hydrogen as the electron donor to regenerate NADH is of great significance to the sustainable and green development of bio-manufacturing because of its high economic efficiency,no by-products,and environment-friendly ***,formolase efficiently and selectively fixed the intermediate formaldehyde(FALD)to DHA,thermodynamically pulled formate to efficiently reduce to DHA,and finally stored the low-grade renewable energy into chemical energy with high energy density.

关键词： [NiFe]-hydrogenase SH formolase NADH regeneration C1 compound reduction thermodynamic calculation

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A simulation study on spatial and time resolution for a cost-effective positron emission particle tracking system

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Particuology 2024年第5期88卷 312-322页

作者： Josephine Oppotsch Matthias Steinke Miriam Fritsch Fritz-Herbert Heinsius Thomas Held Nikoline Hilse Viktor Scherer ulrich Wiedner Ruhr-Universität Bochum Institut für Experimentalphysik I44801 BochumGermany Ruhr-Universität Bochum Lehrstuhl für Energieanlagen und Energieprozesstechnik44801 BochumGermany

This work is the second part of a simulation study investigating the processing of densely packed and moving granular assemblies by positron emission particle tracking (PEPT).Since medical positron emission tomography (PET) scanners commonly used for PEPT are very expensive,a PET-like detector system based on cost-effective organic plastic scintillator bars is being developed and tested for its *** this context,the spatial resolution of a resting positron source,a source moving on a freely designed model path,and a particle motion given by a discrete element method (DEM) simulation is studied using Monte Carlo simulations and the software toolkit *** not only extended the simulation and reconstruction to a moving source but also significantly improved the spatial resolution compared to previous work by adding oversampling and iteration to the reconstruction ***,in the case of a source following a trajectory developed from DEM simulations,a very good resolution of about 1 mm in all three directions and an average 3D deviation between simulated and reconstructed events of 2.3 mm could be ***,the resolution for realistic particle motion within the generic grate system (which is the test rig for further experimental studies) is well below the smallest particle *** simulation of the dependence of the reconstruction accuracy on tracer particle location revealed a nearly constant efficiency within the entire detector system,which demonstrates that boundary effects can be neglected.

关键词： Positron emission particle tracking Monte Carlo method Time-of-flight Plastic scintillators Silicon photomultipliers(SiPMs)

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A simulation study for a cost-effective PET-like detector system intended to track particles in granular assemblies

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Particuology 2024年第1期84卷 117-125页

作者： Josephine Oppotsch Antonios Athanassiadis Miriam Fritsch Fritz-Herbert Heinsius Thomas Held Nikoline Hilse Viktor Scherer Matthias Steinke ulrich Wiedner Ruhr-Universität Bochum Institut für Experimentalphysik I44801 BochumGermany Ruhr-Universität Bochum Lehrstuhl für Energieanlagen und Energieprozesstechnik44801 BochumGermany

Since many industrial applications rely on the processing of densely packed and moving granular ma-terial,obtaining bulk internal information on the particle movement inside the reactors is of great *** information can be delivered by Positron Emission Particle Tracking(PEPT).By marking pellets with a positron-emitting radioisotope,the position of these tracer particles can be determined via the time-of-flight differences of the emitted gamma-ray *** current paper proposes a PET-like detector system based on cost-effective organic plastic scintillators instead of the more common but expensive inorganic *** system is currently under construction and was tested for its resolution and efficiency in this simulation *** Monte Carlo simulations and the software toolkit Geant4,three different geometries(an empty glass box,a generic grate system,and a cubic box of 1 m3 completely filled with pellets)were investigated,leading to a spatial resolution in the millimeter range and an efficiency,defined as the ratio of reconstructed decay locations to simulated decays,of 2.7%,1.4%,and 0.3%.

关键词： Positron emission particle tracking Geant4 Monte Carlo method Time-of-flight Plastic scintillators Silicon photomultipliers(SiPMs)

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Dynamic convergent shock compression initiated by return current in high-intensity laser-solid interactions

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Matter and Radiation at Extremes 2024年第4期9卷 40-53页

作者： Long Yang Martin Rehwald Thomas Kluge Alejandro LasoGarcia Toma Toncian Karl Zeil ulrich Schramm Thomas E.Cowan Lingen Huang Helmholtz-Zentrum Dresden-Rossendorf 01328 DresdenGermany Technische Universitat Dresden 01062 DresdenGermany

We investigate the dynamics of convergent shock compression in solid cylindrical targets irradiated by an ultrafast relativistic laser *** particle-in-cell simulations and coupled hydrodynamic simulations reveal that the compression process is initiated by both magnetic pressure and surface ablation associated with a strong transient surface return current with density of the order of 10^(17) A/m^(2) and lifetime of 100 *** results show that the dominant compression mechanism is governed by the plasma β,i.e.,the ratio of thermal pressure to magnetic *** targets with small radius and low atomic number Z,the magnetic pressure is the dominant shock compression *** to a scaling law,as the target radius and Z increase,the surface ablation pressure becomes the main mechanism generating convergent ***,an indirect experimental indication of shocked hydrogen compression is provided by optical shadowgraphy measurements of the evolution of the plasma expansion *** results presented here provide a novel basis for the generation of extremely high pressures exceeding Gbar(100 TPa)to enable the investigation of high-pressure physics using femtosecond J-level laser pulses,offering an alternative to nanosecond kJ-laser pulse-driven and pulsed power Z-pinch compression methods.

关键词： shock convergent return

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Small mammal community composition impacts bank vole (Clethrionomys glareolus) population dynamics and associated seroprevalence of Puumala orthohantavirus

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Integrative Zoology 2024年第1期19卷 52-65页

作者： Felicitas Maria BUJNOCH Daniela REIL Stephan DREWES Ulrike MROSENFELD Rainer G.ulrich Jens JACOB Christian IMHOLT Julius Kühn-Institute Federal Research Centre for Cultivated PlantsInstitute for Epidemiology and Pathogen DiagnosticsRodent ResearchMünsterGermany University of Münster Institute for Evolution and BiodiversityMünsterGermany Friedrich-Loeffler-Institut Federal Research Institute for Animal HealthInstitute of Novel and Emerging Infectious DiseasesGreifswald-Insel RiemsGermany

Rodents are important reservoirs for zoonotic pathogens that cause diseases in *** is hypoth-esized to be closely related to pathogen prevalence through multiple direct and indirect *** example,the presence of non-host species can reduce contact rates of the main reservoir host and thus reduce the risk of transmission(“dilution effect”).In addition,an overlap in ecological niches between two species could lead to increased interspecific competition,potentially limiting host densities and reducing density-dependent pathogen transmission *** this study,we investigated the relative impact of population-level regulation of direct and indirect drivers of the prevalence of Puumala orthohantavirus(PUUV)in bank voles(Clethrionomys glareolus)during years with high *** compiled data on small mammal community composition from four regions in Germany between 2010 and *** equation modeling revealed a strong seasonality in PUUV control mechanisms in bank *** abundance of shrews tended to have a negative relationship with host abundance,and host abundance positively influenced PUUV seroprevalence,while at the same time increasing the abundance of competing non-hosts like the wood mouse(Apodemus sylvaticus)and the yellow-neckedfield mouse(Apodemusflavicollis)were associated with reduced PUUV seroprevalence in the *** results indicate that for PUUV in bank voles,dilution is associated with increased interspecific *** pressures leading to the decline of Apodemus *** a specific habitat could lead to the amplification of mechanisms promoting PUUV transmission within the host populations.

关键词： bank vole biodiversity Puumala orthohantavirus small mammals

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Management and classification of the fracture of lateral process of talus:An overview and literature update

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World Journal of Clinical Cases 2024年第15期12卷 2487-2498页

作者： Chao-Qun Wang ulrich Stockle Sheng-Nan Dong Xu-Gui Li Ze-Xi Ling Department of Traumatic Orthopedics The Affiliated Hospital of Wuhan Sports UniversityWuhan 430079Hubei ProvinceChina Center of Musculoskeletal Surgery Berlin CharitéMedical University HospitalBerlin 13353Germany

Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or *** recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 *** this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.

关键词： Fracture of the lateral process of the talus Fracture of the talus Hindfoot injuries Intraarticular fracture Subtalar joint

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