94 research outputs found

    Receptor-Mediated Enhancement of Beta Adrenergic Drug Activity by Ascorbate In Vitro and In Vivo

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    RATIONALE: Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. OBJECTIVES: Extending this work to beta 2 adrenergic systems in vitro and in vivo. METHODS: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol with and without ascorbate was tested on horses with heaves and sheep with carbachol-induced bronchoconstriction. MEASUREMENTS: Binding constants for ascorbate binding to beta adrenergic receptor were derived from concentration-dependent spectral shifts. Dose- dependence curves were obtained for the relaxation of pre-contracted trachealis preparations due to beta agonists in the presence and absence of varied ascorbate. Tachyphylaxis and fade were also measured. Dose response curves were determined for the effect of albuterol plus-and-minus ascorbate on airway resistance in horses and sheep. MAIN RESULTS: Ascorbate binds to the beta 2 adrenergic receptor at physiological concentrations. The receptor recycles dehydroascorbate. Physiological and supra-physiological concentrations of ascorbate enhance submaximal epinephrine and isoproterenol relaxation of trachealis, producing a 3-10-fold increase in sensitivity, preventing tachyphylaxis, and reversing fade. In vivo, ascorbate improves albuterol's effect on heaves and produces a 10-fold enhancement of albuterol activity in "asthmatic" sheep. CONCLUSIONS: Ascorbate enhances beta-adrenergic activity via a novel receptor-mediated mechanism; increases potency and duration of beta adrenergic agonists effective in asthma and COPD; prevents tachyphylaxis; and reverses fade. These novel effects are probably caused by a novel mechanism involving phosphorylation of aminergic receptors and have clinical and drug-development applications

    Predicting mental imagery based BCI performance from personality, cognitive profile and neurophysiological patterns

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    Mental-Imagery based Brain-Computer Interfaces (MI-BCIs) allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphyā€” EEG), which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participantsā€™ BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities) were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participantsā€™ performance with a mean error of less than 3 points. This study determined how usersā€™ profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user

    Act In case of Depression: The evaluation of a care program to improve the detection and treatment of depression in nursing homes. Study Protocol

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    Contains fulltext : 95616.pdf (publisher's version ) (Open Access)BACKGROUND: The aim of this study is evaluating the (cost-) effectiveness of a multidisciplinary, evidence based care program to improve the management of depression in nursing home residents of somatic and dementia special care units. The care program is an evidence based standardization of the management of depression, including standardized use of measurement instruments and diagnostical methods, and protocolized psychosocial, psychological and pharmacological treatment. METHODS/DESIGN: In a 19-month longitudinal controlled study using a stepped wedge design, 14 somatic and 14 dementia special care units will implement the care program. All residents who give informed consent on the participating units will be included. Primary outcomes are the frequency of depression on the units and quality of life of residents on the units. The effect of the care program will be estimated using multilevel regression analysis. Secondary outcomes include accuracy of depression-detection in usual care, prevalence of depression-diagnosis in the intervention group, and response to treatment of depressed residents. An economic evaluation from a health care perspective will also be carried out. DISCUSSION: The care program is expected to be effective in reducing the frequency of depression and in increasing the quality of life of residents. The study will further provide insight in the cost-effectiveness of the care program. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1477

    Mineral phosphorus drives glacier algal blooms on the Greenland Ice Sheet

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    Melting of the Greenland Ice Sheet is a leading cause of land-ice mass loss and cryosphere-attributed sea level rise. Blooms of pigmented glacier iceĀ algae lower ice albedo and accelerate surface melting in the ice sheetā€™s southwest sector. Although glacier iceĀ algae cause up to 13% of the surface melting in this region, the controls on bloom development remain poorly understood. Here we show a direct link between mineral phosphorus in surface ice and glacier iceĀ algae biomass through the quantification of solid and fluid phase phosphorus reservoirs in surface habitats across the southwest ablation zone of the ice sheet. We demonstrate that nutrients from mineral dust likely drive glacier iceĀ algal growth, and thereby identify mineral dust as a secondary control on ice sheet melting.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Topological noetherianity for cubic polynomials

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    \u3cp\u3eLet P\u3csub\u3e3\u3c/sub\u3e(k\u3csup\u3eāˆž\u3c/sup\u3e) be the space of cubic polynomials in infinitely many variables over the algebraically closed field k (of characteristic ā‰  2, 3). We show that this space is GL\u3csub\u3eāˆž\u3c/sub\u3e-noetherian, meaning that any GL\u3csub\u3eāˆž\u3c/sub\u3e-stable Zariski closed subset is cut out by finitely many orbits of equations. Our method relies on a careful analysis of an invariant of cubics we introduce called q-rank. This result is motivated by recent work in representation stability, especially the theory of twisted commutative algebras. It is also connected to uniformity problems in commutative algebra in the vein of Stillmanā€™s conjecture.\u3c/p\u3

    Application of therapeutic plasma exchange in dogs with immuneā€mediated thrombocytopenia

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    Therapeutic plasma exchange (TPE) is an emerging treatment for dogs with immune-mediated diseases, but reports for treatment of immune-mediated thrombocytopenia (IMT) are lacking. These case reports illustrate the application of centrifugal TPE in 4 dogs with IMT. All dogs presented with severe hemorrhage requiring ā‰„1 blood transfusions, were unresponsive to conventional treatment or both. Dogs were treated with 3 sequential centrifugal TPE sessions, totaling 4.0 to 4.9 total plasma volumes exchanged per dog. In 3 dogs, TPE was associated with improvement in clinical manifestations of bleeding and platelet count in combination with immunosuppressive drugs. One dog was euthanized after 3 treatments because of persistent severe thrombocytopenia and hemorrhage. Preliminary observations indicate that TPE is safe and may be a useful adjunct in the management of IMT that is severe or refractory to traditional treatment
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