142 research outputs found

    Evaluation of propofol for repeated prolonged deep sedation in children undergoing proton radiation therapy

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    Background The aim of this study is to evaluate the safety and sufficiency of a fixed dose rate propofol infusion for repeated prolonged deep sedation in children for proton radiation therapy (PRT). Methods With ERB approval, we recorded anaesthesia monitoring data in children undergoing repeated prolonged propofol sedation for PRT. Sedation was introduced with a single bolus of i.v. midazolam 0.1 mg kg−1 followed by repeated small boluses of propofol until sufficient depth of sedation was obtained. Sedation was maintained with fixed dose rate propofol infusion of 10 mg kg−1 h−1 in all patients up to the end of the radiation procedure. Patient characteristics, number and duration of sedation, propofol induction dose, necessity to alter propofol infusion rate, and heart rate, mean arterial pressure, respiratory rate were noted at the end of the radiation procedure before cessation of the propofol infusion. Data are mean (sd) or range (median) as appropriate. Results Eighteen children aged from 1.4 to 4.2 yr (2.6 yr) had 27.6 (sd 2.0) (497 in total) radiation procedures within 44.1 (4.0) days lasting 55.7 (8.8) min. Propofol bolus dose for induction, monitoring, and positioning was 3.7 (1.0) mg kg−1. Propofol bolus requirements were quite stable over the successive weeks of treatment and variability was larger between individuals than over time. In none of the children did propofol infusion rate need to be changed from the pre-set 10 mg kg−1 h−1 flow rate because of haemodynamic state, respiratory conditions or inadequate anaesthesia. Conclusions Repeated prolonged deep sedation over several weeks in very young children using a fixed rate propofol infusion was safe and adequate for all patient

    Electron-Transfer Chemistry of Ru−Linker−(Heme)-Modified Myoglobin: Rapid Intraprotein Reduction of a Photogenerated Porphyrin Cation Radical

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    We report the synthesis and characterization of RuC7, a complex in which a heme is covalently attached to a [Ru(bpy)_3]^(2+) complex through a −(CH_2)_7− linker. Insertion of RuC7 into horse heart apomyoglobin gives RuC7Mb, a Ru(heme)−protein conjugate in which [Ru(bpy)_3]^(2+) emission is highly quenched. The rate of photoinduced electron transfer (ET) from the resting (Ru^(2+)/Fe^(3+)) to the transient (Ru^(3+)/Fe^(2+)) state of RuC7Mb is >10^8 s^(-1); the back ET rate (to regenerate Ru^(2+)/Fe^(3+)) is 1.4 × 10^7 s^(-1). Irreversible oxidative quenching by [Co(NH_3)_5Cl]^(2+) generates Ru^(3+)/Fe^(3+):  the Ru^(3+) complex then oxidizes the porphyrin to a cation radical (P^(•+)); in a subsequent step, P^(•+) oxidizes both Fe^(3+) (to give Fe^(IV)═O) and an amino acid residue. The rate of intramolecular reduction of P^(•+) is 9.8 × 10^3 s^(-1); the rate of ferryl formation is 2.9 × 10^3 s^(-1). Strong EPR signals attributable to tyrosine and tryptophan radicals were recorded after RuC7MbM^(3+) (M = Fe, Mn) was flash-quenched/frozen

    Characterization of reagent pencils for deposition of reagents onto paper-based microfluidic devices

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    Reagent pencils allow for solvent-free deposition of reagents onto paper-based microfluidic devices. The pencils are portable, easy to use, extend the shelf-life of reagents, and offer a platform for customizing diagnostic devices at the point of care. In this work, reagent pencils were characterized by measuring the wear resistance of pencil cores made from polyethylene glycols (PEGs) with different molecular weights and incorporating various concentrations of three different reagents using a standard pin abrasion test, as well as by measuring the efficiency of reagent delivery from the pencils to the test zones of paper-based microfluidic devices using absorption spectroscopy and digital image colorimetry. The molecular weight of the PEG, concentration of the reagent, and the molecular weight of the reagent were all found to have an inverse correlation with the wear of the pencil cores, but the amount of reagent delivered to the test zone of a device correlated most strongly with the concentration of the reagent in the pencil core. Up to 49% of the total reagent deposited on a device with a pencil was released into the test zone, compared to 58% for reagents deposited from a solution. The results suggest that reagent pencils can be prepared for a variety of reagents using PEGs with molecular weights in the range of 2000 to 6000 g/mol

    Reagent pencils: A new technique for solvent-free deposition of reagents onto paper-based microfluidic devices

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    Custom-made pencils containing reagents dispersed in a solid matrix were developed to enable rapid and solvent-free deposition of reagents onto membrane-based fluidic devices. The technique is as simple as drawing with the reagent pencils on a device. When aqueous samples are added to the device, the reagents dissolve from the pencil matrix and become available to react with analytes in the sample. Colorimetric glucose assays conducted on devices prepared using reagent pencils had comparable accuracy and precision to assays conducted on conventional devices prepared with reagents deposited from solution. Most importantly, sensitive reagents, such as enzymes, are stable in the pencils under ambient conditions, and no significant decrease in the activity of the enzyme horseradish peroxidase stored in a pencil was observed after 63 days. Reagent pencils offer a new option for preparing and customizing diagnostic tests at the point of care without the need for specialized equipment

    The relationship between redox enzyme activity and electrochemical potential—cellular and mechanistic implications from protein film electrochemistry

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    In protein film electrochemistry a redox protein of interest is studied as an electroactive film adsorbed on an electrode surface. For redox enzymes this configuration allows quantification of the relationship between catalytic activity and electrochemical potential. Considered as a function of enzyme environment, i.e., pH, substrate concentration etc., the activity–potential relationship provides a fingerprint of activity unique to a given enzyme. Here we consider the nature of the activity–potential relationship in terms of both its cellular impact and its origin in the structure and catalytic mechanism of the enzyme. We propose that the activity–potential relationship of a redox enzyme is tuned to facilitate cellular function and highlight opportunities to test this hypothesis through computational, structural, biochemical and cellular studies

    The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols

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    It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme. Like NO, HNO activation appears to occur via interaction with the regulatory ferrous heme on sGC. Somewhat unexpectedly, HNO does not activate the ferric form of the enzyme. Finally, HNO-mediated cysteine thiol modification appears to also affect enzyme activity leading to inhibition. Thus, sGC activity can be regulated by HNO via interactions at both the regulatory heme and cysteine thiols

    HNO Binding in a Heme Protein: Structures, Spectroscopic Properties, and Stabilities

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    HNO can interact with numerous heme proteins, but atomic level structures are largely unknown. In this work, various structural models for the first stable HNO heme protein complex, MbHNO (Mb, myoglobin), were examined by quantum chemical calculations. This investigation led to the discovery of two novel structural models that can excellently reproduce numerous experimental spectroscopic properties. They are also the first atomic level structures that can account for the experimentally observed high stabilities. These two models involve two distal His conformations as reported previously for MbCNR and MbNO. However, a unique dual hydrogen bonding feature of the HNO binding was not reported before in heme protein complexes with other small molecules such as CO, NO, and O2. These results shall facilitate investigations of HNO bindings in other heme proteins

    A review of soil NO transformation: associated processes and possible physiological significance on organisms

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    NO emissions from soils and ecosystems are of outstanding importance for atmospheric chemistry. Here we review the current knowledge on processes involved in the formation and consumption of NO in soils, the importance of NO for the physiological functioning of different organisms, and for inter- and intra-species signaling and competition, e.g. in the rooting zone between microbes and plants. We also show that prokaryotes and eukaryotes are able to produce NO by multiple pathways and that unspecific enzymo-oxidative mechanisms of NO production are likely to occur in soils. Nitric oxide production in soils is not only linked to NO production by nitrifying and denitrifying microorganisms, but also linked to extracellular enzymes from a wide range of microorganisms. Further investigations are needed to clarify molecular mechanisms of NO production and consumption, its controlling factors, and the significance of NO as a regulator for microbial, animal and plant processes. Such process understanding is required to elucidate the importance of soils as sources (and sinks) for atmospheric NO
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