301 research outputs found

    Reactive Oxygen Species Generation in Human Cells by a Novel Magnetic Resonance Imaging Contrast Agent

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    The novel positive-contrast magnetic resonance imaging (MRI) marker C4 consists of an aqueous solution of cobalt chloride (CoCl 2 ) complexed with the chelator N-acetylcysteine (NAC). We evaluated whether the presence of C4 or its components would produce reactive oxygen species (ROS, including hydroxyl, peroxyl, or other reactive oxygen species) in cultured cells. Human cancer or normal cells were incubated with 1% (w/v) CoCl 2 ·6H 2 O or 2% NAC or a combination of both (1% CoCl 2 ·6H 2 O: 2% NAC in an aqueous solution, abbreviated as Co: NAC) in the presence or absence of H 2 O 2 . Intracellular ROS levels were measured and quantified by change in relative fluorescence units. Student\u27s t-tests were used. In all cell lines exposed to 1000 μM H 2 O 2 , the Co: NAC led to ≥94.7% suppression of ROS at 5 minutes and completely suppressed ROS at 60 and 90 minutes; NAC suppressed ROS by ≥76.6% at 5 minutes and by ≥94.5% at 90 minutes; and CoCl 2 ·6H 2 O suppressed ROS by ≥37.2% at 30 minutes and by ≥48.6% at 90 minutes. These results demonstrate that neither Co: NAC nor its components generated ROS; rather, they suppressed ROS production in cultured cells, suggesting that C4 would not enhance ROS production in clinical use

    Effects of Pramipexole on Impulsive Choice in Male Wistar Rats

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    This article may not exactly replicate the final version published in the APA journal. It is not the copy of record.Clinical reports, primarily with Parkinson’s patients, note an association between the prescribed use of pramipexole (and other direct-acting dopamine agonist medications) and impulse control disorders, particularly pathological gambling. Two experiments examined the effects of acute pramipexole on rats’ impulsive choices where impulsivity was defined as selecting a smaller-sooner over a larger-later food reward. In Experiment 1, pramipexole (0.1 to 0.3 mg/kg) significantly increased impulsive choices in a condition in which few impulsive choices were made during a stable baseline. In a control condition, in which impulsive choices predominated during baseline, pramipexole did not significantly change the same rats’ choices. Experiment 2 explored a wider range of doses (0.01 to 0.3 mg/kg) using a choice procedure in which delays to the larger-later reinforcer delivery increased across trial blocks within each session. At the doses used in Experiment 1, pramipexole shifted choice toward indifference regardless of the operative delay. At lower doses of pramipexole (0.01 & 0.03 mg/kg), a trend toward more impulsive choice was observed at the 0.03 mg/kg dose. The difference in outcomes across experiments may be due to the more complex discriminations required in Experiment 2; i.e., multiple discriminations between changing delays within each session

    A review of quantitative structure-activity relationship modelling approaches to predict the toxicity of mixtures

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    Exposure to chemicals generally occurs in the form of mixtures. However, the great majority of the toxicity data, upon which chemical safety decisions are based, relate only to single compounds. It is currently unfeasible to test a fully representative proportion of mixtures for potential harmful effects and, as such, in silico modelling provides a practical solution to inform safety assessment. Traditional methodologies for deriving estimations of mixture effects, exemplified by principles such as concentration addition (CA) and independent action (IA), are limited as regards the scope of chemical combinations to which they can reliably be applied. Development of appropriate quantitative structure-activity relationships (QSARs) has been put forward as a solution to the shortcomings present within these techniques – allowing for the potential formulation of versatile predictive tools capable of capturing the activities of a full contingent of possible mixtures. This review addresses the current state-of-the-art as regards application of QSAR towards mixture toxicity, discussing the challenges inherent in the task, whilst considering the strengths and limitations of existing approaches. Forty studies are examined within – through reference to several characteristic elements including the nature of the chemicals and endpoints modelled, the form of descriptors adopted, and the principles behind the statistical techniques employed. Recommendations are in turn provided for practices which may assist in further advancing the field, most notably with regards to ensuring confidence in the acquired predictions.publishedVersio

    High quality waveguides for the mid-infrared wavelength range in a silicon-on-sapphire platform

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    We report record low loss silicon-on-sapphire nanowires for applications to mid infrared optics. We achieve propagation losses as low as 0.8dB/cm at 1550nm, 1.1 to 1.4dB/cm at 2080nm and < 2dB/cm at = 5.18 microns.Comment: 9 pages, 6 figures, 18 reference

    Toxicity Evaluation of a Novel Magnetic Resonance Imaging Marker CoCl2-N-Acetylcysteine in Rats

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    C4 (cobalt dichloride-N-acetylcysteine [1% CoCl 2 :2% NAC]) is a novel magnetic resonance imaging contrast marker that facilitates visualization of implanted radioactive seeds in cancer brachytherapy. We evaluated the toxicity of C4. Rats were assigned to control (0% CoCl 2 :NAC), low-dose (0.1% CoCl 2 :2% NAC), reference-dose (C4), and high-dose (10% CoCl 2 :2% NAC) groups. Agent was injected into the left quadriceps femoris muscle of the rats. Endpoints were organ and body weights, hematology, and serum chemistry and histopathologic changes of tissues at 48 hours and 28 and 63 days after dosing. Student\u27s t tests were used. No abnormalities in clinical signs, terminal body and organ weights, or hematologic and serum chemistry were noted, and no gross or histopathologic lesions of systemic tissue toxicity were found in any treatment group at any time point studied. At the site of injection, concentration-dependent acute responses were observed in all treatment groups at 48 hours after dosing and were recovered by 28 days. No myofiber degeneration or necrosis was observed at 28 or 63 days in any group. In conclusion, a single intramuscular dose of C4 produced no acute or chronic systemic toxicity or inflammation in rats, suggesting that C4 may be toxicologically safe for clinical use in cancer brachytherapy

    Using a novel biologging approach to assess how different handling practices influence the post-release behaviour of Northern Pike across a wide range of body sizes

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    There is a growing body of research focused on how angled fish respond to catch-and-release (C&R). However, most of those studies do not span a wide range of body sizes for the targeted species. Physical injury and physiological responses to C&R can be size-dependent, and methods used for landing fish of different sizes vary. As such, studying the response to C&R across a range of fish sizes may help inform best practices that improve outcomes for released fish. Northern Pike (Esox lucius) widely ranges in body size. Anglers may land them by hand, cradle, or net, and they are often released voluntarily or to comply with regulations. We angled 25 Northern Pike (total length 620–1030 mm) from one population and recorded fight, handling, and unhooking times across landing methods (i.e., hand, cradle, net). Prior to release, a pop-off biologging package was temporarily affixed to each fish to monitor locomotor activity, depth, and water temperature during a 12-h period post-release to understand how the interaction of landing method and body size influenced post-release behaviour and short-term fate. Fight and handling time increased with increasing body size. Northern Pike landed with a cradle or net had shorter fight times but longer handling times, compared to fish landed by hand. Post-release locomotor activity was greater for larger fish and those landed with a net. Fish 775mm landed by hand had reduced locomotor activity compared to fish landed with a net. There was no post-release mortality observed. Collectively, anglers should use a net for Northern Pike >775 mm to avoid long fight times and reduce post-release exhaustion, but also attempt to reduce the extent of handling associated with fish landed by net

    Reactive Oxygen Species Generation in Human Cells by a Novel Magnetic Resonance Imaging Contrast Agent

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    The novel positive-contrast magnetic resonance imaging (MRI) marker C4 consists of an aqueous solution of cobalt chloride (CoCl2) complexed with the chelator N-acetylcysteine (NAC). We evaluated whether the presence of C4 or its components would produce reactive oxygen species (ROS, including hydroxyl, peroxyl, or other reactive oxygen species) in cultured cells. Human cancer or normal cells were incubated with 1% (w/v) CoCl2·6H2O or 2% NAC or a combination of both (1% CoCl2·6H2O : 2% NAC in an aqueous solution, abbreviated as Co : NAC) in the presence or absence of H2O2. Intracellular ROS levels were measured and quantified by change in relative fluorescence units. Student’s t-tests were used. In all cell lines exposed to 1000 μM H2O2, the Co : NAC led to ≥94.7% suppression of ROS at 5 minutes and completely suppressed ROS at 60 and 90 minutes; NAC suppressed ROS by ≥76.6% at 5 minutes and by ≥94.5% at 90 minutes; and CoCl2·6H2O suppressed ROS by ≥37.2% at 30 minutes and by ≥48.6% at 90 minutes. These results demonstrate that neither Co : NAC nor its components generated ROS; rather, they suppressed ROS production in cultured cells, suggesting that C4 would not enhance ROS production in clinical use

    Cyclone Hard X-Ray Observatory

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    In response to the recent NASA-SMEX Announcement of Opportunity, our collaboration proposed Cyclone, the Cyclotron/Nuclear Explorer. Cyclone is a broadband pointed astrophysical observatory, combining the highest spectral resolutions (E/(Delta) E approximately 30 - 300) and angular resolutions (15') achieved in the optimized hard X-ray range (10 - 200 keV). The instrument consists of 19 co-aligned rotation modulation collimator (RMC) telescopes, each with a high spectral resolution, 6-cm diameter germanium detector (GeD) covering energies from 3 keV to 600 keV. Both the optics and detectors are actively shielded with 15-mm BGO to gain low background an high sensitivity to astrophysical sources. A 550-km altitude, circular equatorial orbit also minimizes background. Building strongly upon instrumental heritage from the High-Energy Solar Spectroscopic Imager (HESSI) program, Cyclone would be ready for launch by September 2003. The instrument design and expected performance are discussed, as well as a brief overview of scientific goals
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