1,722,003 research outputs found
Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant
No full textAbstract AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard (SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome (ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM, chlorine gas and radiation exposure studies
Abstract 5546: Improved gastrointestinal repair post irradiation with AEOL 10150
No full textAbstract
Background
Gastrointestinal toxicity, often manifested as ulceration and diarrhoea (mucositis) occurs following exposure to radiation and many chemotherapeutics. Potential treatments include prophylactic damage limitation or therapeutic/mitigatory wound repair dosing regimes. Treatments that are effective mitigators also have biodefence applications. In both the clinic or following nuclear terrorism effective agents may be given in combination with haematological therapies, in addition to standard supportive care agents.
Methods
AEOL 10150 [5,10,15,20-tetrakis(1,3-diethylimidazolium-2-yl) porphyrinato] manganese (III) pentachloride was administered to C57BL/6 male mice s.c. daily from 24hrs following a single dose of 13Gy total body X-irradiation. AEOL 10150 was administered at a 2x initial loading dose of 40 or 20mg/kg and then subsequently each day at 20 or 10mg/kg respectively. Animals were euthanized 4 and 6 days post irradiation and the number of regenerating small intestinal crypts measured. In a parallel study the levels diarrhoea and animal viability were measured animals exposed to 15Gy partial body X-irradiation (partially lead shielded to protect the bone marrow).
Results
Treatment with AEOL 10150 increased the number of surviving regenerating crypt observed in histological cross sections of the small intestine 4 days post irradiation. This was highly significant at both doses (p<0.001 for the 40/20mg/kg schedule and p=0.009 for the 20/10 mg/kg schedule). By day 6, where crypt numbers had increased from day 4, numbers were increased but not statistically significant. Levels of crypt fission, necessary to restore crypt numbers, were also increased. At the highest treatment dose animal mortality was only marginally reduced (p=0.115) but the severity and duration of observed diarrhoea was significantly reduced (p=0.021 and p=0.010 respectively).
Conclusion
AEOL 10150 demonstrated efficacy in both histological and physiological readouts of radiation induced gastrointestinal toxicity. Studies are currently ongoing to investigate whether other dosing schedules can further improve gastrointestinal repair.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5546.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Impact of Superoxide Dismutase Mimetic AEOL 10150 on the Endothelin System of Fischer 344 Rats.
No full textEndothelin-1 is a potent vasoconstrictor and mitogenic peptide involved in the regulation of vasomotor tone and maintenance of blood pressure. Oxidative stress activates the endothelin system, and is implicated in pulmonary and cardiovascular diseases including hypertension, congestive heart failure, and atherosclerosis. Superoxide dismutase mimetics designed with the aim of treating diseases that involve reactive oxygen species in their pathophysiology may exert a hypotensive effect, but effects on the endothelin system are unknown. Our objective was to determine the effect of the superoxide dismutase mimetic AEOL 10150 on the basal endothelin system in vivo. Male Fischer-344 rats were injected subcutaneously with 0, 2 or 5 mg/kg body weight of AEOL 10150 in saline. Plasma oxidative stress markers and endothelins (bigET-1, ET-1, ET-2, ET-3) as well as lung and heart endothelin/nitric oxide system gene expressions were measured using HPLC-Coularray, HPLC-Fluorescence and RT-PCR respectively. AEOL 10150 reduced (p<0.05) the circulating levels of isoprostane (-25%) and 3-nitrotyrosine (-50%) measured in plasma 2h and 24h after treatment, confirming delivery of a physiologically-relevant dose and the potent antioxidant activity of the drug. The reduction in markers of oxidative stress coincided with sustained 24h decrease (p<0.05) of plasma levels of ET-1 (-50%) and ET-3 (-10%). Expression of preproET-1 and endothelin converting enzyme-1 mRNA were not altered significantly in the lungs. However preproET-1 (not significant) and ECE-1 mRNA (p<0.05) were increased (10-25%) in the heart. Changes in the lungs included decrease (p<0.05) of mRNA for the ET-1 clearance receptor ETB and the vasoconstriction-signaling ETA receptor (-30%), and an early surge of inducible nitric oxide synthase expression followed by sustained decrease (-40% after 24 hours). The results indicate that interception of the endogenous physiological flux of reactive nitrogen species and reactive oxygen species in rats impacts the endothelin/nitric oxide system, supporting a homeostatic relationship between those systems
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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