1,770,950 research outputs found
Strategies to Reduce Morphine Tolerance in Cancer: Evaluation of the Bifunctional Opioid UFP-505
No full textMorphine is a gold-standard analgesic acting at MOP (μ) opioid receptors, producing analgesia and tolerance when administered chronically to patients (e.g.,cancer patients). If DOP (δ) opioid receptors are blocked at the same time that MOP is activated then analgesia with reduced tolerance results. UFP-505 (H-Dmt-Tic-Gly-NH-Bzl) is a synthetic pseudopeptide that interacts with MOP and DOP receptors (bifunctional). In a series of different models, we have characterized the pharmacological profile of UFP- 505 and we evaluated its antinociceptive properties in vivo.
In Chinese Hamster Ovary (CHO) cells stably expressing human MOP or DOP receptors, UFP-505 presented a full agonism and ultra-low partial agonism respectively.
UFP-505 caused a concentration-dependent internalization of MOP receptors, in contrast to morphine. Additionally, UFP-505 caused DOP receptor internalization similar to the full DOP agonist DPDPE. In a series of tail-flick assays using Wistar rats, acute intrathecal (i.t.) 10nmol UFP-505 produced strong antinociception, similar to 10nmol i.t. morphine. After 3 days of repeated administration, UFP-505 did not produce antinociceptive tolerance, in contrast to morphine. In neuronal tissue of treated animals, UFP-505 caused varying changes to opioid receptor mRNA levels, similar to morphine.
In the same model, UFP-505 induced MOP and DOP receptor internalization, whereas morphine failed to internalize the MOP receptors. UFP-505 also induced the internalization of MOP and DOP receptors in a novel CHO cell line stably expressing both receptors (produced as part of this project), in contrast to morphine.
Collectively this thesis has made a significant contribution to the field in that: 1) an extensive pharmacological in vitro and in vivo characterization is made; 2) a MOPagonist/DOP-partial agonist is shown to produce strong antinociception with no tolerance.
Further work on bifunctional opioids may lead to a better understanding of the mechanisms of analgesic tolerance and ligands like UFP-505 are good examples of prototypes for further development
Strategies to Reduce Morphine Tolerance in Cancer: Evaluation of the Bifunctional Opioid UFP-505
No full textMorphine is a gold-standard analgesic acting at MOP (μ) opioid receptors, producing analgesia and tolerance when administered chronically to patients (e.g.,cancer patients). If DOP (δ) opioid receptors are blocked at the same time that MOP is activated then analgesia with reduced tolerance results. UFP-505 (H-Dmt-Tic-Gly-NH-Bzl) is a synthetic pseudopeptide that interacts with MOP and DOP receptors (bifunctional). In a series of different models, we have characterized the pharmacological profile of UFP- 505 and we evaluated its antinociceptive properties in vivo. In Chinese Hamster Ovary (CHO) cells stably expressing human MOP or DOP receptors, UFP-505 presented a full agonism and ultra-low partial agonism respectively. UFP-505 caused a concentration-dependent internalization of MOP receptors, in contrast to morphine. Additionally, UFP-505 caused DOP receptor internalization similar to the full DOP agonist DPDPE. In a series of tail-flick assays using Wistar rats, acute intrathecal (i.t.) 10nmol UFP-505 produced strong antinociception, similar to 10nmol i.t. morphine. After 3 days of repeated administration, UFP-505 did not produce antinociceptive tolerance, in contrast to morphine. In neuronal tissue of treated animals, UFP-505 caused varying changes to opioid receptor mRNA levels, similar to morphine. In the same model, UFP-505 induced MOP and DOP receptor internalization, whereas morphine failed to internalize the MOP receptors. UFP-505 also induced the internalization of MOP and DOP receptors in a novel CHO cell line stably expressing both receptors (produced as part of this project), in contrast to morphine. Collectively this thesis has made a significant contribution to the field in that: 1) an extensive pharmacological in vitro and in vivo characterization is made; 2) a MOPagonist/DOP-partial agonist is shown to produce strong antinociception with no tolerance. Further work on bifunctional opioids may lead to a better understanding of the mechanisms of analgesic tolerance and ligands like UFP-505 are good examples of prototypes for further development
Participant 505 Community Conversations Essay
No full textIn this essay, Participant 505 eulogizes the handshake. The participant reminisces about their father's famous handshake and the impact it had on others. The participant states that they adopted this handshake, and taught the same method to their children. They say that the handshake has been replaced by other types of greetings during the pandemic, but that none of them are adequate substitutes.New Jersey Department of Healt
The Design of Egyptian 505
No full textIn 1965 the Visual Graphics Corporation organized an international competition for new typeface designs. The author directed his typography class at the Kungstgewerbeschule, Basel, Switzerland, in designing a class-project entry: Egyptian 505. The students’ training for type design is described together with the specific development of Egyptian 505 for photocomposition. Art school education for script and type design is discussed
Resolución UNRN N° 505/2009. Otorga equivalencia. No otorgar equivalencia.
No full textFil: Universidad Nacional de Río Negro (U). Universidad Nacional de Río Negro. Río Negro, ArgentinaResolución UNRN N° 505/2009. Otorga equivalencia. No otorgar equivalencia.fals
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
(Table 1) Total and organic carbon in sediments at DSDP Holes 69-504 and 69-505
No full textSediments from Deep Sea Drilling Project Sites 504 and 505 near the Costa Rica Rift were examined by thermal methods. It was found that production index (P.I.) values, which measure the degree of thermal hydrocarbon generation in the sediment, were slightly different for the two sites when compared for sediments with similar types of organic matter. Highly burrowed sections of these immature sediments gave anomalously low values of pyrolyzable hydrocarbons, suggesting production of inert organic carbon by purely biological processes. Organic carbon levels correlate with pyrolyzable hydrocarbons at both sites and show that samples with less than 1 % organic carbon are inert to hydrocarbon generation under any conditions of time and temperature
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