1,723,697 research outputs found
Pharmacokinetics and pharmacokinetic-dynamic relationship between rapacuronium (Org 9487) and its 3-desacetyl metabolite (Org 9488)
No full textRapacuronium (Org 9487) is a rapid-onset and short- to intermediate-acting muscle relaxant. Its 3-desacetyl metabolite, Org 9488, also exerts neuromuscular-blocking activity that. may became apparent after prolonged maintenance of relaxation with rapacuronium. In this study, the pharmacokinetic behavior (n = 7) of this metabolite and the pharmacokinetic/pharmacodynamic (PK/PD) relationship of rapacuronium (n = 10) and Org 9488 (n = 7) were investigated in humans. Similar protocols were used for three study groups regarding the anesthetic technique, blood and urine sampling, and pharmacokinetic and PK/PD analyses. The time course of action was measured mechanomyographically using the adductor pollicis muscle. The median clearance of rapacuronium was 7.28 mL.kg(-1).min(-1) with. an excretion fraction in the urine of 6.2%. The clearance (studied in two groups) of Org = 9488 was 128 and 1.06 mL.kg(-1).min(-1) with an excretion fraction in the urine of 51.9% and 53.5%, respectively. The median rate constant of transport between plasma and the biophase of rapacuronium (0.449 min(-1)) is markedly larger than that for Org 9488 (0.105 min(-1)). The modeled concentration in the biophase at 50% effect as a measure of potency is higher for rapacuronium (4.70 mu g/mL) than for Org 9488 (1.83 mu g/mL). The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium. Implications: We investigated the concentration-time-effect relationship of the relaxant rapacuronium and the contribution of its metabolite. Clearance, rate constant of transport between plasma and the biophase, and modeled concentration in the biophase at 50% effect of rapacuronium are consistent with its rapid onset and short to intermediate duration. The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium.</p
Pharmacokinetics and pharmacokinetic-dynamic relationship between rapacuronium (Org 9487) and its 3-desacetyl metabolite (Org 9488)
No full textRapacuronium (Org 9487) is a rapid-onset and short- to intermediate-acting muscle relaxant. Its 3-desacetyl metabolite, Org 9488, also exerts neuromuscular-blocking activity that. may became apparent after prolonged maintenance of relaxation with rapacuronium. In this study, the pharmacokinetic behavior (n = 7) of this metabolite and the pharmacokinetic/pharmacodynamic (PK/PD) relationship of rapacuronium (n = 10) and Org 9488 (n = 7) were investigated in humans. Similar protocols were used for three study groups regarding the anesthetic technique, blood and urine sampling, and pharmacokinetic and PK/PD analyses. The time course of action was measured mechanomyographically using the adductor pollicis muscle. The median clearance of rapacuronium was 7.28 mL.kg(-1).min(-1) with. an excretion fraction in the urine of 6.2%. The clearance (studied in two groups) of Org = 9488 was 128 and 1.06 mL.kg(-1).min(-1) with an excretion fraction in the urine of 51.9% and 53.5%, respectively. The median rate constant of transport between plasma and the biophase of rapacuronium (0.449 min(-1)) is markedly larger than that for Org 9488 (0.105 min(-1)). The modeled concentration in the biophase at 50% effect as a measure of potency is higher for rapacuronium (4.70 mu g/mL) than for Org 9488 (1.83 mu g/mL). The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium. Implications: We investigated the concentration-time-effect relationship of the relaxant rapacuronium and the contribution of its metabolite. Clearance, rate constant of transport between plasma and the biophase, and modeled concentration in the biophase at 50% effect of rapacuronium are consistent with its rapid onset and short to intermediate duration. The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium.</p
Pharmacokinetics and pharmacokinetic-dynamic relationship between rapacuronium (Org 9487) and its 3-desacetyl metabolite (Org 9488)
No full textRapacuronium (Org 9487) is a rapid-onset and short- to intermediate-acting muscle relaxant. Its 3-desacetyl metabolite, Org 9488, also exerts neuromuscular-blocking activity that. may became apparent after prolonged maintenance of relaxation with rapacuronium. In this study, the pharmacokinetic behavior (n = 7) of this metabolite and the pharmacokinetic/pharmacodynamic (PK/PD) relationship of rapacuronium (n = 10) and Org 9488 (n = 7) were investigated in humans. Similar protocols were used for three study groups regarding the anesthetic technique, blood and urine sampling, and pharmacokinetic and PK/PD analyses. The time course of action was measured mechanomyographically using the adductor pollicis muscle. The median clearance of rapacuronium was 7.28 mL.kg(-1).min(-1) with. an excretion fraction in the urine of 6.2%. The clearance (studied in two groups) of Org = 9488 was 128 and 1.06 mL.kg(-1).min(-1) with an excretion fraction in the urine of 51.9% and 53.5%, respectively. The median rate constant of transport between plasma and the biophase of rapacuronium (0.449 min(-1)) is markedly larger than that for Org 9488 (0.105 min(-1)). The modeled concentration in the biophase at 50% effect as a measure of potency is higher for rapacuronium (4.70 mu g/mL) than for Org 9488 (1.83 mu g/mL). The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium. Implications: We investigated the concentration-time-effect relationship of the relaxant rapacuronium and the contribution of its metabolite. Clearance, rate constant of transport between plasma and the biophase, and modeled concentration in the biophase at 50% effect of rapacuronium are consistent with its rapid onset and short to intermediate duration. The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium
Hämodynamische und molekulare Effekte des eNOS-Transkriptionsenhancers AVE 9488 bei gesunden Ratten und Ratten mit sekundär biliärer Leberzirrhose
Get PDFNO spielt eine Schlüsselrolle als Vasodilatator bei portaler Hypertension [159]. Konventionelle Therapeutika wirken entweder der erhöhten splanchnischen Durchblutung entgegen oder steigern die NO-Freisetzung in der Leber. Eine systemische Hypotonie durch NO-Donoren ist eine unerwünschte Nebenwirkung. Zur Senkung des portalen Hypertonus haben sich Monotherapien mit nicht-selektiven β-Blockern wie auch die Kombinationstherapie von β-Blocker und Nitrat bewährt [49]. Als neue experimentelle Therapiealternativen werden NOS-Gentransfer- Experimente [132,162], Statine [163] oder der selektive NO-Donor NCX-1000 [40,81] in Erwägung gezogen. Durch den eNOS-Transkriptionsenhancer AVE 9488 zeigen sich in der Real Time PCR auf molekularer Ebene erhöhte eNOS mRNA-Steady-State-Level in der Leber (3,6-fache Zunahme, p=0,002). Im Unterschied dazu sind keine Veränderungen in den eNOS mRNA-Steady-State- Level im splanchnischen und systemischen Gefäßsystem festzustellen. Die Immunoblotanalyse zeigt ebenfalls eine vermehrte eNOS-Synthese in der Leber bei nicht erhöhtem eNOS-Protein in den Gefäßen des Splanchnikus und des Systemkreislaufs. Die intrahepatische Phosphorylierung von VASP als indirektem Marker der NOS-Aktivität wird durch AVE 9488 erhöht. Die In-situ- Leberperfusion zeigt eine signifikante Pfortaderdrucksteigerung bei NOS-Blockade durch LNAME (60% vs. 100%, p Die orale Behandlung von BDL-Ratten mit AVE 9488 bewirkt eine signifikante Erhöhung der NOS-3-mRNA und des Proteins in der Leber. Die effektive Pfortaderdrucksenkung und die Erniedrigung des intrahepatischen und splanchnischen Widerstandes durch eine vermehrte NOVerfügbarkeit ohne Einfluss auf den systemischen Blutdruck sind erwünschte Therapieziele, die durch den eNOS-Transkriptionsenhancer AVE 9488 erreicht werden.</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
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
- …
