			Home About us Contact

Sufficient Stability (sufficient + stability)

Distribution by Scientific Domains

Medical Sciences	50%
Chemistry	50%

Selected Abstracts

Development and Validation of a Mass Casualty Conceptual Model

JOURNAL OF NURSING SCHOLARSHIP, Issue 1 2010
CWOCN, Joan M. Culley RN
Abstract Purpose: To develop and validate a conceptual model that provides a framework for the development and evaluation of information systems for mass casualty events. Design: The model was designed based on extant literature and existing theoretical models. A purposeful sample of 18 experts validated the model. Open-ended questions, as well as a 7-point Likert scale, were used to measure expert consensus on the importance of each construct and its relationship in the model and the usefulness of the model to future research. Methods: Computer-mediated applications were used to facilitate a modified Delphi technique through which a panel of experts provided validation for the conceptual model. Rounds of questions continued until consensus was reached, as measured by an interquartile range (no more than 1 scale point for each item); stability (change in the distribution of responses less than 15% between rounds); and percent agreement (70% or greater) for indicator questions. Findings: Two rounds of the Delphi process were needed to satisfy the criteria for consensus or stability related to the constructs, relationships, and indicators in the model. The panel reached consensus or sufficient stability to retain all 10 constructs, 9 relationships, and 39 of 44 indicators. Experts viewed the model as useful (mean of 5.3 on a 7-point scale). Conclusions: Validation of the model provides the first step in understanding the context in which mass casualty events take place and identifying variables that impact outcomes of care. Clinical Relevance: This study provides a foundation for understanding the complexity of mass casualty care, the roles that nurses play in mass casualty events, and factors that must be considered in designing and evaluating information-communication systems to support effective triage under these conditions. [source]

Side chain contributions to the interconversion of the topological isomers of guanylin-like peptides

JOURNAL OF PEPTIDE SCIENCE, Issue 6 2005
Dr Axel Schulz
Abstract The peptide hormones guanylin and uroguanylin are ligands of the intestinal guanylyl cyclase-C (GC-C) that is involved in the regulation of epithelial water and electrolyte transport. The small peptides contain 15 and 16 amino acids, respectively, and two disulfide bonds with a 1,3/2,4 connectivity. This structural feature causes the unique existence of two topological isoforms for each peptide in an approximate 3:2 ratio, with only one of the isoforms exhibiting GC-C-activating potential. The two uroguanylin isomers can be separated by HPLC and are of sufficient stability to be studied separately at ambient temperatures while the two guanylin isomers are rapidly interconverting even at low temperatures. Both isomers show clearly distinguishable 1H chemical shifts. To investigate the influence of certain amino acid side chains on this isomerism and interconversion kinetics, derivatives of guanylin and uroguanylin (L -alanine scan and chimeric peptides) were designed and synthesized by Fmoc solid-phase chemistry and compared by HPLC and 2D 1H NMR spectroscopy. Amino acid residues with the most significant effects on the interconversion kinetics were predominantly identified in the COOH-terminal part of both peptides, whereas amino acids in the central part of the peptides only moderately affected the interconversion. Thus, the conformational conversion among the isomers of both peptides is under the control of a COOH-terminal sterical hindrance, providing a detailed model for this dynamic isomerism. Our results demonstrate that kinetic control of the interconversion process can be achieved by the introduction of side chains with a defined sterical profile at suitable sequence positions. This is of potential impact for the future development of GC-C peptide agonists and antagonists. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source]

Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits

ACTA OPHTHALMOLOGICA, Issue 3 2010
Thorsteinn Loftsson
Abstract. Purpose:, This study aimed to develop low-viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits. Methods:, Aqueous eyedrops with hydroxypropyl-,-cyclodextrin containing 0.01,2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments ± standard error of the mean) are expressed as the change from baseline (24.7 ± 3.3 mmHg). Results:, Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf-life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 ± 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 ± 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10,22 hours after administration and duration of up to 32 hours. Conclusions:, Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low-viscosity aqueous eyedrop formulations. [source]

Discovery of Potent, Orally Bioavailable Small-Molecule Inhibitors of the Human CCR2 Receptor

CHEMMEDCHEM, Issue 4 2008
Julien Doyon Dr.
Abstract We recently reported the discovery of a series of 2-thioimidazoles as CCR2 antagonists. The most potent molecules of this series, the 4,5-diesters, were rapidly hydrolyzed to the inactive acids and were found to be metabolically unstable. Herein we describe the synthesis of a number of analogues with heterocyclic bioisosteric replacements of the ester group(s). Small 5-membered heterocyclic substituents at the 4-position gave highly potent CCR2 antagonists. Hydrolysis of the 5-ester is diminished, thus imparting these compounds with sufficient stability and systemic exposure after oral administration to warrant further study of the in,vivo pharmacology of these functional CCR2 inhibitors. [source]