Alien Registration- Davis, Myrtle (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24421/thumbnail.jp

Assessing functional and structural cardiotoxicity in cultured human iPSC-cardiomyocytes in a single plate format

Présentation PosterInternational audienceA comprehensive profiling of cardiotoxicity early in drug discovery and development can aid in reducing late-stage attrition and establishing risk-mitigation strategies during clinical development. In most cases, multiple assay platforms and instrument-specified plate formats are required for this type of approach. In this study, we evaluated both functional and structural endpoints associated with cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in a single 384-well plate. We measured intracellular Ca2+ transit, caspase 3/7 activation and plasma membrane permeabilization sequentially in the same plate via a series of assay readouts. A set of cardiac ion channel modulators (dofetilide, sotalol, nifedipine and mexiletine) and chemotherapeutics (tamoxifen, nilotinib, sunitinib and doxorubicin) was tested at clinically relevant concentrations for effects on intracellular Ca 2+ transits after a short-term (30 minutes) exposure, and plasma membrane permeabilization and caspase 3/7 activation after a long-term (72 hours) exposure. Intracellular Ca2+ transits were monitored by fluorescent images taken with a high-speed camera in beating cardiomyocytes loaded with Cal520® Ca2+ dye, permeabilized plasma membrane (for dead-cell detection) was identified with live-stain DRAQ7TM nuclear dye and activation of caspase 3/7 was determined biochemically with the Caspase-Glo® 3/7 Assay kit. Multiple endpoints derived from Ca 2+ transits, including beat rate, calcium transit duration (CTD) measured at 30% or 90% from peak and corrected by inter-peak interval (IPI), along with CTD triangulation, beat rhythm, short- or long-term variability of CTD90 and IPI Poincaré plots, were used to assess drug effects on intracellular Ca2+ cycling and arrhythmogenicity. Increases in positive nuclear staining for DRAQ7TM and caspase 3/7 activity represented structural cardiotoxicity. We found that increased CTD triangulation, development of arrhythmic events and both the short- and long-term variability of CTD90 or IPI were robust indicators of functional effects. Positive nuclear staining for DRAQ7TM was a robust indicator of structural effects. Accordingly, dofetilide and sotalol were identified as primarily arrhythmogenic, doxorubicin was primarily structurally toxic, while nilotinib and sunitinib were both arrhythmogenic and structurally toxic. The use of these endpoints in a single plate format simplifies the cardiotoxicity assessment and does not require multiple cell plates for measurements

Alien Registration- Davis, Myrtle (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24421/thumbnail.jp

Myrtle and Francis Davis Folder

32 pages of family history documents containing and related to Myrtle E Davis; Bud Francis Davis; Carol Davis; Oscar Dell Davis - including: family tree; written history; Oral History; obi

The Mechanism of Cyanohydroxybutene Induced Glutathione Elevation: The Role of Gamma-Glutamylcysteine Synthetase

138 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1992.Cyanohydroxybutene (CHB; 200 mg/kg po) causes a 2- and 7-fold elevation in glutathione (GSH) in liver and pancreas, respectively. The mechanism of elevation is currently unknown. In an attempt to identify the mechanism of this GSH induction, the effect of CHB on hepatic and pancreatic $\gamma$-glutamylcysteine synthetase (GCS) activity, formation in vitro of a glutathione-S-transferase (GST) catalyzed adduct, the effect of CHB on hepatic and pancreatic cysteine equivalents (cysteine, cystine, and cysteinylglycine), and the acute effect of CHB on expression of the hepatic mRNA for $\gamma$-glutamylcysteine synthetase (GCS) were investigated. The results of these studies suggest that the mechanism of CHB-mediated induction of GSH involves an increase in GCS mRNA producing an increase in GCS enzyme and thereby increasing GSH synthesis. This mechanism and the subsequent GSH elevation may have possible therapeutic and prophylactic implications.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Preparing Nutritious Meals at Minimal Cost

Excerpt from the report Introduction: This publication, Preparing Nutritious Meals at Minimal Cost, provides information for educators and other information multipliers to help families on a tight budget prepare foods for a healthful diet. Two sample meal plans, tips for nutritious meals at minimal cost, and a resource list for additional information are included. Each meal plan consists of a weekly menu, 20 laboratory-tested recipes, and a food list. Each daily menu consists of three meals (breakfast, lunch, and dinner) and usually a snack

Enhancing quality of life as a goal for anticancer therapeutics

Translational cancer research requires a quality-of-life-driven agenda