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Kinetic Constants and Sample-to-Sample Variation in the Rate of Metabolism of two or more Substrates for Human Liver Microsomal CYP1A2, CYP2B6, CYP2C8, CYP2D6 and CYP3A4/5
Zell Woodworth, L. Anne Dwyer, Lisa Collins, Terry Graves, Stephanie Helmstetter, Brian Ogilvie, Clayton Otwell, Chad Pope, Tiffin Ramsey, Phyllis Yerino and Andrew Parkinson

Marker substrates for certain CYPs have changed for several reasons, including the need for improved selectivity and sensitivity, reliable substrates for LC/MS/MS analysis, and substrates that provide greater repeatability. The objectives of this study were to compare sample-to-sample variation in cytochrome P450 enzymatic rates between two or more CYP-specific substrates and to determine Michaelis-Menten kinetic constants for these same reactions using a pool of human liver microsomes.

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Spectrophotometric Determination of Terbinafine Hydrochloride in Bulk Drug and Pharmaceutical Formulation
Chaudhari V. P. Kulkarni M. S. Kuchekar B. S. and Chaudharik. P.

A simple, economical accurate and reproducible U.V. spectrophotometric method for the determination of Terbinafine Hydrochloride in both pure and pharmaceutical dosage form has been developed. Terbinafine Hydrochloride shows maximum absorbance at 223 nm with molar absorptivity of 9.378 x 103 lit/mole/cm. Beer’s law was obeyed in the concentration range of 0.6-4.2 ug/ml. The results of analysis were validated statistically and by recovery studies.

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High Throughput High Content Screening using a Multiwavelength Microplate Cytometer
Sarah Payne, Paul Wylie and Wayne Bowen

The Acumen eX3, a multiwavelength microplate cytometer, offers 405, 488 and 633 nm laser excitations in one instrument. This advancement significantly extends the range of fluorescent reagents that can be combined in multicolour, multiplexed assays over a wavelength range for excitation that is similar to that of white light source instrumentation. Thus, it permits seamless transfer of high content assay protocols, developed using CCD-based imaging devices, onto the Acumen eX3 for screening.

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An Ultra-High Throughput Approach to High Content Screening in 1536-Well Format
Yan Wang, Robert L. Davis and Wayne Bowen

The Acumen Explorer combines the object-recognition capabilities of image-based systems with read speeds similar to that of bulk readers. Here, we demonstrate the powerful integration of an Acumen Explorer with the Kalypsys® Integrated Screening System, with capability to screen > 300,000 wells per day of high content data.

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High Throughput Cell Cycle Analysis using Microplate Cytometry
Tristan Cope and Wayne Bowen

To improve screening efficiency, we have developed a cell cycle analysis method that uses an Acumen Explorer fluorescence microplate cytometer to measure the DNA content of propidium iodide stained fixed cells in microplates. We demonstrate that paclitaxel and vinblastine arrested CHO cells in the expected phase of the cell cycle.

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Detecting the FRET Response of the GeneBLAzer® Cell Line D1 CRE-bla CHO-K1 to Agonists and Antagonists using Microplate Cytometry
Christopher Lupton, Randy Hoffman, Paul Wylie and Wayne Bowen

The GeneBLAzer® CHO.K1-D1 cell line (Invitrogen) stably expresses both the ß-lactamase gene downstream of the cAMP response element (CRE) and the dopamine D1 receptor. Stimulation of the cells with dopamine D1 receptor agonists, results in transcriptional activation of the ß-lactamase gene through CRE. A FRET-enabled substrate (CCF4-AM) fluoresces green, in the absence of ß- lactamase reporter activity, and blue when cleaved.

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Communicating Drug Discovery Data Efficiently and Effectively
Jonathan Davies and Andrew Lemon

In this poster, we present IDBS’ ActivityBase™ - a single, integrated framework that brings together biological and chemical information. The software integrates with Oracle®, the industry standard relational database and familiar Microsoft® applications such as Word and Excel. With all discovery data in one system, the communication of information between scientists is simplified - enabling better, faster decisions and the need for IT support to integrate disparate systems is eliminated.

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A new High Content Screening Paradigm: Combination of Image Analysis Software and Microplate Cytometry
Sarah Payne, Paul Wylie, Simon Carter and Wayne Bowen

Researchers are under increasing pressure to perform high content cell-based assays at throughputs compatible with primary screening. Where throughput is not an issue, microscope-based CCD imagers have predominated within the high content field, due to the breadth of biological assays that can be addressed by image analysis techniques. However, they have limited utility for screening due to their low throughput, limited field of view and generation of terabytes of image data.

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Cloe Screen MDR1-MDCK: A Predictive Model of Drug Permeability
David Turner, Boris Pufong, Susan Hinchliffe, Gayle Corkill, Deborah Slamon, Peter Dykstra, Helen Gill, Clive Dilworth and Darwin Cheney

A MDR1-MDCK permeability screen for assessing the membrane permeability properties of early drug discovery compounds has been developed. This study measured the bi-directional transport of compounds with a range of permeabilities across MDR1-MDCK monolayers. Drug concentrations were analysed by LC-MS/MS, from which apparent permeability values in apical-basolateral and basolateral-apical directions and asymmetry index were calculated.

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Scientific News
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Novel Technique for Kidney Research Developed
To better understand how the treatment leads to kidney damage, and possibly prevent it, a team of researchers at Yale School of Medicine developed a new 3D-imaging technique to peer deep into these vital organs.
Microscopic Fish are 3D-Printed to do More Than Swim
Researchers demonstrate a novel method to build microscopic robots with complex shapes and functionalities.
Promising Class of New Cancer Drugs Cause Memory Loss in Mice
New findings from The Rockefeller University suggest that the original version of BET inhibitors causes molecular changes in mouse neurons, and can lead to memory loss in mice that receive it.
A Better Way to Personalize Bladder Cancer Treatments
Researchers at UC Davis, in collaboration with colleagues at Jackson Laboratory, have developed a new way to personalize treatments for aggressive bladder cancer.
Breath of Fresh Air for Asthmatics
Researchers hope to develop a platform that will allow a range of drugs to be delivered by inhalation.
Capturing Cell Growth in 3-D
Spinout’s microfluidics device better models how cancer and other cells interact in the body.
Elastic Patch Releases Drugs in a Stretch
Researchers from have developed a drug delivery technology that consists of an elastic patch that can be applied to the skin and will release drugs whenever the patch is stretched.
New Extra ‘Sticky’ Microgel Could Revolutionise Bladder Cancer Treatment
Researchers have designed a new super-efficient way of delivering an anti-cancer drug which could extend and improve the quality of life for bladder cancer patients - and perhaps save lives.
Liposomes: A Basis for Drugs of the Future
An international group of scientists have recently presented a review of liposomes, microscopic capsules widely used all over the world in the development of new drugs.
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