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Wednesday, January 28, 2015
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A Robust High Throughput Physicochemical Screen for Phospholipidosis
Pavol Vitovic, Juha-Matti Alakoskela and Paavo K.J. Kinnunen

The poster presents a simple HT physicochemical screen, predicting PLD in real-time by surface activity profiling (using Kibron Delta-8 analyzer). The results are equal or better than derived from a cell based assay, throughput is up 450 compounds/24 hrs and drug consumption < 1 mg/compound.

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Promega’s Multiplexed Cell Viability and Apoptosis Assays Performed on the PHERAstar
Tracy Worzella and Brad Larson

Today’s high-throughput screening facilities face increasing demands to generate more information from their existing compound libraries. In this poster, we demonstrate the combination of several Promega cell-based assays (CellTiter-Blue®, Apo-One® and Caspase-Glo® 3/7) multiplexed in both low-volume 384 and 1536-well plate formats. The BMG LABTECH PHERAstar microplate reader is used to record both luminescence and fluorescence, depending on the multiplex combination.

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Promega’s Multiplexed Luciferase Reporter and Cell Viability Assays performed on the PHERAstar
Tracy Worzella and Brad Larson

By multiplexing a reporter assay (EnduRen™, ViviRen™) with a cell viability assay (CellTiter-Glo®), it is possible to determine if reporter response variations are due to changes in cell number and health. In this poster, we demonstrate the combination of several Promega cell-based assays multiplexed in both low-volume 384- and 1536-well plate formats using the BMG LABTECH PHERAstar microplate reader to record luminescence.

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Metabolic Stability and Clearance of Pharmaceutical Chemicals in Pre-Pooled Cryopreserved Hepatocytes
Aruna Koganti, Nicola J. Hewitt, Wei Zhang, Michael Cheseborough, Christopher M. Terrell, Paul M. Silber and Charles B. Jensen

Cryopreserved hepatocytes express both phase I and phase II enzymes and facilitate early evaluation of the metabolic stability of pharmaceuticals. Availability of pre-pooled cryopreserved hepatocytes further enhances the utility of this model by reducing donor to donor variability. In this study, the metabolic stability of 29 pharmaceutical compounds were evaluated in pre-pooled cryopreserved human hepatocytes.

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CYP4F Enzymes are the Major Enzymes in Human Liver Microsomes that Catalyze the O-Demethylation of the Antiparasitic Prodrug DB289
Greg Loewen, Michael Zhuo Wang, Janelle Saulter, Etsuko Usuki, Yen-Ling Cheung, Michael Hall, Arlene Bridges, Oliver Parkinson, Chad Stephens, James Allen, Darryl Zeldin, David Boykin, Richard Tidwell, Mary Paine, James Hall and Andrew Parkinson

DB289 is a prodrug that is converted by several steps to the active metabolite DB75. DB289 exhibits enhanced oral efficacy and reduced acute toxicity over DB75, an aromatic dicationic compound that is effective against a broad range of pathogens in vitro including African trypanosomiasis (African sleeping sickness). This reaction phenotyping study aimed to identify the enzymes responsible for oxidative O-demethylation; the first step in this conversion to DB75.

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Effects of Gender, age and Ethnicity on Human Cytochrome P450 Activity
Lisa Collins, L. Anne Dwyer, Zell Woodworth, Tiffin Ramsey, Clayton Otwell, Chad Pope, Stephanie Helmstetter, Terry Graves, Josh Snyder, Jason Barricklow and Andrew Parkinson

The expression of CYP enzymes is influenced by both endogenous and exogenous factors. The aim of this analysis was to evaluate whether the age, gender, or ethnicity of the donor should influence the selection of human liver microsomes for drug metabolism studies, as well as whether cigarette smoking and alcohol consumption are reliable indicators of elevated CYP1A2 and CYP2E1 activity, respectively.

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Alfentanil N-deakylation: Monitoring the Formation of N-phenylpropionamide (AMX) to Determine CYP3A4 Activity in Vitro
Phyllis Yerino, Paul Toren and Andrew Parkinson

Alfentanil is a synthetic analgesic cleared exclusively by hepatic metabolism. Due to the highly linear correlation between alfentanil systemic clearance and CYP3A4 activity, as well as the direct pharmacologic effects on pupil size, it has been used as a non-invasive metabolic probe for CYP3A4 activity in vivo. AMX is a direct metabolite of alfentanil, evaluated in this study for its potential to measure CYP3A4 activity in vitro.

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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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Showing Results 81 - 90 of 121
Scientific News
First Contracting Human Muscle Grown in Laboratory
Researchers at Duke University report the first lab-grown, contracting human muscle, which could revolutionize drug discovery and personalized medicine.
Antriabio Announces Completion Of PK/PD Studies Of AB101
AB101 positioned to be the first once-weekly basal insulin for diabetes patients.
Anti-Diabetic Drug Springs New Hope for Tuberculosis Patients
Drug for treating diabetes can double up as adjunct treatment for tuberculosis.
A Poisonous Cure
Toxic fungi may hold the secrets to tackling deadly diseases.
Antibiotic Resistance Threatens Future of Modern Medicine
Overuse and misuse of antibiotics, one of the key contributors to antimicrobial resistance (AMR).
Bacterial Toxin Targets Discovered
Understanding how bacterial toxins target human cells is set to have major implications for the development of novel drugs.
Proteomics for Systems Toxicology
MS-based proteomics is maturing into a robust technology for the measurement of proteome-wide exposure effects.
Molecular Event Mapping Opens Door to more in silico Tests
It is hoped that this new approach to mapping and predicting the impact of chemical compounds in the body could reduce the need for toxicity tests in animals.
Protein-engineered Cages Aid Studies of Cell Functions
The Cages, from researchers at Tokyo Institute of Technology, to deliver an important signalling molecule, carbon monoxide, into cells.
Wallet-Sized Labs The Next Big Thing
RMIT researchers are developing inexpensive, portable toxicology laboratories so small you could fit them in your wallet.
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