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ASSESSMENT OF A MICROPATTERNED HEPATOCYTE CO-CULTURE SYSTEM TO DETECT COMPOUNDS THAT CAUSE DRUG INDUCED LIVER INJURY IN HUMANS
Salman Khetani, Chitra Kanchagar, Stacy Krzyzewski, Michael D. Aleo and Yvonne Will

This case study demonstrates the increased success of Hepregen’s novel micro-patterned co-culture system in identifying primary and secondary circulating and excretory metabolites when compared to liver microsomes, S-9 fractions and primary human hepatocyte suspensions for a series of 27 compounds with known in vivo human metabolite profiles.

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Nanoliter Volume Pin Tool Transfers as Measured by a Dual-Dye Absorbance Method
Duong T. Chau; Patrick H. Cleveland, Ph.D.; John Thomas Bradshaw, Ph.D.

Increasing costs of chemical compounds and commonly used solvents has pushed high throughput screening labs towards lower working volumes, specifically in the nanoliter range. The ability to controllably dispense “known” nanoliter aliquots of samples is desired, which can readily be achieved using Pin Tools.

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Why Is My Assay Failing? An Approach to Assay Equipment Optimization
Tanya R. Knaide, John Thomas Bradshaw, Kevin Khovananth, Keith Albert

Assays can produce unexpected or failing results for a multitude of reasons. Variability may be introduced at any point within the assay process.

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Validation of an Automated Cell-Based Bioluminescent TNFa Blocker Bioassay
Brad Larson, Tracy Worzella, Rich Moravec, Neal Cosby, Frank Fan, Teresa Surowy and Peter Banks

TNFa blocker biopharmaceuticals represent an important and successful class of protein drugs used in the treatment of several autoimmune diseases. Bioassays are indispensible tools in biopharmaceutical drug development and commercialization that are used to quantify biological activity and stability of drugs or drug candidates. The automation of these assays can serve to create an accurate, robust process which can allow the researcher to perform other more important functions.

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Modeling Disposition of Sotalol following Intravenous and Oral Administration in Healthy Adult Subjects
S. Ray Chaudhuri, V. Lukacova and W. S. Woltosz

Sotalol is a non specific adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmia. Its absorption, distribution and systemic PK or, collectively, ‘disposition’ was modeled and simulated using GastroPlus™ v7.0. Biopharmaceutical properties were obtained from in silico predictions and in vitro measurements.

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Predicting hERG Potassium Channel Affinity with Artificial Neural Network Ensembles
Adam C. Lee, GrazynaFraczkiewicz, Robert Fraczkiewicz, Robert D. Clark and Walter S. Woltosz

Modeling hERG inhibition has gained significant popularity since 2005, when the FDA recognized the correlation between hERG inhibition and a prolonged QT interval by issuing guidance for the evaluation of new non-antiarrythmic drugs against the hERG channel.Long QT syndrome or LQTS is a risk factor for ventricular tachyarrhythmias and sudden death.

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Predicting Sites of Metabolism with Artificial Neural Network Ensembles
Marvin Waldman, Robert Fraczkiewicz, JinhuaZhang, Robert D. Clark and Walter S. Woltosz

Hepatic first-pass metabolism of many drugs and pro drugs plays a key role in their oral bioavailability. The human cytochrome P450 enzymes are responsible for the metabolism of most drugs. Knowledge of likely sites of metabolic attack in a drug molecule can aid in designing out unwanted metabolic liabilities early on in the drug discovery process, as well as in the design of pro drugs where metabolic transformation is desired.

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Be Careful What You Ask for: Challenges of Predicting Human Clearance for a Low Metabolic Turnover Compound, ELND006
Kevin Quinn, David Nakamura, Heather Zhang, Shawn Gauby, Colin Lorentzen, Erich Goldbach, Amanda Moore, Salman Khetani, Earvin Liang, John-Michael Sauer and George Tonn,

A study of in vitro clearance of ELND006, a low turn-over compound.

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Global Gene Expression Changes Induced In Primary Human Hepatocytes By Thiazolidinediones Upon Repeat Dosing of HepatoPac™ Cultures
Michael McVay and Salman R. Khetani

An assessment of global gene expression changes in HepatoPac, a micropatterned co-culture of hepatocytes and stromal cells.

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Scientific News
Adipose Tissue Secretes Factors That Activate Metabolism
Study finds brown adipose tissue secretes signalling factors that activates metabolism of fat and carbohydrates.
Insight into Eye Diseases
Scientists recreate zebrafish cell regeneration from retinal stem cells in mice.
Developing Novel Ear Infection Treatments
Research team engineers antibiotic gel for treating middle ear infections.
Iron Nanoparticles Make Immune Cells Attack Cancer
Researchers accidentally discover that nanoparticles invented for anemia treatment can trigger the immune system’s ability to destroy tumor cells.
Stem Cell ‘Heart Patch’ Almost Perfected
Scientists aiming to perfect and test 3D "heart patches" in animal model, last hurdle before human patients.
Fighting Cancer with Sticky Nanoparticles
Treatment that uses bioadhesive nanoparticles drug carriers proved more effective than conventional treatments for certain cancers.
Smart Material Hunts Cancers
Team has created smart material that locates and images cancer or tumour sites in tissue.
Targeting Fat to Treat Cancer
Researchers develop novel cancer treatment that halts fat synthesis in cells, stunting tumors.
Reprogramming Lymph Nodes to Fight MS
Bioengineers work to reprogram lymph node function to fight multiple sclerosis.
Arms Race with a Superbug
Scientists have discovered that increased risk of superbug infection can be directly casued by immune system response to invading bacteria.
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