|A Systematic Review of Lifestyle Modification in Adults with Non-Alcoholic Fatty Liver Disease|
C. Thoma, C. P. Day and M. I. Trenell, Newcastle University
This study reviews the causes of non-alcoholic fatty liver disease and the associated risk factor for type 2 diabetes and cardiovascular disease.
|Cytotoxicity Screen of Mangiferin and its Major Metabolite Norathyriol in Human Tumor Cell Lines|
Souza, J.R.R., Feitosa, J.P.A., Ricardo, N.M.P.S, Trevisan, M.T.S., Frei, E., Ulrich C.M., Owen, R.W.
Many natural products are available worldwide as potential chemoprotective agents against commonly occurring cancers, for example Mangiferin which has low bioavailability and is thought to be mainly available in the colon.
|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.
|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.
|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.
|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.
|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.
|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.
|Live Cell Beating Assay Using Human iPSC-derived Cardiomyocytes for Evaluation of Drug Efficacy and Toxicity|
Oksana Sirenko, Carole Crittenden, Blake Anson, Jayne Hesley, Yen-Wen Chen, Nick Callamaras and Evan F. Cromwell
A large percentage of new drugs fail in clinical studies due to cardiac toxicity. Development of highly predictive in vitro assays suitable for screening, safety assessment or other environments is therefore extremely important for drug development. Human cardiomyocytes derived from stem cell sources can greatly accelerate the discovery of cardiac drugs and improve drug safety by offering more clinically relevant cell-based models than those presently available.