Medicine and Health Sciences Commons^™

Discovery Of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening, Diana Ortiz, W. Armand Guiguemde, Jared T. Hammill, Angela K. Carrillo, Yizhe Chen, Michele Connelly, Kayla Stalheim, Carolyn Elya, Alex Johnson, Jaeki Min, Anang Shelat, David C. Smithson, Lei Yang, Fangyi Zhu, R. Kiplin Guy, Scott M. Landfear

Pharmaceutical Sciences Faculty Publications

Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic acid …

Type 2 Neural Progenitor Cell Activation Drives Reactive Neurogenesis After Binge-Like Alcohol Exposure In Adolescent Male Rats, Chelsea Rhea Geil Nickell, Hui Peng, Dayna M. Hayes, Kevin Y. Chen, Justin A. Mcclain, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Excessive alcohol consumption during adolescence remains a significant health concern as alcohol drinking during adolescence increases the likelihood of an alcohol use disorder in adulthood by fourfold. Binge drinking in adolescence is a particular problem as binge-pattern consumption is the biggest predictor of neurodegeneration from alcohol and adolescents are particularly susceptible to the damaging effects of alcohol. The adolescent hippocampus, in particular, is highly susceptible to alcohol-induced structural and functional effects, including volume and neuron loss. However, hippocampal structure and function may recover with abstinence and, like in adults, a reactive burst in hippocampal neurogenesis in abstinence may contribute to …

Development Of Halofluorochromic Polymer Nanoassemblies For The Potential Detection Of Liver Metastatic Colorectal Cancer Tumors Using Experimental And Computational Approaches, Derek Alexander Reichel, Louis T. Curtis, Elizabeth Ehlman, B. Mark Evers, Piotr G. Rychahou, Hermann B. Frieboes, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Purpose—To develop polymer nanoassemblies (PNAs) modified with halofluorochromic dyes to allow for the detection of liver metastatic colorectal cancer (CRC) to improve therapeutic outcomes.

Methods—We combine experimental and computational approaches to evaluate macroscopic and microscopic PNA distributions in patient-derived xenograft primary and orthotropic liver metastatic CRC tumors. Halofluorochromic and non-halofluorochromic PNAs (hfPNAs and n-hfPNAs) were prepared from poly(ethylene glycol), fluorescent dyes (Nile blue, Alexa546, and IR820), and hydrophobic groups (palmitate), all of which were covalently tethered to a cationic polymer scaffold [poly(ethylene imine) or poly(lysine)] forming particles with an average diameter < 30 nm.

Results—Dye-conjugated PNAs showed no aggregation under …

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers, Fei Tang, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against …

Toxic And Essential Trace Element Content Of Commonly Administered Pediatric Oral Medications, Robert A. Yokel, Sarah E. Seger, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

OBJECTIVES: The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications.

METHODS: Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication's maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral …