- Alcoholism and Thiamine Deficiency
- Drug Transport and Resistance Mechanisms
- Biochemical Acid Research Studies
- Cancer, Hypoxia, and Metabolism
- Folate and B Vitamins Research
- Pharmacological Effects and Toxicity Studies
- Neurological and metabolic disorders
- Metabolism and Genetic Disorders
- HIV/AIDS drug development and treatment
- Cancer therapeutics and mechanisms
- Trace Elements in Health
- Lung Cancer Research Studies
- Amino Acid Enzymes and Metabolism
- RNA Interference and Gene Delivery
- Antibiotics Pharmacokinetics and Efficacy
- Protein Interaction Studies and Fluorescence Analysis
- Nanoparticle-Based Drug Delivery
- Pesticide Exposure and Toxicity
- Advanced Polymer Synthesis and Characterization
- Block Copolymer Self-Assembly
- Infectious Encephalopathies and Encephalitis
- Pesticide Residue Analysis and Safety
- Agricultural safety and regulations
- Toxic Organic Pollutants Impact
- Polymer Surface Interaction Studies
University of Georgia
2012-2022
Georgia College & State University
2013-2019
University of Cincinnati Medical Center
2017
Cincinnati Children's Hospital Medical Center
2017
University of Toronto
2006-2012
SciTech Strategies (United States)
2012
DuPont (United States)
2012
Syngenta (United States)
2012
Bayer (Germany)
2012
Valent BioSciences (United States)
2012
Abstract A major concern regarding the chronic administration of antiretroviral drugs is potential for induction drug efflux transporter expression (i.e., P‐glycoprotein, P‐gp) at tissue sites that can significantly affect distribution and treatment efficacy. Previous data have shown inductive effect human immunodeficiency virus protease inhibitors (PIs) mediated through orphan nuclear receptor, steroid xenobiotic receptor (SXR or hPXR). The objectives this study were to investigate...
The resurgence of interest in cancer metabolism has linked alterations the regulation and exploitation metabolic pathways with an anabolic phenotype that increases biomass production for replication new daughter cells. To support increase rate cells, a coordinated supply nutrients, such as glucose micronutrients functioning enzyme cofactors is required. majority co-enzymes are water-soluble vitamins niacin, folic acid, pantothenic pyridoxine, biotin, riboflavin thiamine (Vitamin B1)....
Human intestinal epithelium expresses a number of drug efflux and influx transporters that can restrict and/or facilitate uptake during absorption. Organic anion-transporting polypeptide 2B1 (OATP2B1), multispecific organic anion transporter localized at the brush-border membrane epithelial cells, is known to transport many endogenous substrates (e.g., steroid conjugates) xenobiotics statins). At present, limited information available on mechanism HIV protease inhibitor (PIs) uptake. In this...
Adaptive responses within hypoxic tumor microenvironments require the altered expression of Solute Carrier (SLC) transporters to maintain nutrient uptake in support cellular metabolism and biosynthesis. Using a real time PCR array strategy further characterize changes transporter chronic hypoxia breast cancer cell line model (BT474), we have found 31 fold increase thiamine transporter, SLC19A3. Thus, investigations into transporters, SLC19A2 SLC19A3, role inducible factor-1 alpha (HIF-1α)...
The utilization of surfactants to increase intestinal absorption drugs is a viable strategy that benefits from increases in drug solubilization and the potential for inhibition P-glycoprotein (P-gp) mediated efflux. However, effective concentration range P-gp most defined over narrow range, below critical micelle (CMC), as result significant sequestration drug. Therefore, objectives these studies were assess if association substrates differing hydrophobicity will impact by amphiphilic...
Abstract Purpose: To assess the pharmacokinetics, tumor drug accumulation, and therapeutic activity of Irinophore C, a novel liposomal formulation irinotecan (CPT-11). Experimental Design: The plasma lactone/carboxy levels CPT-11 SN-38 were determined in mice after single i.v. dose (Camptosar), or t1/2, area under curve, Cmax, clearance calculated. Further, also measured tumor-bearing following C treatment. efficacy was compared with that Camptosar five s.c. human xenografts using...
It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which likely due to insufficient levels cofactor for the function thiamine-dependent enzymes. When excess, both pyruvate can increase stabilization hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting trans-activation HIF-1α regulated genes independent low oxygen, termed pseudo-hypoxia. Therefore, dysfunction cellular metabolism accumulation...
Abstract A new method for reversed phase HPLC determination of thiamine and its major in vivo phosphorylation products, monophosphate (TMP) pyrophosphate (TPP), was developed using tetrabutylammonium hydroxide as the ion‐pairing agent. The separation performed on a Phenomenex Kinetex EVO C 18 column with gradient phosphate‐buffered aqueous solution ion‐pair reagent methanol. duty cycle assay 13 min pyrithiamine successfully used internal standard first time measurement protocol. Detection...
We evaluated the potential of an investigational histone methylation reversal agent, 3-deazaneplanocin A (DZNep), in improving chemosensitivity pancreatic cancer to nucleoside analogs (i.e., gemcitabine). DZNep brought delayed but selective cytotoxicity cells without affecting normal human ductal epithelial (HPDE) cells. Co-exposure and gemcitabine induced cytotoxic additivity or synergism both well- poorly-differentiated cell lines by increased apoptosis. In contrast, exerted antagonism...
Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism energy production in the brain. In developed countries, thiamine deficiency (TD) most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation excitotoxicity. These biochemical lesions result apoptotic cell death both neurons astrocytes. Comparable histological injuries patients with hypoxia/ischemia TD have...
The effectiveness and widespread use of pyrethroid insecticides has lead to concerns regarding their safety. Human ingestion these potentially neurotoxic compounds is typically through hand-to-mouth contact or consumption contaminated foods. A substantial proportion ingested pyrethroids are eliminated in feces, suggesting that absorption limited, possibly by the action efflux transporter P-glycoprotein (P-gp). We utilized caco-2 cells as a model system for intestinal enterocytes...
// Hunter C. Jonus 1 , Bradley S. Hanberry 2 Shivani Khatu Jaeah Kim Hendrik Luesch 3 Long H. Dang 4 Michael G. Bartlett and Jason A. Zastre Department of Pharmaceutical Biomedical Sciences, College Pharmacy, University Georgia, Athens, GA, United States America Pediatrics, Emory University, Atlanta, Medicinal Chemistry, Florida, Gainesville, FL, Division Hematology/Oncology, Internal Medicine, Florida Shands Cancer Center, Correspondence to: Zastre, email: jzastre@uga.edu Keywords:...