Chemicals and Drugs Commons^™

Data Sources Regarding The Nonmedical Use Of Pharmaceutical Opioids In The United States, Teresa D. Schmidt, Amanuel Zimam, Alexandra Nielsen, Wayne Wakeland

Complex Systems Faculty Publications and Presentations

Objective—Recent increases in the nonmedical use of pharmaceutical opioids and the adverse outcomes associated with them have stimulated a large amount of research and data collection on this public health problem. Systematic organization of the available data sources is needed to facilitate ongoing research, analysis, and evaluation. This work offers a systematic categorization of data sources regarding the nonmedical use of pharmaceutical opioids in the United States.

Methods—A list of keywords regarding the nonmedical use of pharmaceutical opioids was used to conduct systematic searches in PubMed®. Filtration of search results generated 92 peer-reviewed academic articles, published between January 1995 and …

Top 10 Medicinal Plants And Their Groundbreaking Impact On Modern Medicine, Jordan N. Patterson, Joan Marie Lausier

Senior Honors Projects

This paper describes ten plants that having been groundbreaking drugs in the past century that were all derived from plants. I chose to do my project on this topic because of my family’s history with natural medicine. In 1999 my mother was diagnosed with Bile Duct cancer and the doctors gave her only a couple of weeks to live. The doctors recommended chemotherapy and radiation, but the results seemed negative for the situation. After some extensive research, my parents found St. Georges Medicinal Wellness Center located in the tiny village of Bad Aibling, Germany. This hospital along with offering traditional …

Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha

Theses and Dissertations (ETD)

Roles of cyclic nucleotides and cyclic nucleotide-dependent signaling molecules in regulating several signaling pathways including cell migration have long been known. However, the new and revolutionary concept is that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules regulates cell migration. Multi-drug resistance protein 4 (MRP4), is a member of the large family of ATP binding cassette (ABC) transporter proteins, that localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a pivotal role in the regulation of intracellular cyclic nucleotide dynamics. In our study …

Strengths And Weaknesses Of Hybrid Tpr Technology For Obtaining Structural And Mechanistic Insights Into Tpr Proteins, Shanshan Yu

Theses and Dissertations (ETD)

Tetratricopeptide (TPR) repeats are a 34-residue helix-turn-helix motif that when repeated pack into a superhelical structure. TPR domains are frequently found mediating protein-protein interactions, often through a central groove. One protein complex bearing numerous TPR repeats is the Anaphase Promoting Complex (APC). The anaphase-promoting complex (APC) is a multi-subunit complex, which orchestrates mitotic cell cycles. APC is an E3 ligase in the ubiquitin cascade, and directs the 26S proteosome degradation of cell-cycle regulators. Throughout mitotic progression, proteins that are key regulators of the cell cycle are assembled with polyubiquitin chains by APC.

One domain of the human APC is comprised …

Studies To Characterize Heavy Metal Content And Migration From Recycled Polyethyleneterephthalate, Michael John-Ross Whitt

Master's Theses

Packaging Materials account for 31% of the world’s municipal solid waste. Agencies like the Environmental Protection Agency (EPA) and the Agency for Toxic Substances and Disease Registry (ATSDR) are pushing for the increased use of recycled thermoplastic materials. Polyethylene terephthalate (PET) is a commonly recycled thermoplastic which is used to package ready-to-eat fruits and vegetables. Most recycled polyethylene terephthalate (RPET) packaging materials contain heavy metal catalysts, the most common being antimony. The recent increased use of recycled plastic materials has been suspected as the source of increased human heavy metal exposure. In this study, cadmium, chromium, nickel, lead and antimony …

Tuning Responsiveness Of Polypeptide Based Block Copolymers For Drug Delivery, Ashley J. Johnson

Dissertations

The goal of this dissertation was to tune the pH response and self-assembled morphologies of amphiphilic polypeptide block copolymers for use as drug delivery vehicles. Poly(L-lysine) and poly(L-glutamtic acid) are responsive, ionizable polypeptides that undergo secondary structure transitions, from α-helix to random coil, whereby the change in conformation of the peptide chain results in changes to the global morphology of a self-assembled system. The main focus of this work was to understand how changes in the polymer composition and the local environment can lead to control over the behavior of the overall system. First, the responsive behavior of poly(L-lysine) block …

Low Molecular Weight Glucosamine/L-Lactide Copolymers As Potential Carriers For The Development Of A Sustained Rifampicin Release System: Mycobacterium Smegmatis As A Tuberculosis Model, Jorge Ragusa

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged …

Pupillometry: A Non-Invasive Technique For Pain Assessment In Paediatric Patients., Mark A. Connelly, Jacob T. Brown, Gregory L. Kearns, Rawni A. Anderson, Shawn D. St Peter, Kathleen A. Neville

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Pupillometry has been used to assess pain intensity and response to analgesic medications in adults. The aim of this observational study was to explore proof of concept for the use of this technique in paediatric patients. Changes in pupil parameters before and after opioid exposure also were evaluated.

DESIGN AND SETTING: This was a single-centre, prospective study conducted at an academic paediatric medical centre.

PATIENTS: Children 9-17 years of age undergoing elective surgical correction of pectus excavatum were enrolled into a protocol approved by the human ethical committee (institutional review board).

INTERVENTIONS: Pupil size and reactivity were measured using …

Characteristics Of Unintentional Prescription Drug Poisoning Admissions Clark County, Nevada 2009-2013, Tamara Bruno

UNLV Theses, Dissertations, Professional Papers, and Capstones

Prescription drug abuse has been the fastest growing drug problem in the United States in recent years, and is the second most commonly abused category of illegal and illicit drugs, after marijuana (SAMHSA, 2013; Carnevale, 2011). Reducing the morbidity and mortality associated with prescription drug abuse in challenging because multiple factors contribute to the problem. Prescribing behaviors and the lack of education among providers and pharmacists along with inadequate counseling and

monitoring of patients prescribed pain medication are important factors (Machikanti, 2007; Okie, 2010). Patients' misuse or abuse, diversion or the sharing or sell of pills, and doctor shopping are …

Caepidr: A Computational Approach To Efficient Peptide Influenced Drug Repurposing, Thomas Francis Long

Boise State University Theses and Dissertations

Since the discovery of the molecular basis of disease, numerous studies have reported a correlation between the activity of specific protein receptors the progression of disease. As a result, drug development has become dependent on the study of protein receptor activities. The relative inexpense of computing hardware has made computational methods an important supplementary tool for receptor modeling. This work details an open source software tool that is capable of both efficiently screening large peptide mutant libraries and enabling 3D conformer-based searches over local molecular databases.

A Computational Approach to Efficient Peptide Influenced Drug Repurposing (CAEPIDR) has been developed to …

Nucleoside Reverse Transcriptase Inhibitors Possess Intrinsic Anti-Inflammatory Activity, Benjamin J. Fowler, Bradley D. Gelfand, Younghee Kim, Nagaraj Kerur, Valeria Tarallo, Yoshio Hirano, Shoba Amarnath, Daniel H. Fowler, Marta Radwan, Mark T. Young, Keir Pittman, Paul Kubes, Hitesh Agarwal, Keykavous Parang, David R. Hinton, Ana Bastos-Carvalho, Shengjian Li, Testuhiro Yasuma, Takeshi Mizutani, Reo Yasuma, Charles Wright, Jayakrishna Ambati

Pharmacy Faculty Articles and Research

Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)–derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile …

Crystal Structures Of 2-Meth­Oxy­Isoindoline-1,3-Dione, 1,3-Dioxoisoindolin-2-Yl Methyl Carbonate And 1,3-Dioxo-2,3-Di­Hydro-1h-Benzo[De]Isoquinolin-2-Yl Methyl Carbonate: Three Anti­Convulsant Compounds, Fortune Ezemobi, Henry North, Kenneth R. Scott, Anthohy K. Wutoh, Ray J. Butcher

Faculty Research ​and Publications

The title compounds, C9H7NO3, (1), C10H7NO5, (2), and C14H9NO5, (3), are three potentially anti­convulsant compounds. Compounds (1) and (2) are isoindoline derivatives and (3) is an iso­quinoline derivative. Compounds (2) and (3) crystallize with two independent mol­ecules (A and B) in their asymmetric units. In all three cases, the isoindoline and benzoiso­quinoline moieties are planar [r.m.s. deviations are 0.021 Å for (1), 0.04 and 0.018 Å for (2), and 0.033 and 0.041 Å for (3)]. The substituents attached to the N atom are almost perpendicular to the mean planes of the heterocycles, with dihedral angles of 89.7 (3)° …

Peptide Arrays For Detecting Naphthenic Acids In Oil Sands Process Affected Water, Kamaljit Kaur, Subir Bhattacharjee, Rajesh G. Pillai, Sahar Ahmed, Sarfuddin Azmi

Pharmacy Faculty Articles and Research

Naphthenic acids (NAs) are water-soluble components of petroleum. The characterization and quantification of NAs by analytical methods have proved quite challenging, whilst the toxic effects of these water-soluble compounds on a variety of organisms adversely affecting reproduction and steroid production is becoming apparent. In this study, we report a fluorescence-based competitive binding method for rapid sensing of the presence of NAs using cellulosic peptide array strips as sensors. The peptide array was designed from sequences derived from the estrogen receptor (ER). Several of these peptides were able to detect the presence of NAs at low micromolar (∼5 mg L^{−1 …}

The Translational Biology Of Remyelination: Past, Present, And Future, Robin J.M. Franklin, Vittorio Gallo

Pediatrics Faculty Publications

Amongst neurological diseases, multiple sclerosis (MS) presents an attractive target for regenerative medicine. This is because the primary pathology, the loss of myelin-forming oligodendrocytes, can be followed by a spontaneous and efficient regenerative process called remyelination. While cell transplantation approaches have been explored as a means of replacing lost oligodendrocytes, more recently therapeutic approaches that target the endogenous regenerative process have been favored. This is in large part due to our increasing understanding of (1) the cell types within the adult brain that are able to generate new oligodendrocytes, (2) the mechanisms and pathways by which this achieved, and (3) …

Hydroxamic Acid-Based Histone Deacetylase (Hdac) Inhibitors Can Mediate Neuroprotection Independent Of Hdac Inhibition, Sama Sleiman, Yan-Ling Zhang, Jennifer Gale, Manuela Basso, Giovanni Coppola, John T. Pinto, Rajiv Ratan

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibition improves function and extends survival in rodent models of a host of neurological conditions, including stroke, and neurodegenerative diseases. Our understanding, however, of the contribution of individual HDAC isoforms to neuronal death is limited. In this study, we used selective chemical probes to assess the individual roles of the Class I HDAC isoforms in protecting Mus musculus primary cortical neurons from oxidative death. We demonstrated that the selective HDAC8 inhibitor PCI-34051 is a potent neuroprotective agent; and by taking advantage of both pharmacological and genetic tools, we established that HDAC8 is not critically involved in PCI-34051's …

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …

Targeting The Small- And Intermediate Conductance Ca2+- Activated Potassium Channels: The Drug Binding Pocket At The Channel/Calmodulin Interface, Meng Cui, Guangrong Qin, Kunqian Yu, M. Scott Bowers, Miao Zhang

Pharmacy Faculty Articles and Research

The small- and intermediate-conductance Ca 2+ -activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca 2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca 2+ -binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been …

Hepatic Carboxylesterase 1 Is Induced By Glucose And Regulates Postprandial Glucose Levels, Jiesi Xu, Liya Yin, Yang Xu, Yuanyuan Li, Munaf Zalzala, Gang Cheng, Yanqiao Zhang

Chemical, Biomolecular, and Corrosion Engineering Faculty Research

Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1) is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, …

The Non-Canonical Hydroxylase Structure Of Yfcm Reveals A Metal Ion-Coordination Motif Required For Ef-P Hydroxylation, Kan Kobayashi, Assaf Katz, Andrei Rajkovic, Ryohei Ishii, Owen E. Branson, Michael A. Freitas, Ryuichiro Ishitani, Michael Ibba, Osamu Nureki

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

EF-P is a bacterial tRNA-mimic protein, which accelerates the ribosome-catalyzed polymerization of poly-prolines. In Escherichia coli, EF-P is post-translationally modified on a conserved lysine residue. The post-translational modification is performed in a two-step reaction involving the addition of a β-lysine moiety and the subsequent hydroxylation, catalyzed by PoxA and YfcM, respectively. The β-lysine moiety was previously shown to enhance the rate of poly-proline synthesis, but the role of the hydroxylation is poorly understood. We solved the crystal structure of YfcM and performed functional analyses to determine the hydroxylation mechanism. In addition, YfcM appears to be structurally distinct from any …

Treating Cocaine Dependency With Psychopharmacotherapy And Behavioral Therapy, Robyn Liebman

e-Research: A Journal of Undergraduate Work

Cocaine is an addictive drug that affects more than 14 million people globally, according to the United Nations. This paper is a conceptual meta-analysis of numerous studies that tested the effects of psychopharmacological therapy along with behavioral therapy in the treatment of cocaine addiction. It is hypothesized that cocaine dependent individuals treated with a combination of psychopharmacological and behavioral therapies will be less likely to use cocaine. Measurements of cocaine use throughout the experiments were generally assessed by urine screenings. Results indicate that there is more evidence that a combination of psychopharmacological and behavioral therapies will reduce cocaine use. There …