Chemical and Pharmacologic Phenomena Commons^™

Weaponizing Tear Gas: Bahrain’S Unprecedented Use Of Toxic Chemical Agents Against Civilians., Richard Sollom, Holly G. Atkinson

Publications and Research

The Bahraini government’s response to the early 2011 pro-democracy protests was brutal, systematic, and violent. In addition to birdshot and rubber bullets, government law enforcement attacked unarmed protestors with toxic chemical agents including tear gas. The government’s crackdown on the medical profession was especially harmful, as security forces arrested and detained doctors, raided health facilities, and obstructed patients from receiving necessary care. This report’s findings are based on field research that the authors conducted in Bahrain (April 2012) to investigate excessive use of force by law enforcement officials since June 2011—the end of Bahrain’s state of emergency. The medico-legal team …

Reactions Of Methyl Perfluoroalkyl Ethers With Isopropyl Alcohol: Experimental And Theoretical Studies, Howard Knachel, Vladimir Benin, Chadwick Barklay, Janine C. Birkbeck, Billy D. Faubion, William E. Moddeman

Chemistry Faculty Publications

The reaction of an isomeric mixture of the methyl perfluoroalkyl ether, C4F9OCH3 (Novec-7100), in the presence of isopropyl alcohol (IPA) and/or water has been studied by measuring the rate of product formation using an ion-selective electrode (ISE) for fluoride ion, Karl Fisher coulometric titrations for water, and 1H and 19F NMR spectroscopy for product identification and rate studies. The results showed the methyl perfluoroalkyl ether to be very stable with products forming at the rate of ∼1 ppm per year at a laboratory temperature of 20 °C. Measurements over the temperature range of 6° to 100 °C were made on …

The Susceptibility Of Trypanosomatid Pathogens To Pi3/Mtor Kinase Inhibitors Affords A New Opportunity For Drug Repurposing, Rosario Diaz-Gonzalez, F. Kuhlmann, Cristina Galan-Rodriguez, Luciana Madeira Da Silva, Caitlin Karver, Ana Rodriguez, Stephen Beverley, Miguel Navarro, Michael Pollastri

Michael Pollastri

Background Target repurposing utilizes knowledge of "druggable" targets obtained in one organism and exploits this information to pursue new potential drug targets in other organisms. Here we describe such studies to evaluate whether inhibitors targeting the kinase domain of the mammalian Target of Rapamycin (mTOR) and human phosphoinositide-3-kinases (PI3Ks) show promise against the kinetoplastid parasites Trypanosoma brucei, T. cruzi, Leishmania major, and L. donovani. The genomes of trypanosomatids encode at least 12 proteins belonging to the PI3K protein superfamily, some of which are unique to parasites. Moreover, the shared PI3Ks differ greatly in sequence from those of the human host, …

Synthetic Peptides Derived From The Sequence Of A Lasso Peptide Microcin J25 Show Antibacterial Activity, Rania Soudy, Liru Wang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Microcin J25 (MccJ25) is a plasmid-encoded, ribosomally synthesized antibacterial peptide with a unique lasso structure. The lasso structure, produced with the aid of two processing enzymes, provides exceptional stability to MccJ25. We report the synthesis of six peptides (1–6), derived from the MccJ25 sequence, that are designed to form folded conformation by disulfide bond formation and electrostatic or hydrophobic interactions. Two peptides (1 and 6) display good activity against Salmonella newport, and are the first synthetic derivatives of MccJ25 that are bactericidal. Peptide 1 displays potent activity against several Salmonella strains including two …

Modified-Release Drugs, Chedva Farkas

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt from the introduction to this article: Ever since the discovery of bacteria and their role in the disease process in the mid-1800s, scientists have been heavily involved in the discovery and development of drug therapies and their mechanism of action in the human body. Shortly after the initial discovery came the era of drug discovery of the late 1800s-early 1900s, also known as the “drug revolution” (Dash and Cudworth 1998). Although the drug revolution led to the rapid discovery of many new drugs, pharmacological factors such as dosage forms, drug delivery systems, plasma drug levels, …

Effects Of Combined Opioids On Pain And Mood In Mammals, David J. Mokler, Richard H. Rech, Shannon L. Briggs

Biomedical Sciences Faculty Publications

The authors review the opioid literature for evidence of increased analgesia and reduced adverse side effects by combining opioid-receptor (MOR) agonists, kappa-opioid-recepter (KOR) agonists, and nonselective low-dose-opioid antagonists (LD-ANT). We tested fentanyl (MOR agonist) and spiradoline (KOR agonist), singly and combined, against somatic and visceral pain models. Combined agonists induced additive analgesia in somatic pain and synergistic analgesia in visceral pain. Other investigators report similar effects and reduced tolerance and dependence with combined MOR agonist and KOR agonist. LD-Ant added to either a MOR agonist or KOR agonist markedly enhanced analgesia of either agonist. In accordance with other place-condition (PC) …

Synthesis And Flame Retardant Testing Of New Boronated And Phosphonated Aromatic Compounds, Vladimir Benin, Sravanthi Durganala, Alexander Morgan

Chemistry Faculty Publications

The present report describes the preparation and use of some dimethyl terephthalate derivatives in transition metal-catalyzed coupling reactions to produce new reactive flame retardants. Dimethyl iodoterephthalate and dimethyl 2,5-diiodoterephthalate were successfully employed in the preparation of phosphonic and boronic esters and acids. The latter were tested for heat release with a microcombustion calorimeter (ASTM D7309) to determine the potential for heat release reduction of these flame retardant molecules. The results showed that the addition of boronic or phosphonic acids greatly lowered the heat release, due to a condensed phase (char formation) mechanism. Adding ester groups to the boronic acids or …

The Tetrafluoroborate Salt Of 4-Methoxybenzyl N-2-(Dimethylamino)Ethyl-N-Nitrosocarbamate: Synthesis, Crystal Structure And Dft Calculations, Helene Hedian, Vladimir Benin

Chemistry Faculty Publications

The tetrafluoroborate salt of 4-methoxybenzyl N-2-(dimethylamino)ethyl-N-nitrosocarbamate was prepared in two steps, via the corresponding carbamate. Its crystal structure is monoclinic, space group P21/c. The unit cell dimensions are: a = 19.499(8) Å, b = 5.877(3) Å, c = 15.757(7) Å, α = 90°, β = 110.019(7)°, γ = 90°, V = 1696.5(12) Å3, Z = 4. The structure exhibits an unexpected, pseudo-gauche conformation with respect to the C2–C3 bond, due to a stabilizing hydrogen bond between the carbonyl oxygen (O1) and the hydrogen atom at the trialkylammonium center (H3n), with a distance between them of …

Modelling Β2ar Regulation, Sharat J. Vayttaden

Dissertations & Theses (Open Access)

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models …

Substrate Envelope And Drug Resistance: Crystal Structure Of Ro1 In Complex With Wild-Type Human Immunodeficiency Virus Type 1 Protease, Moses Prabu-Jeyabalan, Nancy M. King, Ellen A. Nalivaika, Gabrielle Heilek-Snyder, Nick Cammack, Celia A. Schiffer

Celia A. Schiffer

In our previous crystallographic studies of human immunodeficiency virus type 1 (HIV-1) protease-substrate complexes, we described a conserved "envelope" that appears to be important for substrate recognition and the selection of drug-resistant mutations. In this study, the complex of HIV-1 protease with the inhibitor RO1 was determined and comparison with the substrate envelope provides a rationale for mutational patterns.

Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Background: Cerium oxide (CeO₂) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO₂ nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats.

Methods and results: Compared with control animals, CeO₂ nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO₂nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO₂ nanoparticles.

Conclusion: Taken together, these data suggest that intratracheal instillation …

Application Of Raman Spectroscopy To Lubricants, Lubricated Surfaces And Lubrication Phenomena, David W. Johnson

Chemistry Faculty Publications

Recent advances in lasers and detector technologies and the development of low-cost instruments and fiber-optic probes have brought about an explosion in the lubrication systems being studied by Raman spectroscopy. This article provides examples of the use of Raman spectroscopy in the study of lubrication phenomena, including the characterization of liquid lubricants, lubricant additives, and solid lubricants; the study of vapor-phase lubrication; and the use of coated nanoparticles as lubricants.

A Sodium Salt Of The Dimer Of Boronoterephthalic Acid Anhydride, Scott Simmons, Albert Fratini, Vladimir Benin

Chemistry Faculty Publications

The title compound, sodium bis­(6-carb­oxy-1-hy­droxy-3-oxo-1,3-dihydro-2,1-benzoxaborol-1-yl)oxidanium, Na+·C16H15B2O13-, was prepared in two steps from 2-bromo-p-xylene. Its crystal structure was determined at 140 K and has triclinic (P) symmetry. The compound presents a unique structural motif, including two units of the cyclic anhydride of boronoterephthalic acid, joined by a protonated, and thereby trivalent, oxonium center. Association in the crystal is realized by complementary hydrogen bonding of the carboxyl groups, as well as by coordination of the sodium cations to the oxygen centers on the five-membered rings.

Theoretical Investigation Of A Reported Antibiotic From The 'Miracle Tree' Moringa Oleifera, Michael Horwath, Vladimir Benin

Chemistry Faculty Publications

Moringa oleifera, sometimes called the “Miracle Tree,” has received international attention for its potential to improve health in impoverished tropical areas. In addition to high vitamin content in the leaves and pods, the tree contains compounds with antioxidant and antibacterial properties. This study focused on the theoretical investigation of the suggested structure of one antibacterial compound, “pterygospermin,” whose existence was proposed after some studies of the roots of M. oleifera. The structure of pterygospermin was first proposed by a research group working in the 1950s, but later studies have not found evidence of this compound and have instead …

Exhausted Or Unlicensed: Can Field-Of-Use Restrictions In Biotech License Agreements Still Prevent Off-Label Use Promotion After Quanta Computer?, Kristal M. Wicks

The University of New Hampshire Law Review

[Excerpt] “In the biotechnology (biotech) industry, companies must be increasingly aware of their intellectual property and how their licensing strategies can impact their rights. When licensing patented technology, it is common practice for biotech companies to include restricted field-of-use provisions in their license agreements. Such provisions permit a licensee to only use licensed technology in a defined field and restrict use or development in another field. This licensing strategy plays an important role within the biotech industry because it allows companies to more effectively control their intellectual property and to more efficiently research and develop pharmaceutical products.

A problem that …

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …

Pk/Pd Modelling Of Comb-Shaped Pegylated Salmon Calcitonin Conjugates Of Differing Molecular Weights, Sinead Ryan, Jesus Maria Frias, David H. Haddleton, David J. Brayden

Articles

Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel combed-shaped end-functionalised poly(PEG) methyl ether methacrylate) (sCT-P) comb-shaped polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40 kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E …