Chemicals and Drugs Commons^™

The Molecular Basis Of Fitness And Transmissibility Of Neuraminidase Inhibitor Resistant Influenza A Viruses, Susu Duan

Theses and Dissertations (ETD)

Neuraminidase (NA) inhibitors including oral oseltamivir and inhaled zanamivir are among the first line of defense against influenza virus infection. Development of resistance to NA inhibitors is a huge drawback for limited options for the control of influenza. During the first decade of NA inhibitor use, the detection rates of resistance to both NA inhibitors had remained low in circulating influenza viruses. However, the 2008~2009 season was marked by a radical increase of prevalence of oseltamvir resistance from <1% to >90% in worldwide surveillance in less than a year. The resistance was solely linked to NA H275Y variants of seasonal H1N1 viruses, …

Arsenic Contamination In Groundwater In Vietnam: An Overview And Analysis Of The Historical, Cultural, Economic, And Political Parameters In The Success Of Various Mitigation Options, Thuy M. Ly

Pomona Senior Theses

Although arsenic is naturally present in the environment, 99% of human exposure to arsenic is through ingestion. Throughout history, arsenic is known as “the king of poisons”; it is mutagenic, carcinogenic, and teratogenic. Even in smaller concentrations, it accumulates in the body and takes decades before any physical symptoms of arsenic poisoning shows. According to the World Health Organization (WHO), the safe concentration of arsenic in drinking water is 10 µg/L. However, this limit is often times ignored until it is decades too late and people begin showing symptoms of having been poisoned.

This is the current situation for Vietnam, …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations and Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

Pharmacokinetic/Pharmacodynamic (Pk/Pd) Modeling Of Anti-Neoplastic Agents, Daniel Lexcen, Ahmed H. Salem, Walid F. Elkhatib, Virginia Haynes, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Development of tumor resistance to chemotherapeutics is related to inherent tumor variations regarding sensitivity to chemotherapeutics and to sub-optimal dosing regimens, including variation in patient pharmacokinetics that result in suboptimal exposure of tumor cells to anti-neoplastic drugs [1, 2]. The rate and extent of drug efficacy depends on the extent of drug exposure at the tumor site and the time above the effective concentration [3]. In vitro models that incorporate these pharmacokinetic and pharmacodynamic (PK/PD) principles to optimize therapeutic response may be considered the method of choice for optimizing dosing schedules before translating data from static assays to animals and …

Application Of Pharmacokinetics/Pharmacodynamics (Pk/Pd) In Designing Effective Antibiotic Treatment Regimens, Ghada F. Ahmed, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Designing antibiotic dosing regimens is often not optimal and the dose-response relationship for most antibiotics is not well-known1. Both Pharmacokinetics (PK) and Pharmacodynamics (PD) are characteristics of antimicrobial agents that should be considered in the development of effective antibiotic therapy. By linking the concentration time profile at the site of action to the drug effect (PK/PD), the effect of varying dosage regimens against pathogens could be simulated enabling the identification of effective dosage strategies. It is known that inadequate antibiotic dosing could not only lead to a therapeutic failure, but also to the development of bacterial resistance. Importantly, the evolution …

Water Pipe Smoking Amongst The University And College Students Of Karachi, Pakistan, Shehla Batool Jaffri, Aisha Yousuf, Waris Qidwai

Department of Family Medicine

Background:

An extensive literature search revealed that water pipe smoking is an emerging health risk and deserves the attention of health professionals. This study was therefore undertaken to determine the frequency of water pipe smoking among students in college and universities of Pakistan and to assess the practices, knowledge and attitude towards water pipe smoking among them.

Method:

A cross sectional survey was conducted in the College and Universities of Karachi, Pakistan from April 2009 to October 2009. Students were selected through non probability sampling and given self administered questionnaire after the informed consent.

Result:

A total …

Facing An Epidemic: An Analysis Of Hiv/Aids, Antiretroviral Drug, And International Response To The Aids Pandemic, Michael Tate

Annual Undergraduate Conference on Health and Society

More than 33 million people are living with HIV/AIDS around the globe with 68% of all cases occurring in sub-Saharan Africa. The global prevalence rate is shocking considering that the disease was relatively unknown just 30 years ago. After reviewing medical, health policy, and health statistical journals, I will argue in this paper that international aid to nations struggling with AIDS needs to be redirected and refocused on supplying antiretroviral therapy to afflicted nations because ARV has been proven to be effective in managing the disease in countries that can afford the costs of treatment. International aid to countries that …

Effects Of Restricted Fructose Access On Body Weight And Blood Pressure Circadian Rhythms, Danielle Senador, Swapnil Vijay Shewale, Maria Claudia Irigoyen, Khalid M. Elased, Mariana Morris

Pharmacology and Toxicology Faculty Publications

High-fructose diet is known to produce cardiovascular and metabolic pathologies. The objective was to determine whether the timing of high fructose (10% liquid solution) intake affect the metabolic and cardiovascular outcomes. Male C57BL mice with radiotelemetric probes were divided into four groups: (1) 24 h water (control); (2) 24 h fructose (F24); (3) 12 h fructose during the light phase (F12L); (4) 12 h fructose during the dark phase (F12D). All fructose groups had higher fluid intake. Body weight was increased in mice on restricted access with no difference in total caloric intake. Fasting glycemia was higher in groups with …

The Fate Of Sulfamethazine In Sodium-Hypochlorite-Treated Drinking Water: Monitoring By Lc-Msn-It-Tof, Tyler C. Melton, Stacy D. Brown

ETSU Faculty Works

Pharmaceutical compounds represent a rapidly emerging class of environmental contaminants. Such compounds were recently classified by the U.S. Geological Survey, including several antibiotics. An LC-MS/MS screening method for the top five antibiotics in drinking water was developed and validated using a Shimadzu LC-MS-IT-TOF. The separation was performed using a Waters Acquity UPLC BEH C18 column with a gradient elution. Sulfamethazine was exposed to conditions intended to mimic drinking water chlorination, and samples were collected and quenched with excess sodium sulfite. Kinetics of sulfamethazine degradation was followed as well as the formation of the major chlorinated byproduct (m/z 313). For the …

Inhibition Of Adhesion And Invasion Of Pseudomonas Aeruginosa To Lung Epithelial Cells: A Model Of Cystic Fibrosis Infection, Ayman Noreddin, Ghada Sawy, Walid Elkhatib, Ehab Noreddin, Atef Shibl

Pharmacy Faculty Books and Book Chapters

"Over their life time, CF patients experience multiple infections by various pneumoniacausing bacteria [6]. With more patients surviving to adulthood, chronic infections with Pseudomonas aeruginosa are coming to the forefront as a leading cause of death [7]. Problems presented by infected CF lung are multi-dimensional; the electrolyte balance and pH of the fluids are abnormal. The mucus is thick and of an alternative composition compared to normal lung and may contribute to colonization with Pseudomonas aeruginosa [2, 3, 5]. As such, research is multi-pronged and includes gene therapy to correct the defective protein, amelioration of inflammatory response and thinning of …

Reversed Chloroquine Molecules As A Strategy To Overcome Resistance In Malaria, David H. Peyton

Chemistry Faculty Publications and Presentations

This short review tells the story of how Reversed Chloroquine drugs (RCQs) were developed. These are hybrid molecules, made by combining the quinoline nucleus from chloroquine (CQ) with moieties which are designed to inhibit efflux via known transporters in the membrane of the digestive vacuole of the malaria parasite. The resulting RCQ drugs can have potencies exceeding that of CQ, while at the same time having physical chemical characteristics that may make them favorable as partner drugs in combination therapies. The need for such novel antimalarial drugs will continue for the foreseeable future.

The Mechanical Behavior Of Mutant K14-R125p Keratin Bundles And Networks In Neb-1 Keratinocytes, Daniel R. Beriault, Oualid Haddad, John V. Mccuaig, Zachary J. Robinson, David Russell, E. Birgitte Lane, Douglas S. Fudge

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Epidermolysis bullosa simplex (EBS) is an inherited skin-blistering disease that is caused by dominant mutations in the genes for keratin K5 or K14 proteins. While the link between keratin mutations and keratinocyte fragility in EBS patients is clear, the exact biophysical mechanisms underlying cell fragility are not known. In this study, we tested the hypotheses that mutant K14-R125P filaments and/or networks in human keratinocytes are mechanically defective in their response to large-scale deformations. We found that mutant filaments and networks exhibit no obvious defects when subjected to large uniaxial strains and have no negative effects on the ability of human …

Biophysical Characterization Of A Riboflavin-Conjugated Dendrimer Platform For Targeted Drug Delivery, Amanda B. Witte, Christine M. Timmer, Jeremy J. Gam, Seok Ki Choi

University Faculty Publications and Creative Works

The present study describes the biophysical characterization of generation-five poly(amidoamine) (PAMAM) dendrimers conjugated with riboflavin (RF) as a cancer-targeting platform. Two new series of dendrimers were designed, each presenting the riboflavin ligand attached at a different site (isoalloxazine at N-3 and d-ribose at N-10) and at varying ligand valency. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) were used to determine the binding activity for riboflavin binding protein (RfBP) in a cell-free solution. The ITC data shows dendrimer conjugates have K D values of ≥465 nM on a riboflavin basis, an affinity ∼93-fold lower than that of free riboflavin. …

Biophysical Characterization Of A Riboflavin-Conjugated Dendrimer Platform For Targeted Drug Delivery, Amanda B. Witte, Christine M. Timmer, Jeremy J. Gam, Seok Ki Choi

University Faculty Publications and Creative Works

The present study describes the biophysical characterization of generation-five poly(amidoamine) (PAMAM) dendrimers conjugated with riboflavin (RF) as a cancer-targeting platform. Two new series of dendrimers were designed, each presenting the riboflavin ligand attached at a different site (isoalloxazine at N-3 and d-ribose at N-10) and at varying ligand valency. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) were used to determine the binding activity for riboflavin binding protein (RfBP) in a cell-free solution. The ITC data shows dendrimer conjugates have K D values of ≥465 nM on a riboflavin basis, an affinity ∼93-fold lower than that of free riboflavin. …

Gold Ion–Angiotensin Peptide Interaction By Mass Spectrometry, Jenny Lee '13, Lasanthi P. Jayathilaka, Shalini Gupta, Jin-Sheng Huang, Bao- Shiang Lee

Student Publications & Research

Stimulated by the interest in developing gold compounds for treating cancer, gold ion– angiotensin peptide interactions are investigated by mass spectrometry. Under the experimental conditions used, the majority of gold ion–angiotensin peptide complexes contain gold in the oxidation states I and III. Both ESI-MS and MALDI-TOF MS detect singly/multiply charged ions for mononuclear/multinuclear gold-attached peptides, which are represented as [peptide+a Au (I)+b Au(III)+(e - a -3b) H]e+, where a,b≥0 and e is charge. ESI-MS data shows singly/multiply charged ions of Au(I)-peptide and Au(III)-peptide complexes. This study reveals that MALDITOF MS mainly detects singly charged Au(I)-peptide complexes, presumably due to the …

Cryo-Em Structure Of The Archaeal 50s Ribosomal Subunit In Complex With Initiation Factor 6 And Implications For Ribosome Evolution, Basil J. Greber, Daniel Boehringer, Vlatka Godinic-Mikulcic, Ana Crnkovic, Michael Ibba, Ivana Weygand-Durasevic, Nenad Ban

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 Å resolution using cryo-electron microscopy (EM). The …

Roles Of Trna In Cell Wall Biosynthesis, Kiley Dare, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Recent research into various aspects of bacterial metabolism such as cell wall and antibiotic synthesis, degradation pathways, cellular stress, and amino acid biosynthesis has elucidated roles of aminoacyl‐transfer ribonucleic acid (aa‐tRNA) outside of translation. Although the two enzyme families responsible for cell wall modifications, aminoacyl‐phosphatidylglycerol synthases (aaPGSs) and Fem, were discovered some time ago, they have recently become of intense interest for their roles in the antimicrobial resistance of pathogenic microorganisms. The addition of positively charged amino acids to phosphatidylglycerol (PG) by aaPGSs neutralizes the lipid bilayer making the bacteria less susceptible to positively charged antimicrobial agents. Fem transferases utilize …

Ginkgo Extract Egb761 Confers Neuroprotection By Reduction Of Glutamate Release In Ischemic Brain, Alexander Mdzinarishvili, Rachita K. Sumbria, Dorothee Lang, Jochen Klein

Pharmacy Faculty Articles and Research

Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema …

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 …

Chemical Hazards Emergency Medical Management (Chemm), Emily Vardell

Faculty Research, Publications, and Presentations

The Chemical Hazards Emergency Medical Management (CHEMM) website from the National Library of Medicine is designed for first responders and medical providers who are planning for and responding to chemical hazards events. It includes pages tailored to the individual interests of specific groups, including first responders, health care providers, mental health professionals, toxicologists, and more. The featured decision support system CHEMM Intelligent Syndromes Tool allows users to identify the chemical a patient was exposed to in a mass casualty event.

Chapter 12: Drinking, In Intimacy And Community In A Changing World: Sikaiana Life 1980-1993, William Donner

Sikaiana Ethnography

The role or alcohol consumption among the Sikaiana, Solomon Islands. This is an account from 1980 to 1993 and the Sikaiana do not drink as heavily at present (2020). The chapter discusses the manner in which alcohol was integrated into Sikaiana life from 1980-1993.

A related site can be found at www.sikaianaarchives.com

A Mechanistic Study Of S-Adenosyl-L-Methionine Protection Against Acetaminophen Hepatotoxicity, James Michael Brown

Theses, Dissertations and Capstones

Acetaminophen (APAP) toxicity remains the leading cause of drug induced liver failure in the United States. The current therapy for APAP toxicity is N-acetylcysteine (NAC). NAC must be administered within eight hours of APAP overdose for maximum efficacy. That, coupled with the fact that APAP toxicity may not be overtly evident, makes an alternative therapeutic intervention worth exploring. Previous work by our laboratory has demonstrated that S-adenosyl-L-methionine (SAMe) prevents APAP toxicity when given following APAP overdose in C57Bl/6 mice at a level comparable to NAC. The focus of the current work was to examine the mechanistic aspects of this protection …

Do Photoperiodic Changes In Melatonin Secretion Detrimentally Affect The Female Reproductive Cycle?, Riki Szlafrok

The Science Journal of the Lander College of Arts and Sciences

Melatonin, better known as "the hormone of darkness," is secreted by the pineal gland during the night and helps us fall asleep. Because its internal regulation depends on light, melatonin is part of chronobiology, the study of biological mechanisms and their adaptations to lunar and solar related rhythms (Klein et al. 1991). Therefore, photoperiod changes greatly impact melatonin concentration, influencing changes in neuronal and hormonal mechanisms of the photo neuro-endocrine systems, namely reproduction. Research has shown that a disruption in the circadian rhythm of melatonin due to photoperiod changes detrimentally affects the rhythmic function of the female reproductive cycle. Research …

Melatonin And Its Effect On Learning And Memory, Nechama Leah Bauman (Cahn)

The Science Journal of the Lander College of Arts and Sciences

Melatonin is a neurohormone produced by the pineal gland and secreted into the body in a circadian rhythm. Melatonin is known to be involved in many vital body functions, including sleep, reproduction, and immune response. Exogenous melatonin, sold as over the counter natural supplements in drugstores, is commonly taken by many people to help cure various ailments. Melatonin also plays a role in the hippocampus. This paper investigates the effects of melatonin on long-term potentiation in the hippocampus. Long-term potentiation, described as a long-lasting strengthening of synapses between nerve cells, is thought to be responsible for long-term memory retention. It …

Retrospective Comparison Of The Incidence Of Acute Kidney Injury In Patients Treated With Intravenous Polymyxin B Or Intravenous Colistimethate Sodium, Rebecca A. Sumner Pharmd, Jarrod W. Kile Rph, Bcps

Department of Pharmacy

No abstract provided.

Retrospective Evaluation Of Admissions For Chemotherapy-Inducednausea, Vomiting, And Dehydration, Katelin Van Leer Pharmad, Janine Barnaby Rph, Bcop

Department of Pharmacy

No abstract provided.

Bone Health Management In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Vishnuprabha Dhanapal, David J. Reeves

Scholarship and Professional Work – COPHS

Purpose. Patients receiving androgen deprivation therapy undergo a rapid decline in bone mineral density during the first 6 to 12 months of initiating therapy. The World Health Organization has developed and implemented the Fracture Risk Assessment Tool (FRAX) to predict the ten year risk of a major fracture & hip fracture. Additionally, the National Comprehensive Cancer Network and the National Osteoporosis Foundation have developed osteoporosis guidelines. This study aims to characterize the fracture risk (based on the FRAX tool) and the current management of bone health based on national guidelines compliance.

Methods. A retrospective chart review of patients receiving a …

Successful Desensitization To Docetaxel After Severe Hypersensitivity Reactions In Two Patients, David J. Reeves, Michael J. Callahan, Gregory P. Sutton

Scholarship and Professional Work – COPHS

Purpose Two cases of successful desensitization to docetaxel after severe hypersensitivity reactions are reported.

Summary Two patients with gynecological malignancies (uterine leiomyosarcoma and ovarian adenocarcinoma) experienced severe hypersensitivity reactions with docetaxel, including flushing, numbness, sharp radiating pain, severe nausea and vomiting, apnea, and unresponsiveness. Both patients received ondansetron before docetaxel. One patient received dexamethasone, diphenhydramine, and famotidine premedication before docetaxel, as she had previously reacted to paclitaxel. Docetaxel infusions were stopped, and the reactions were treated with diphenhydramine and dexamethasone (one patient also received famotidine). After resolution of symptoms, the docetaxel was not reinitiated due to the nature of the …

Linus Pauling: Scientist Of The 20th Century, Laura Ward

Natural Sciences Student Research Presentations

This poster describes the contributions scientist Linus Pauling made to the fields of chemistry and molecular biology, including his hybridization theory.