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2015

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Articles 61 - 90 of 155

Full-Text Articles in Chemicals and Drugs

Determination Of Dioctyl Phthalate (Dehp) Concentration In Polyvinyl Chloride (Pvc) Plastic Parts Of Toothbrushes, Ghazal Sadeghi, Elham Ghaderian, Anne O'Connor May 2015

Determination Of Dioctyl Phthalate (Dehp) Concentration In Polyvinyl Chloride (Pvc) Plastic Parts Of Toothbrushes, Ghazal Sadeghi, Elham Ghaderian, Anne O'Connor

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Phthalates are chemicals that are widely used in daily products and polyvinyl chloride (PVC) plastics, mainly because of their ability to enhance flexibility and durability. The presence of phthalates in various products contributes to the substantial exposure that all consumers may experience. Continuity in phthalate exposure has several side effects, including endocrine disruption, neurological damage, asthma, hormonal imbalances, obesity, infertility, genital defects, and testicular cancer. The purpose of this research experiment was to determine the Dioctyl phthalate (DEHP) concentration of PVC plastic parts of toothbrushes. The method used to conduct the experiment was Gas Chromatography/Mass Spectrometry. The result showed that …


Custom Fluorophores For Investigating The Cellular Uptake Mechanisms And Side-Effects Of Pharmaceuticals, Yu-Hsuan Chu May 2015

Custom Fluorophores For Investigating The Cellular Uptake Mechanisms And Side-Effects Of Pharmaceuticals, Yu-Hsuan Chu

Dissertations and Theses

There is a significant current need to elucidate the molecular mechanisms of the side-effects caused by widely-used pharmaceuticals. Examples include the acute nephrotoxicity and irreversible ototoxicity promoted by the cationic drugs gentamicin and cisplatin. Gentamicin is an aminoglycoside antibiotic used for the prevention and treatment of life-threatening gram-negative bacterial infections, such as tuberculosis and meningitis. Cisplatin is used to treat a broad spectrum of cancers including head and neck, ovarian, cervical, stomach, bladder, sarcoma, lymphoma, testicular cancer and others.

The objective of this study is to design and synthesize rhodamine derivatives that can be used for the construction of geometrically …


Synthesis And Characterization Of A New Peptide Prodrug Of Glucosamine With Enhanced Gut Permeability, Hamed Gilzad Kohan, Kamaljit Kaur, Fakhreddin Jamali May 2015

Synthesis And Characterization Of A New Peptide Prodrug Of Glucosamine With Enhanced Gut Permeability, Hamed Gilzad Kohan, Kamaljit Kaur, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

The aim of this study was to synthesize a peptide prodrug of glucosamine (GlcN) with increased gut permeability through the gut peptide transporter 1 (PepT1). Glycine-Valine ester derivative of GlcN (GVG) was synthesised using solid phase synthesis followed by characterization and evaluation of its physicochemical and intestinal stability. In addition, GVG was evaluated for its ability to be biotransformed to GlcN in the liver homogenate. In vitro absorption of the new prodrug through everted rat gut was also assessed. GVG demonstrated significant and meaningful increased gut permeability as compared with GlcN. It showed favorable stability in the gut and a …


The Nonmedical Use Of Prescription Stimulants Among Students With High Academic Standing, Megan L. Dwyer May 2015

The Nonmedical Use Of Prescription Stimulants Among Students With High Academic Standing, Megan L. Dwyer

Senior Honors Projects, 2010-2019

College students report one of the highest rates of the nonmedical use of prescription stimulants (NPS). Research has shown that use is more common among students who have high levels of perceived stress, such as honors students. The purpose of this study was to determine whether honors students reported higher rates of NPS than their non-honors peers with high academic standing. It was hypothesized that honors students would report higher rates of use. The instrument used in this study was an email survey that was administered electronically through the online Qualtrics Survey system. The survey request was sent to 3,530 …


The Synthesis And Study Of The Biological And Colloidal Properties Of Bolaamphiphiles, Louis M. Damiano May 2015

The Synthesis And Study Of The Biological And Colloidal Properties Of Bolaamphiphiles, Louis M. Damiano

Senior Honors Projects, 2010-2019

Over the past decade, antibiotic resistant bacteria have caused infections in patients throughout the world.[1] The rise in antibiotic resistance is primarily due to the misuse and overuse of antibiotics. [1] To counter the increase in antibiotic resistance, infection control mechanisms have been aggressively researched in recent years. In particular, drug delivery has become a focal point to fight antibiotic resistant infections.[2] Amphiphiles have a wide range of applications in the clinical setting, including the ability to inhibit bacterial transference because of their bactericidal activity. [3] Bolaamphiphiles are a subclass of amphiphiles that possess two or more hydrophilic …


Cave Cyanobacteria Showing Antibacterial Activity, Vasiliki Lamprinou, Kyriaki Tryfinopoulou, Emmanuel N. Velonakis, Alkiviadis Vatopoulos, Smaragdi Antonopoulou, Elizabeth Fragopoulou, Adriani Pantazidou, Athena Economou-Amilli May 2015

Cave Cyanobacteria Showing Antibacterial Activity, Vasiliki Lamprinou, Kyriaki Tryfinopoulou, Emmanuel N. Velonakis, Alkiviadis Vatopoulos, Smaragdi Antonopoulou, Elizabeth Fragopoulou, Adriani Pantazidou, Athena Economou-Amilli

International Journal of Speleology

Cave Cyanobacteria - thriving in an ‘extreme’ environment with interesting species biodiversity - are supposed to be a potential source of bioactive compounds. Lipid extracts from pure cultures of two recently established Cyanobacteria from Greek caves, Toxopsis calypsus and Phormidium melanochroun, were used for antibacterial screening against human pathogenic bacteria (reference and clinical isolates). Antimicrobial Susceptibility testing for both taxa was carried out using the disc-diffusion (Kirby Bauer) method, while preliminary data applying the standard broth microdilution method for the determination of the Minimal Inhibitory Concentration (MIC) are given only for T. calypsus. Antibacterial activity was demonstrated against the …


The Effect Of An Educational Intervention On Oral Anticoagulation Therapy Knowledge In Primary Care, Elizabeth D. Deck May 2015

The Effect Of An Educational Intervention On Oral Anticoagulation Therapy Knowledge In Primary Care, Elizabeth D. Deck

Evidence-Based Practice Project Reports

It is estimated that three million people in the United States are on oral anticoagulation therapy (warfarin). Populations studied have been found in therapeutic range 64% of the time (Pernod, Labarere, & Bosson, 2008). The low percentage of therapeutic range is attributable to (a) adherence, (b) monitoring infrequency, (c) Vitamin K antagonists, and (d) the effects of aging and comorbidities. The purpose of this evidence-based practice (EBP) project was to examine whether an educational intervention would improve the knowledge of patients receiving warfarin therapy. Roy’s model for patient adaptation and the Stetler Model for EBP were used as frameworks for …


Effect Of Novel Dietary Supplement On Metabolism In Vitro And In Vivo, Robert A. Vaughan, Ailish C. White, Jason R. Beam, Nicholas P. Gannon, Randi Garcia-Smith, Roy M. Salgado, Marco Bisoffi, Kristina A. Trujillo, Carole A. Conn, Christine M. Mermier May 2015

Effect Of Novel Dietary Supplement On Metabolism In Vitro And In Vivo, Robert A. Vaughan, Ailish C. White, Jason R. Beam, Nicholas P. Gannon, Randi Garcia-Smith, Roy M. Salgado, Marco Bisoffi, Kristina A. Trujillo, Carole A. Conn, Christine M. Mermier

Health Sciences and Kinesiology Faculty Articles

Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators) on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro. Human males ingested either a placebo or commercially available supplement (RF) in a randomized double-blind placebo-controlled cross-over fashion. Metabolic rate, respiratory exchange ratio, and blood pressure were …


Effects Of Heat Stress On Arterial Compliance In Smokers: A Pilot Study, Erin Dougherty May 2015

Effects Of Heat Stress On Arterial Compliance In Smokers: A Pilot Study, Erin Dougherty

Health, Human Performance and Recreation Undergraduate Honors Theses

Arterial compliance (i.e., arterial elasticity) is a major contributor to the pathophysiology of cardiovascular disease (CVD) and has been recognized as an independent risk factor for CVD. Smokers have poor arterial compliance compared to non-smokers. In non-smokers, passive heat stress has been shown to acutely improve arterial compliance. It is unknown how passive heat stress affects arterial compliance in smokers. The purpose of this pilot study was to test the hypothesis that passive heat stress improves arterial compliance in smokers to a greater extent than non-smokers. This pilot study involved 2 male smokers and 2 male non-smokers, ages 18-21. Smokers …


Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton May 2015

Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton

Renée Crown University Honors Thesis Projects - All

Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working …


Oseltamivir-Warfarin Interaction In Hypoplastic Left Heart Syndrome: Case Report And Review., Jonathan B. Wagner, Susan M. Abdel-Rahman May 2015

Oseltamivir-Warfarin Interaction In Hypoplastic Left Heart Syndrome: Case Report And Review., Jonathan B. Wagner, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

An 8-year-old boy with hypoplastic left heart syndrome with a previous history of thrombosis within the inferior vena cava receiving stable warfarin dosing for anticoagulation was diagnosed with influenza B. He was subsequently placed on oseltamivir therapy according to the Centers for Disease Control and Prevention clinical practice guidelines. During the hospitalization, his international normalized ratio steadily increased to supratherapeutic levels and returned to baseline after discontinuation of oseltamivir therapy. This case represents a drug-drug interaction that has not been previously reported in children or adolescents. An extensive review of the pharmacokinetic and pharmacodynamic literature did not uncover a definitive …


Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families, Saleem Akhtar, Arshalooz Rehman, Surraya Bano, Anwarul Haque May 2015

Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families, Saleem Akhtar, Arshalooz Rehman, Surraya Bano, Anwarul Haque

Department of Emergency Medicine

ABSTRACT Aluminum phosphide is commonly used as a rodenticide and insecticide and is one of the most fatal poisons. The active ingredient is Phosphine gas which inhibits cytochrome oxidase and cellular oxygen utilization. The clinical symptoms are due to multiorgan involvement including cardiac toxicity which is the most common cause of mortality. Severity of clinical manifestations depends upon the amount of the gas to which a person is exposed. There is no specific antidote available. High index of suspicion and early aggressive treatment is the key to success. We report 2 cases of aluminum phosphide toxicity in 2 families due …


Distributed Drug Discovery: Synthesis Of Unnatural Amino Acids As Potential Antimalarial Drugs, Amanda Dugan May 2015

Distributed Drug Discovery: Synthesis Of Unnatural Amino Acids As Potential Antimalarial Drugs, Amanda Dugan

Honors College

Through the collaboration of many institutions across the globe, the Distributed Drug Discovery project founded at Indiana University-Purdue University Indianapolis seeks to aid in the development of drugs for the developing world. In response to two antimalarial assay hits, our team at Abilene Christian University has synthesized many unnatural amino acid analogs using resin-based combinatorial chemistry. Proton nuclear magnetic resonance spectroscopy has been used to characterize the compounds and thin layer chromatography to determine purity. All compounds were purified on hypersep cyanosilica columns.


Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah May 2015

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …


Evaluation Of Bde-47 And -99 Lipid Modulating Effects In Hepg2 Human Carcinoma Cells, Eileen A. Holovac May 2015

Evaluation Of Bde-47 And -99 Lipid Modulating Effects In Hepg2 Human Carcinoma Cells, Eileen A. Holovac

Senior Honors Projects

Non-alcoholic fatty liver disease (NAFLD) is becoming a significantly more common problem in today’s society, affecting up to 25% of people in the United States as reported by the American Liver Foundation. According to the American Association of the Study of Liver Diseases, NAFLD is the buildup of fat in the liver that is not caused by secondary factors such as alcohol consumption, hereditary disorders, or the use of steatogenic medication such as amioderone. A liver is considered fatty when 5-10% of the liver’s weight is fat. The progression of NAFLD can lead to cirrhosis, liver cancer, or liver failure. …


Raman Micro Spectroscopy For In Vitro Drug Screening: Subcellular Localisation And Interactions Of Doxorubicin, Zeineb Farhane, Franck Bonnier, Alan Casey, Hugh Byrne May 2015

Raman Micro Spectroscopy For In Vitro Drug Screening: Subcellular Localisation And Interactions Of Doxorubicin, Zeineb Farhane, Franck Bonnier, Alan Casey, Hugh Byrne

Articles

Vibrational spectroscopy, including Raman spectroscopy, has been widely used over the last few years to explore potential biomedical applications. Indeed, Raman spectroscopy has been demonstrated to be a powerful non-invasive tool in cancer diagnosis and monitoring. In confocal microscopic mode, the technique is also a molecularly specific analytical tool with optical resolution which has potential applications in subcellular analysis of biochemical processes, and therefore as an in vitro screening tool of the efficacy and mode of action of, for example, chemotherapeutic agents.

In order to demonstrate and explore the potential in this field, established, model chemotherapeutic agents can be valuable. …


Estrogen, Bisphenol A, And Bisphenol S: Regulation Of Cathepsin L Activity And Its Relation To Systemic Lupus Erythematosis, Regina M. Powers Apr 2015

Estrogen, Bisphenol A, And Bisphenol S: Regulation Of Cathepsin L Activity And Its Relation To Systemic Lupus Erythematosis, Regina M. Powers

Biology Honors Papers

Systemic Lupus Erythematosis (SLE) is an autoimmune disease that causes the immune system to self-destruct. SLE is nine times more frequent in women than in men, and it has been shown that there is a correlation between high estrogen levels and an increased severity of the disease. This raises a concern about environmental estrogens, including Bisphenol A (BPA) which is found in many plastic products in the United States. BPA can be absorbed by the foods and liquids that are held in the plastic containers and then can enter into the human body. Because of its structural similarity to estrogen, …


The Regulation Of Cathepsin L Activity By Estrogen And Bisphenols A & S: Relationship To Systemic Lupus Erythematosus, Dylan T. Cuva Apr 2015

The Regulation Of Cathepsin L Activity By Estrogen And Bisphenols A & S: Relationship To Systemic Lupus Erythematosus, Dylan T. Cuva

Biology Honors Papers

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that is linked to increased levels of estrogen. Bisphenol A (BPA) is an environmental estrogen that may also play a role in SLE. BPA is used in the production of polycarbonate plastics and epoxy resins, including use in the creation of cans and plastic bottles. This study investigated the role of BPA and other bisphenols on enzyme activity in a murine model for SLE.


Fda Approves 18 New Molecular Entities/Biologics, Rodney Richmond Apr 2015

Fda Approves 18 New Molecular Entities/Biologics, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.


Synthesis Of Β-Triphosphotriester Pronucleotides, Yousef A. Beni, Chandravanu Dash, Keykavous Parang Apr 2015

Synthesis Of Β-Triphosphotriester Pronucleotides, Yousef A. Beni, Chandravanu Dash, Keykavous Parang

Pharmacy Faculty Articles and Research

Dinucleoside phosphorochloridite were synthesized from phosphorus trichloride and three nucleoside analogues, 3-fluoro-2,3-dideoxythymidine (FLT), 2',3'-dideoxy-5-fluoro-3'- thiacytidine (FTC), and 2',3'-dideoxy-3'-thiacytidine (3TC), in a multistep synthesis. Polymerbound N-Boc p-acetoxybenzyl 5¢-O-2¢-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the b-triphosphotriester derivatives containing three different nucleosides.


The Effects Of Adderall On Maternal And Fetal Health, Alyson Brady Apr 2015

The Effects Of Adderall On Maternal And Fetal Health, Alyson Brady

Honors Theses

Information available for woman prescribed Adderall to treat ADHD and the effects that it may have on her fetus is limited. However, Adderall and methamphetamine have similar pharmacological and addictive qualities. This paper is concerned with whether there is an adequate approach to treatment that balances the needs of the mother and the fetus. With Adderall use becoming more prevalent, it is essential that society is aware of the physiology and pharmacology of this drug, as well as, the need for more research on this subject to be produced.


Effects Of Bpa And Alternatives On Human Health Concerning The Nflpa, Jeremy Martell Apr 2015

Effects Of Bpa And Alternatives On Human Health Concerning The Nflpa, Jeremy Martell

Biology Undergraduate

No abstract provided.


Flavour Chemicals In Electronic Cigarette Fluids, Peyton A. Tierney, Clarissa D. Karpinski, Jessica E. Brown, Wentai Luo, James F. Pankow Apr 2015

Flavour Chemicals In Electronic Cigarette Fluids, Peyton A. Tierney, Clarissa D. Karpinski, Jessica E. Brown, Wentai Luo, James F. Pankow

Chemistry Faculty Publications and Presentations

Background: Most e-cigarette liquids contain flavour chemicals. Flavour chemicals certified as safe for ingestion by the Flavor Extracts Manufacturers Association may not be safe for use in e-cigarettes. This study identified and measured flavour chemicals in 30 e-cigarette fluids.

Methods: Two brands of single-use e-cigarettes were selected and their fluids in multiple flavour types analysed by gas chromatography/mass spectrometry. For the same flavour types, and for selected confectionary flavours (eg, bubble gum and cotton candy), also analysed were convenience samples of e-cigarette fluids in refill bottles from local ‘vape’ shops and online retailers.

Results: In many liquids, total flavour chemicals …


Investigation Of Dual Stage Acridones As A Potent Malaria Treatment, Stephanie Huezo Apr 2015

Investigation Of Dual Stage Acridones As A Potent Malaria Treatment, Stephanie Huezo

Dissertations, Masters Theses, Capstones, and Culminating Projects

The need for potent antimalarials to prevent the emergence of drug resistant Plasmodium falciparum is urgent. Discovery of novel acridone chemotypes have shown promise for a new antimalarial drug treatment. Presently, two acridone chemotypes have intrinsic antimalarial potency against chloroquine sensitive and multidrug resistant parasites. Acridones lacking an N10 side chain are known as chemotype I acridones, whereas, chemotype II acridones are defined as having an alkyl side chain at the same position. The N10 substitution of chemotype II acridones is thought to target heme and inhibit hemozoin formation within the parasite’s digestive vacuole, and is known to provide synergistic …


Drug Testing Government Assistance Recipients, Justin Galles Apr 2015

Drug Testing Government Assistance Recipients, Justin Galles

Nebraska College Preparatory Academy: Senior Capstone Projects

Eligibility for government assistance is based on income levels and is generally given to single parents and lower income families. Government assistance programs like welfare, SNAP (food stamps), and unemployment all help support people who have less income than what is necessary to support themselves and or their families. Programs like welfare and unemployment give checks that can be cashed and used at the discretion of the recipient. Who is to say recipients aren’t spending tax payer dollars on illegal drugs? People aren’t going to admit to government officials that they use illegal drugs so to be sure that they …


Effects Of Cannabidiol On Contractions And Calcium Signaling In Rat Ventricular Myocytes, Ramez M. Ali, Lina T. Al Kury, Keun-Hang Susan Yang, Anwar Qureshi, Mohanraj Rajesh, Sehamuddin Galadari, Yaroslav M. Shuba, Frank Christopher Howarth, Murat Oz Apr 2015

Effects Of Cannabidiol On Contractions And Calcium Signaling In Rat Ventricular Myocytes, Ramez M. Ali, Lina T. Al Kury, Keun-Hang Susan Yang, Anwar Qureshi, Mohanraj Rajesh, Sehamuddin Galadari, Yaroslav M. Shuba, Frank Christopher Howarth, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the Ca2+ sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca2+ currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1 μM) caused a significant decrease in the amplitudes of …


Does The Addition Of Dexamethasone To Local Anesthetic Used For Peripheral Nerve Block Prolong Analgesia In The Surgical Patient?, Janice M. Oliveira Apr 2015

Does The Addition Of Dexamethasone To Local Anesthetic Used For Peripheral Nerve Block Prolong Analgesia In The Surgical Patient?, Janice M. Oliveira

Nurse Anesthesia MSNA Student Capstones

Pain after orthopedic surgery can be intense. Many anesthesia providers and orthopedic surgeons support the use of peripheral nerve blockade to assist in decreasing the amount of pain a patient may experience post operatively. Select medication adjuncts are being added to peripheral nerve blocks to prolong analgesia. The research presented here focuses on the addition of dexamethasone to peripheral nerve blocks to prolong analgesia. Dexamethasone is a synthetic glucocorticoid that acts as an anti-inflammatory. It has been shown to inhibit the release of inflammatory mediators such as, interleukins and cytokines, facilitating the release of anti-inflammatory mediators, decreasing postoperative pain. Recent …


Minimal Opioid Anesthetic In Patient With History Of Substance Abuse: A Case Study, Sarah E. Varney Apr 2015

Minimal Opioid Anesthetic In Patient With History Of Substance Abuse: A Case Study, Sarah E. Varney

Nurse Anesthesia MSNA Student Capstones

More than half of the population in the United States of America drinks alcohol regularly. Thousands of deaths annually are linked to drug overdoses, and that number continues to rise. Anesthesia professionals can expect to see patients in various levels of substance abuse and recovery during their practice. This case study is presented to discuss a minimal narcotic technique given in a patient with a history of prescription drug abuse, who had been substance free since successfully been through a recovery program years prior.


High Potency Eugeroics-- Wake-Promoting Agents Beyond Modafinil, Joseph Yoham Apr 2015

High Potency Eugeroics-- Wake-Promoting Agents Beyond Modafinil, Joseph Yoham

Biomedical Engineering

Modafinil (Provigil) belongs to a new pharmaceutical class known as eugeroics— wake-promoting agents. Directly enhancing conductance across neuronal membranes, modafinil, amplifies presynaptic Na/Ca influx; resultant widespread depolarization of cortical interneurons could theoretically allow transient, voltage-dependent inhibition of monoamine reuptake- resembling action of conventional stimulants, minus the stereotypy, euphoria, and locomotor effects. This literature review presents a hypothesized mechanism of action, consolidates research of modafinil analogues and hybridizes a novel compound in search of a next generation molecule.


Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko Mar 2015

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …