Pharmacology Commons^™

Phytochemical And Nutritional Composition Of Vernonia Amygdalina: Antioxidant, Antidiabetic Efficacy, And Hematological Benefits, Hassan A. Adewuyi, Messiah Atapia, Emmanuel Ochonung, Sakariyau A. Waheed, Adebimpe H. Oluwatoyin, Chizoba V. Obunadike, Adeleye A. Edema, Samad Hussein, Usman A. Mohammed, Kevin L. Sebastine, Tolulope O. Jaiyeola

Chemistry & Biochemistry Faculty Publications

Vernonia amygdalina, a traditionally used medicinal plant, has been purported to possess health-promoting properties. The aim of this study is to investigate the phytochemical and nutritional composition of V. amygdalina, evaluate its antioxidant and antidiabetic efficacy, and assess its hematological benefits. Phytochemical screening, proximate analysis, antioxidant assays (DPPH, ABTS), antidiabetic evaluations in treptozotocin induced diabetic rats, and hematological assessments were conducted according to standard protocol. V. amygdalina exhibited a rich phytochemical profile, comprising flavonoids, phenolic acids, and terpenoids, alongside significant antioxidant activity (IC50 = 12.5 μg/mL) and complete source of protein. Proximate analysis revealed high protein (21.1%) and …

Tick Responses To Diverse Chemical Attractants To Enhance Tick Surveillance Methods' Efficacy, Pamela Kelman, Tyler Chavers, Emily Owens Pickle, Daniel Sonenshine, Melissa S. Nolan, Holly Gaff

Biological Sciences Faculty Publications

Amblyomma maculatum Koch (Acari: Ixodidae), Ixodes scapularis Say, and Dermacentor variabilis Say are three hard-bodied ticks responsible for vectoring pathogens that cause most human tick-borne diseases in the United States of America (USA). Tick surveillance is critical to elucidate high-risk areas for targeted vector control and public health interventions. Despite tick-borne diseases having a higher annual incidence compared to mosquito-borne diseases in the USA, tick traps used for surveillance are grossly under-developed compared to the suite of sophisticated mosquito traps available on the commercial market. This study sought to identify potential prospective tick trap improvements by evaluating the relative attraction …

Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi

Chemistry & Biochemistry Faculty Publications

We investigate switching of photoluminescence (PL) from PbS quantum dots (QDs) crosslinked with two different types of photochromic diarylethene molecules, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (1H) and 4,4'-(1-perfluorocyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (2F). Our results show that the QDs crosslinked with the hydrogenated molecule (1H) exhibit a greater amount of switching in photoluminescence intensity compared to QDs crosslinked with the fluorinated molecule (2F). With a combination of differential pulse voltammetry and density functional theory, we attribute the different amount of PL switching to the different energy levels between 1H and 2F molecules which result in different potential barrier …

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …

Innovative Approaches In The Discovery Of Aquatic Mycobacteriophages, Janis H. Doss

Biomedical Sciences Theses & Dissertations

Bacteriophages (phages), viruses that infect bacteria, have many applications in medicine, agriculture, molecular biology, and other fields. As antibiotic resistance becomes an increasing problem, interest in phages has grown. The traditional techniques of phage discovery are successful for some phages, but others require modified procedures to achieve detectable host infection.

Mycobacterium is a diverse bacterial genus characterized by a unique cell wall containing mycolic acids, which aids in survival and pathogenesis. The aims of the present research were to isolate mycobacteriophages, use bioinformatics techniques to analyze mycobacterial prophages, and combine genetic analysis with multi-well plate host range studies to identify …

Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties …

Baclofen-Induced Changes In The Resting Brain Modulate Smoking Cue Reactivity: A Double-Blind Placebo-Controlled Functional Magnetic Resonance Imaging Study In Cigarette Smokers, Ariel Ketcherside, Kanchana Jagannathan, Sudipto Dolui, Nathan Hager, Nathaniel Spilka, Chaela Nutor, Hengyi Rao, Teresa Franklin, Reagan Wetherill

Psychology Faculty Publications

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure.

Methods: In this longitudinal, …

Macrophages But Not Astrocytes Harbor Hiv Dna In The Brains Of Hiv-1-Infected Aviremic Individuals On Suppressive Antiretroviral Therapy, Allen Ko, Guobin Kang, Julian B. Hattler, Hadiza I. Galadima, Junfeng Zhang, Qingsheng Li, Woong-Ki Kim

Community & Environmental Health Faculty Publications

The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and …

Antimicrobial Efficacy And Safety Of A Novel Gas Plasma-Activated Catheter Lock Solution, Sudhir Bhatt, Poonam Mehta, Chen Chen, Dayle A. Daines, Leonard A. Mermel, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 to 8 orders of magnitude with a PAD lock for 60 min. Subsequent 24-h incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline-EDTA-ethanol lock solution for 60 …

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Biological Sciences Faculty Publications

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC₉₀) or 50% parasite killing (50% lethal dose [LD₅₀]). This mutation …

Pkc-Dependent Phosphorylation Of Enos At T495 Regulates Enos Coupling And Endothelial Barrier Function In Response To G(+) -Toxins, Feng Chen, Sanjiv Kumar, Yanfang Yu, Saurabh Aggarwal, Christine Gross, Yusi Wang, Trinad Chakraborty, Alexander D. Verin, John D. Catravas, Rudolf Lucas, Stephen M. Black, David J. R. Fulton

Bioelectrics Publications

Gram positive (G(+)) infections make up similar to 50% of all acute lung injury cases which are characterized by extensive permeability edema secondary to disruption of endothelial cell (EC) barrier integrity. A primary cause of increased permeability are cholesterol-dependent cytolysins (CDCs) of G(+)-bacteria, such as pneumolysin (PLY) and listeriolysin-O (LLO) which create plasma membrane pores, promoting Ca2+-influx and activation of PKC alpha. In human lung microvascular endothelial cells (HLMVEC), pretreatment with the nitric oxide synthase (NOS) inhibitor, ETU reduced the ability of LLO to increase microvascular cell permeability suggesting an endothelial nitric oxide synthase (eNOS)-dependent mechanism. LLO stimulated superoxide production …

Study Of Charge-Dependent Transport And Toxicity Of Peptide-Functionalized Silver Nanoparticles Using Zebrafish Embryos And Single Nanoparticle Plasmonic Spectroscopy, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess unusually high surface area-to-volume ratios and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ±+2.7 nm in diameter) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs^+ζ), negatively (Ag-CALNNS NPs^−2ζ), and more negatively charged NPs (Ag-CALNNE NPs^−4ζ), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as …

Fine Tuning A Well-Oiled Machine: Influence Of Nk1.1 And Nkg2d On Nkt Cell Development And Function, Sunil K. Joshi, Mark L. Lang

Bioelectrics Publications

Natural killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but …

Mutation In The Plasmodium Falciparum Crt Protein Determines The Stereospecific Activity Of Antimalarial Cinchona Alkaloids, Carol E. Griffin, Jonathan M. Hoke, Upeka Samarakoon, Junhui Duan, Jianbing Mu, Michael T. Ferdig, David C. Warhurst, Roland A. Cooper

Biological Sciences Faculty Publications

The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in …

Electro-Gene Transfer To Skin Using A Noninvasive Multielectrode Array, Siqi Guo, Amy Donate, Gaurav Basu, Cathryn Lundberg, Loree Heller, Richard Heller

Bioelectrics Publications

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection …

Cannabinoids: A Novel Treatment Strategy For Retinal Neurodegenerative Disorders, Sandeep Samudre

Theses and Dissertations in Biomedical Sciences

Synthetic and naturally occurring cannabinoids are known to decrease intraocular pressure (IOP). Glaucomatous damage to the retina and optic nerve progresses even after therapy to maintain normal intraocular pressure (IOP). Topical application of cannabinoids decreases IOP while not affecting blood pressure or heart rate. Based upon their effects on other tissues, we hypothesize that these analogs reduce IOP and may also confer direct neuroprotective effects on the retina, possibly via CB1 and/or CB2 receptors. The purpose of this study is to determine if the newly synthesized CB agonists, lipid soluble O-1812 (CB 1), and water soluble O-2545 (CB 1

The …

Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe

Biological Sciences Faculty Publications

A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobolograrn analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …

2-Aminoethoxydiphenyl Borate As A Prototype Drug For A Group Of Structurally Related Calcium Channel Blockers In Human Platelets, Yuliya Dobrydneva, Christopher J. Abelt, Beth Dovel, Celina M. Thadigiri, Roy L. Williams, Peter F. Blackmore

Chemistry & Biochemistry Faculty Publications

We have synthesized a series of 2-aminoethoxydiphenyl borate (2-APB, 2,2-diphenyl-1,3,2-oxazaborolidine) analogs and tested their ability to inhibit thrombin-induced Ca²⁺ influx in human platelets. The analogs were either synthesized by adding various substituents to the oxazaborolidine ring (methyl, dimethyl, tert-butyl, phenyl, methyl phenyl, and pyridyl) or increasing the size of the oxazaborolidine ring to seven- and nine-membered rings. NMR analysis of the boron-containing analogs suggests that each of them exist as a ring structure through the formation of an N -> B coordinate bond (except for the hexyl analog). The possibility that these boron-containing compounds formed dimers was also …

Development Of Single Nanoparticle Optical Assays For Imaging Single Living Cells, William John Brownlow

Chemistry & Biochemistry Theses & Dissertations

Multi-drug resistance (MDR) has been reported in both prokaryotes and eukaryotes; the pathogenic gram-negative bacteria Pseudomonas aeruginosa can extrude a variety of structurally and functionally diverse substrates via a number of membrane transport systems leading to MDR. We have developed a novel nanoparticle assay to characterize both the membrane transport system composed of the MexAB-OprM efflux pump and the membrane permeability induced by antibiotics. Gold (Au) and silver (Ag) nanoparticles were investigated for use as probes to explore membrane transport in P. aeruginosa.

The surface plasmon absorption (color) of Au nanoparticle solutions was found to change in the presence …

Investigations On The Use Of Ion Mobility Spectrometry For Clinical Chemistry Applications, Henri Parson Patten

Theses and Dissertations in Biomedical Sciences

The major objective of this research is to examine ion mobility spectrometry as a rapid screening tool for specific application to clinical chemistry research and laboratory use. Methodology was developed for target analytes representing several classes of physiologically active substances, including anesthetics, illicit drugs, and their metabolites. The IMS characteristics of animal tissues and other compounds such as amino acids and proteins were determined. Quality assurance and control procedures were developed for specific quality data objectives. Criteria were established relating to use of IMS for assessing the precision and accuracy of data, qualitative screening, and semi-quantitative analyses.

It was found …

Trans-Resveratrol Inhibits Calcium Influx In Thrombin-Stimulated Human Platelets, Yuliya Dobrydneva, Roy L. Williams, Peter F. Blackmore

Chemistry & Biochemistry Faculty Publications

1 The phytoestrogenic compound trans-resveratrol (trans-3,5,4'-trihydroxystilbene) is found in appreciable quantities in grape skins and wine. It has been shown that both products rich in trans-resveratrol and pure trans-resveratrol inhibit platelet aggregation both in vivo and in vitro. However the mechanism of this action still remains unknown.

2 An essential component of the aggregation process in platelets is an increase in intracellular free Ca²⁺ ([Ca²⁺]_i). Ca²⁺ must enter the cell from the external media through specific and tightly regulated Ca²⁺ channels in the plasma membrane. The objective …

In Situ Regulation Of Cytosolic Phospolipase A₂, Beverly A. Rzigalinski

Theses and Dissertations in Biomedical Sciences

The 85 kDa cytosolic phospholipase A₂ (cPLA₂) is an agonist-responsive effector for intracellular signal transduction through the arachidonate cascade. In vitro studies have demonstrated that this enzyme is regulated by sub-micromolar calcium and is specific for arachidonate as the sn-2 fatty acyl group of phospholipid substrates. However, very little data is available regarding in situ mechanisms which govern the activity of cPLA₂. The primarily objective of these studies was to develop an in situ system for the study of cPLA₂, and investigate mobilization of arachidonate during signal transduction events.

Dimethylsulfoxide differentiation of the …

A Biochemical Study Of Gossypol And Lactate Dehydrogenase X Binary Interactions, Patricia Brown Ravenell

Theses and Dissertations in Biomedical Sciences

The goal of this project was to study the mechanism of action of gossypol through its (a) binary interaction with native and trypsin digested lactate dehydrogenase-X (LD-X), a sperm-specific isozyme, and (b) its binding in vitro in primary cultures of spermatogenic cells. Mouse LD-X was cleaved with trypsin before and after treatment with gossypol. This was followed by high performance chromatography (HPLC) separation of the LD-X tryptic peptide fragments to observed alterations in separation patterns as indicators of intramolecular disturbance in the enzyme molecule. Definite alterations in peptide fragment peaks were observed in the presence of gossypol and suggest conformational …

The Synthesis And Evaluation Of A New Analog Of Phencyclidine (Pcp), William H. Johnson Jr.

Chemistry & Biochemistry Theses & Dissertations

Based on an interpretation of the literature of phencyclidine (PCP) together with an examination of the relevant models or prototype structures, this research has attempted to design and synthesize a rigid analog of the phencyclidine structure. The parent ring systems suggested for this study were the 1-arnino and 2-arninornethyltetralins, 10 and, 12.

Several organic compounds, based on this design, have been prepared by classical examples of reductive alkylation reactions of the corresponding 2-hydroxyciethylene-1-tetralones, 11, and by the condensation and subsequent reductive alkylation of the 1-arninotetralin, 9. These arninomethyltetralones, 28, 29 and 30, together with an example of a substituted 1-arninotetralin, …

Sulfatides As Opiate Receptors: An Evaluation Of The Opiate Binding Potential Of Sulfogalactosylgylcerolipid, Darby Geoghegan Hand

Chemistry & Biochemistry Theses & Dissertations

Cerebroside sulfate (CS) has recently been shown to bind opiate drugs in a pharmacologically relevent manner and therefore satisfy the structural requirements of an opiate receptor. Seminolipid (SGG), a novel sulfated galactosyl. glycerolipid that has been isolated from the testes of a variety of mammals, may be viewed as a structural analog of CS. In view of this structural similarity, it is reasonable to presume that SGG may also bind opiate drugs. The isolation of SGG from boar testes was accomplished using silica gel dry column chromotography with a chloroform: methanol water solvent system. The structure and purity of the …