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Targeting Therapy To The Neuromuscular Junction: Proof Of Concept, Linda L. Kusner, Namita Satija, Georgiana Cheng, Henry J. Kaminski

Pharmacology and Physiology Faculty Publications

Introduction: The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ.

Methods: A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG.

Results: Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally …

Evidence That Bdnf Regulates Heart Rate By A Mechanism Involving Increased Brainstem Parasympathetic Neuron Excitability, Ruqian Wan, Letitia A. Weigand, Ryan Bateman, Kathleen Griffioen, David Mendelowitz, Mark P. Mattson

Pharmacology and Physiology Faculty Publications

Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haploinsufficiency exhibit elevated resting heart rate, and infusion of BDNF intracerebroventricularly reduces heart rate in both wild-type and BDNF+/− mice. The atropine-induced elevation of heart rate is diminished in BDNF+/− mice and is restored by BDNF infusion, whereas …

Genomics Into Healthcare: The 5th Pan Arab Human Genetics Conference And 2013 Golden Helix Symposium., Paolo Fortina, Najib Al Khaja, Mahmoud Taleb Al Ali, Abdul Rezzak Hamzeh, Pratibha Nair, Federico Innocenti, George P. Patrinos, Larry J. Kricka

Department of Cancer Biology Faculty Papers

The joint 5th Pan Arab Human Genetics conference and 2013 Golden Helix Symposium, "Genomics into Healthcare" was coorganized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in collaboration with the Golden Helix Foundation (http://www.goldenhelix.org) in Dubai, United Arab Emirates from 17 to 19 November, 2013. The meeting was attended by over 900 participants, doctors and biomedical students from over 50 countries and was organized into a series of nine themed sessions that covered cancer genomics and epigenetics, genomic and epigenetic studies, genomics of blood and metabolic disorders, cytogenetic diagnosis and molecular profiling, next-generation sequencing, consanguinity and hereditary diseases, clinical genomics, …

The Role Of Amp-Activated Protein Kinase (Ampk) In Regulating The Early Stages Of Acute Pancreatitis, Mohamed Shitia

Honors Scholar Theses

Acute pancreatitis is an inflammatory disease that is initiated by the activation and retention of digestive zymogens inside pancreatic acinar cells (acini). It is proposed that adenosine monophosphate-activated protein kinase (AMPK) regulates early responses of acute pancreatitis in acini. A recent study shows that induction of experimental pancreatitis in isolated rat acini with supraphysiologic cerulein (orthologue of cholecystokinin) increases intracellular zymogen activation, but decreases AMPK levels. Furthermore, in vitro pharmacologic stimulation of AMPK reduces zymogen activation, having a protective effect. In this study, the effectiveness of two AMPK activators was examined in two separate in vivo pancreatitis models. In the …

The Reversal Effects Of Curcumin, An Herbal Remedy, On The Impairments Induced By Vmat-2 Inhibitor Tetrabenazine, Emily Qian, Samantha E. Yohn

Honors Scholar Theses

Substantial evidence has shown that dopamine (DA), particularly in the nucleus accumbens (NAc), is involved in behavioral activation and effort-related processes, such as overcoming work related response costs. Interference with accumbens DA transmission through administration of the vesicular monoamine transportor-2 (VMAT-2) inhibitor tetrabenazine (TBZ) produces an alteration of response allocation in the concurrent FR5/chow choice procedure, biasing animals toward the lower effort alternative. It has been suggested that these drug-induced shifts in effort-related choice behavior seen in rodents are analogous to symptoms such as psychomotor retardation, anergia, and fatigue, which can be observed in people with depression and other related …

Antioxidant Gene Therapy Against Neuronal Cell Death, Juliana Navarro-Yepes, Laura Zavala-Flores, Anandhan Annadurai, Fang Wang, Maciej Skotak, Namas Chandra, Ming Li, Aglaia Pappa, Daniel Martinez-Fong, Luz Maria Del Razo, Betzabet Quintanilla-Vega, Rodrigo Franco

Department of Psychology: Faculty Publications

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated inmitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. …

Cyclic Nucleotide-Dependent Phosphorylation Regulates Bk-Ca Channel Activity In Human Coronary Artery Smooth Muscle Cells, Raeonda Williams

PCOM Biomedical Studies Student Scholarship

Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. We have demonstrated that gonadal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKca) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) I dephosphorylation (via phosphoprotein phosphatase 2A, PP2A) regulates BKca channel activity in human coronary artery smooth muscle …

Life History Tradeoffs And The Costs Of Reproduction In Arizona Bark Scorpions (Centruroides Sculpturatus), Michael Marie Webber

UNLV Theses, Dissertations, Professional Papers, and Capstones

Tradeoffs in life history evolution result from conflicts in the time and energy that can be simultaneously invested in activities such as growth, reproduction, and survival. Reproduction is an energetically costly activity for organisms, and is known to elicit alterations in the daily activity patterns of individuals. I investigated reproductive tradeoffs in the Arizona Bark Scorpion,Centruroides sculpturatus. To better understand the nature of tradeoffs in this species, I examined the influence of reproductive state on the predatory efficiency and thermal preference of reproductive females. Further, I examined the influence of reproductive activities (i.e. gestation) on the ability of reproductive females …

The Grass Shrimp, Palaemonetes, Pugio: Hypoxic Influences On Embryonic Development, Christensen C. Javier

UNLV Theses, Dissertations, Professional Papers, and Capstones

Grass shrimp,Palaemonetes pugio, can survive in brackish waters and estuarine ecosystems despite the frequent oscillations and fluctuations in salinity, temperature and oxygen. AdultP. pugiohave the ability to osmoregulate (Romney and Reiber 2011), change cardiac parameters to tolerate temperatures (not yet published, Mika and Reiber) and oxyregulate (Guadagnoli and Reiber 2013). Manipulation of cardiac parameters allows for these methods of regulation. However, cardiac contraction and internal convection of oxygen do not occur until later stages of embryonic development. Studies focused on these morphological and physiological advantages may provide further understanding of the regulatory mechanisms within grass shrimp embryos, larvae and adults. …

Molecular Characterization Of Glioblastoma Cancer Stem Cells, Jo Meagan Garner

Theses and Dissertations (ETD)

Malignant gliomas are locally aggressive, highly vascular tumors that have an overall survival time less than 14 months, and current therapies provide little improvement in the disease course and outcome. While glioblastoma multiforme (GBM) patients present uniform histological phenotypes, the molecular determinants of the disease vary considerably between individual cases resulting in complicated prognosis. The heterogeneity, aggressiveness and rapid tumor relapse of GBM is believed to be sustained by cancer stem-like cell populations that are able to initiate and maintain tumors. Although CSCs represent only a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance …

Preliminary Study On How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz In The Developing Mouse Brain, Yu He

Theses and Dissertations (ETD)

Normal brain development requires precise coordination of neural progenitor proliferation and differentiation, the mechanism of which is not well known. Recently the tumor suppressor neurofibromatosis 2 (Nf2) was shown to regulate the balance of neural progenitor proliferation and differentiation in the developing mouse brain through the Hippo pathway effectors, transcriptional coactivators Yap/Taz. The molecular mechanism of how Nf2 regulates Yap/Taz is not understood. Here I showed that Nf2 regulated the Yap/Taz activity by decreasing the stability of Yap/Taz. The regulation was independent of Yap-S366 phosphorylation, which is required for Yap degradation. I also showed that Nf2 did not regulate Lats1/2 …

Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar

Theses and Dissertations (ETD)

The transcription factor GATA2 is highly expressed in hematopoietic stem cells (HSCs) and is downregulated during differentiation. Overexpression of GATA2 is frequently observed in acute myeloid leukemia. In previous studies, enforced expression of GATA2 using a MSCV GATA2 retroviral vector blocked differentiation of HSC and progenitors without inducing leukemia. We hypothesized that a lower dose of GATA2 can relieve the HSC block and eventually transform myeloid progenitors into leukemia stem cells. To test this hypothesis we generated a MSCV GATA2-ERT vector in which nuclear concentration of GATA2 can be regulated by Tamoxifen (TAM). The GATA2-ERT protein was confirmed to leak …

Characterization Of Cre Mouse Models To Target Cns Barriers For Generating Conditional Knockouts Of Abc Transporters, Rachel L. Scheib

Theses and Dissertations (ETD)

The central nervous system (CNS) includes the brain and spinal cord, where both possess a blood to brain and a blood to cerebrospinal fluid (CSF) barrier. The blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) regulate the passage of many molecules to maintain and protect these sensitive organs from harmful xenobiotics (i.e. drugs, pollutants, etc.) or physiologic changes (i.e. glucose, ion, or water composition). These barriers also express ABC transporters, including P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP), which are known to contribute to efflux of endogenous toxins and therapeutics from the CNS. Pgp and BCRP expression and activity are …

Adenosine Production Is Essential For Closing The Critical Period Of Cortical Plasticity, Rachel A. Chassan

Theses and Dissertations (ETD)

Sensory inputs from the external world are represented as highly organized systems in the adult brain for effective adaptation to the environment. At the cortical level, this organization is referred to as cortical maps. The establishment of cortical maps begins with early life experiences during the critical period, a brief period during development of heightened sensitivity to sensory stimuli. During this time, organization of cortical maps is plastic and highly subject to change through passive sensory experience. As an animal matures, the critical period closes and changes to cortical maps occur less freely. The cellular mechanisms of cortical map plasticity …

Assessing The Relationship Between The Blood-Air Partition Coefficient And Fractional Uptake Of Inspired Halothane, Acetone, And Ethanol Vapors In The Airways Of The C57bl/6j Mouse, Joshua Baruch Baldino

Honors Scholar Theses

The following series of studies investigates the elimination and uptake trends of halothane, acetone, and ethanol vapors in the airways of C57BL/6J mice. These vapors were chosen because they span a wide range of solubilities, as indicated by their blood-air partition coefficients, and are not associated with any significant airway metabolism or reactivity with tissue substrates in vivo. Mice were exposed to a homogeneous vapor mixture containing a 1:1:1 ratio of halothane, acetone, and ethanol at relative concentrations of approximately 10 ppm. Exposure studies were performed with mice in two states, conscious and deceased, in order to provide control …

Development Of A Multi-Purpose Automated Synthesis Module For Production Of Novel Pet Radiopharmaceuticals, I Hong Shih

Dissertations and Theses (Open Access)

Among radiopharmaceuticals of positron emission tomography (PET), ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) made from commercialized automated synthesis module is the most frequently used in tumor diagnoses. But the false positive findings, such as infectious tissues and post-operative surgical conditions, show strong uptake of ¹⁸F-FDG in PET scans which requires extra clinical procedures to confirm the results. Moreover, the false negative findings, such as low glycolytic activity tumors, reduce the accuracy of PET scans. Therefore, there will be new PET radiopharmaceuticals to redeem the defects of ¹⁸FDG-PET applications.

Current commercialized automated synthesis modules are suitable for clinical use, but …

Eye-Tracking Measures Of Attentional Bias In Cocaine Dependent Subjects, Nadeeka Dias

Dissertations and Theses (Open Access)

Cocaine-dependent (CD) subjects show evidence of attentional bias toward cocaine-related cues, and this measure of cue-reactivity is predictive of craving and relapse. In previous work, cue-reactivity and attentional bias have been assessed by models that present drug-relevant stimuli (e.g., cocaine-specific Stroop task) and measure physiological and behavioral reactivity (e.g., heart rate, reaction times). Studies have indicated competition between the higher-order cortical processes (frontal eye-fields, DLPFC) in voluntary eye control (i.e., anti-saccades) and more reflexive saccades driven by involuntary midbrain (superior colliculus) perceptual input (i.e., pro-saccades). In addition, neuroimaging studies in patients with cocaine dependence have shown activation in frontal regions …

Performance Evaluation Of Material Decomposition Using Rapid Kvp-Switching Dual-Energy Ct For Assessing Bone Mineral Density, John M. Wait

Dissertations and Theses (Open Access)

Osteoporosis is diagnosed by assessing the bone mineral density (BMD) of the trabecular bone, and has previously been characterized with dual-energy x-ray absorptiometry (DXA) or single-energy computed tomography (SECT). Dual-energy computed tomography (DECT) is able to create two three-dimensional sets of images representing the densities of two materials in a given basis pair. DECT is theoretically capable of providing a true density measurement of trabecular bone material with the proper material basis pair.

Using the rapid kVp-switching GE HD750 scanner, the concentrations of various solutes were assessed in two-material syringe-phantoms in different experimental conditions with DECT material density images, SECT …

Extracellular Ubiquitin: Role In Cardiac Myocyte Apoptosis And Myocardial Remodeling, Christopher Ray Daniels

Electronic Theses and Dissertations

Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling …

Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu

Electronic Theses and Dissertations

Innate immune and inflammatory responses contribute to myocardial and cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLRs) play a critical role in the induction of innate immune and inflammatory responses via activation of nuclear factor kappa B (NF-κB). We have shown that activation of NF-κB contributes to myocardial and cerebral I/R injury. Indeed, inhibition of TLR4-mediated NF-κB activation significantly decreased myocardial and cerebral I/R injury via activation of PI3K/Akt signaling. PI3K/Akt signaling is an important pathway in regulating cellular survival and inflammatory responses. Therefore, an important question is how to differentially modulate PI3K/Akt signaling and TLR/NF-κB-mediated signaling pathway during I/R injury? …

The Role Of Glutamate Signalling In Diabetic Neuropathy, Nadia Hussain

Dissertations

The majority of diabetics develop neuropathy, which can be debilitating, but the underlying pathophysiological mechanisms are poorly understood. Diabetic neuropathy progresses in a distal to proximal manner. Previous studies have shown that glutamate, the most common excitatory neurotransmitter, plays a role in the pathogenesis of neuropathy. The reason why the role of glutamate in nociception becomes a problem in diabetes and the mechanisms that are involved are unknown. Based on the preliminary data, the hypothesis was that glutamate pathways are likely to be involved in diabetic neuropathy particularly neuropathic pain. Pathways were investigated to look for changes that might reflect …

Hypoxic Signals In The Ischemic Myocardium: Role Of Galectin-1 And Galectin-3, Satwat Hashmi

Dissertations

Myocardial infarction is the most serious manifestation of coronary artery disease and the cause of significant levels of mortality and morbidity worldwide. Galectin-1 (GAL-1) and Galectin-3 (GAL-3) are beta galactoside binding lectins with diverse functions. Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor mediating early and late responses to myocardial ischemia. We aim to study the direct effects of ischemia on GAL-1, GAL-3 and HIF-1α in the heart. Male C57B6/J and GAL-3 knockout mice were used for our two disease models. In the Myocardial infarction (MI) model, the left anterior descending artery of the heart is permanently ligated to …

Suppression Of Basophil Histamine-Release And Other Ige-Dependent Responses In Childhood Schistosoma Mansoni Hookworm Co-Infection, Angela Pinot De Moira, Colin M. Fitzsimmons, Frances M. Jones, Shona Wilson, Pierre Cahen, Edridah Tukahebwa, Harriet Mpairwe, Joseph K. Mwatha, Jeffrey M. Bethony, Per S. Skov, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. The poor correlation between allergen-specific-IgE (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.

Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Non-specific (anti-IgE), helminth-specific and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment.

Results. Non-specific- and helminth-specific-HR, and associations between helminth-specific-IgE and helminth-specific-HR increased post-treatment. Hookworm infection appeared …

Tumor Microenvironment-Based Feed-Forward Regulation Of Nos2 In Breast Cancer Progression, Julie L. Heinecke, Lisa A. Ridnour, Robert Y.S. Cheng, Christopher H. Switzer, Michael M. Lizardo, Chand Khanna, Sharon A. Glynn, S. Perwez Hussain, Howard A. Young, Stefan Ambs, David A. Wink

United States Public Health Resources

Inflammation is widely recognized as an inducer of cancer progression. The inflammation-associated enzyme, inducible nitric oxide synthase (NOS2), has emerged as a candidate oncogene in estrogen receptor (ER)-negative breast cancer, and its increased expression is associated with disease aggressiveness and poor survival. Although these observations implicate NOS2 as an attractive therapeutic target, the mechanisms of both NOS2 induction in tumors and nitric oxide (NO)-driven cancer progression are not fully understood. To enhance ourmechanistic understanding of NOS2 induction in tumors and its role in tumor biology, we used stimulants of NOS2 expression in ER- and ER+ breast cancer cells and examined …

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …

Cytoprotective Versus Non-Protective Autophagy Induced By Radiation In Head And Neck Cancer Cells, Duaa Bakhshwin

Theses and Dissertations

The primary treatment options for head and neck cancer are radiation therapy or surgery, or both combined; chemotherapy is often used as an additional, or adjuvant, treatment. Patients treated with radiotherapy are exposed to a high cumulative dose of radiation over a period of time and there is a 17-33% chance of recurrence. High cumulative doses of radiation, a long time course of treatment, side effects and the possibility of recurrence provide the rationale for developing approaches for radiation sensitization, which could be helpful to patients in decreasing the dose, duration of radiation, side effects, or the chance of recurrence. …

Limited Brain Metabolism Changes Differentiate Between The Progression And Clearance Of Rabies Virus., Keith Schutsky, Carla Portocarrero, D Craig Hooper, Bernhard Dietzschold, Milosz Faber

Department of Microbiology and Immunology Faculty Papers

Central nervous system (CNS) metabolic profiles were examined from rabies virus (RABV)-infected mice that were either mock-treated or received post-exposure treatment (PET) with a single dose of the live recombinant RABV vaccine TriGAS. CNS tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral RNA. Although the large majority of these metabolic changes were completely absent in the brains of TriGAS-treated mice most likely due to the strong reduction in virus spread, TriGAS treatment resulted in the up-regulation of the expression of …

Characterization Of Extraction Methods To Recover Phenolic Rich Extracts From Pinto Beans That Exert High Antioxidative Activities Using Response Surface Approach, Mohammed Aldawsari

Department of Food Science and Technology: Dissertations, Theses, and Student Research

The pinto bean has been linked to the prevention of multiple diseases due in large part to the presence of phenolic antioxidants, which are higher in beans than in many fruits and vegetables. These components deliver health properties beyond basic nutritional characteristics by scavenging free oxygen radicals. However, these benefits are most likely due to the ability of these chemically diverse phenols to impart greater protective properties as additives or synergists acting in combination. However, optimal parameters to isolate these compounds (in terms of ratios and types) from a given natural source are not known. Without this knowledge, understanding the …

Fatty Acids Increase Neuronal Hypertrophy Of Pten Knockdown Neurons, Catherine J. Fricano, Tyrone Despenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary Westbrook, Bryan Luikart

Dartmouth Scholarship

Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy …

The Effect Of Size On Ag Nanosphere Toxicity In Macrophage Cell Models And Lung Epithelial Cell Lines Is Dependent On Particle Dissolution, Raymond F. Hamilton, Sarah Buckingham, Andrij Holian

Biomedical and Pharmaceutical Sciences Faculty Publications

Silver (Ag) nanomaterials are increasingly used in a variety of commercial applications. This study examined the effect of size (20 and 110 nm) and surface stabilization (citrate and PVP coatings) on toxicity, particle uptake and NLRP3 inflammasome activation in a variety of macrophage and epithelial cell lines. The results indicated that smaller Ag (20 nm), regardless of coating, were more toxic in both cell types and most active in the THP-1 macrophages. TEM imaging demonstrated that 20 nm Ag nanospheres dissolved more rapidly than 110 nm Ag nanospheres in acidic phagolysosomes consistent with Ag ion mediated toxicity. In addition, there …