Pharmacology, Toxicology and Environmental Health Commons^™

Hiv-1 Protease Inhibitors From Marine Brown Alga: A Literature Review, Eric Nunez Aguilar

McNair Research Journal SJSU

The human immunodeficiency virus type 1 (HIV-1) causes an infectious disease that if left untreated can progress to acquired immunodeficiency syndrome (AIDS) and be fatal. Finding a cure and more treatments for HIV has become a top priority in medical research, and due to the cost of synthetic HIV medication, finding a low-cost alternative is essential. Marine pharmacology has provided a possible solution to costly HIV medication through compounds derived from marine brown algae that inhibit the HIV-1 protease (PR). The objective of this study is to emphasize the necessity for further research in HIV-1 protease inhibition using marine wildlife-derived …

Using Freshwater Mussels As An Indicator For River Water Quality, Joseph Gerland, Will Titone, Ariana Clark, Brad Michael

Undergraduate Research Conference

Using the freshwater mussel to monitor water quality is a practical and advantageous way to use nature’s indicator species. River water quality is an important measurement that is constantly monitored for many purposes. The sampling involved with monitoring can be very costly and time-consuming. Using mussels as indicator species could save money and time. So, this project has been dedicated to exploring the applications and reality of using freshwater mussels to monitor river quality.

Physiological Effects Of Five Different Marine Natural Organic Matters (Noms) And Three Different Metals (Cu, Pb, Zn) On Early Life Stages Of The Blue Mussel (Mytilus Galloprovincialis), Lygia Sega Nogueira, Adalto Bianchini, Scott Smith, Marianna Basso Jorge, Rachael L. Diamond, Chris M. Wood

Chemistry Faculty Publications

Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis—one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of …

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

Hawkes Co. V. United States Army Corps Of Engineers, Sarah M. Danno

Public Land & Resources Law Review

A peat mining company will not be required to obtain a permit under the Clean Water Act to discharge dredged and fill material into wetlands. The United States District Court for the District of Minnesota held that the United States Army Corps of Engineers fell short in its attempts to establish jurisdiction over the wetlands by twice failing to show a significant nexus existed between the wetlands and navigable waters. Further, the district court enjoined the Corps from asserting jurisdiction a third time because it would force the mining company through a “never ending loop” of administrative law.

Pharmacology, Pharmacokinetics, And Metabolism Of The Dna-Decoy Ayx1 For The Prevention Of Acute And Chronic Post-Surgical Pain, Julien Mamet, Scott Harris, Michael Klukinov, David C. Yeomans, Renee R. Donahue, Bradley K. Taylor, Kelly Eddinger, Tony Yaksh, Donald C. Manning

Physiology Faculty Publications

Background: AYX1 is an unmodified DNA-decoy designed to reduce acute post-surgical pain and its chronification with a single intrathecal dose at the time of surgery. AYX1 inhibits the transcription factor early growth response protein 1, which is transiently induced at the time of injury and triggers gene regulation in the dorsal root ganglia and spinal cord that leads to long-term sensitization and pain. This work characterizes the AYX1 dose-response profile in rats and the link to AYX1 pharmacokinetics and metabolism in the cerebrospinal fluid, dorsal root ganglia, and spinal cord.

Results: The effects of ascending dose-levels of AYX1 on mechanical …

Therapeutic Modulation Of Cancer Metabolism With Dichloroacetate And Metformin, Nathan Patrick Ward

USF Tampa Graduate Theses and Dissertations

The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin’s reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in the VM-M3 model of GBM. We demonstrated that metformin potentiated DCA-induced superoxide production and that this was required for enhanced cytotoxicity towards VM-M3 cells with the combination. Similarly, rotenone enhanced oxidative stress resultant …

The Optimization Of The Nuclear Protein In Testis (Nut) Antibody And Its Importance And Impact In The Pathology Lab, Lindsey Martinez

USF Tampa Graduate Theses and Dissertations

Optimization in immunohistochemistry is often a time consuming and complex process. There are a varying array of moving parts to consider all while preserving the sensitivity and specificity of the test. When optimizing an antibody it is important to consider the fixation of the tissue and the type of epitope retrieval that would be best suited for the test. The dilution of the primary antibody is a key marker for the efficiency and effectiveness of the laboratory protocol. The purpose of this study was to produce an optimized antibody for the nuclear protein in testis to detect NUT midline carcinoma …

Trap-Neuter-Return Programs And The Importance Of Associated Public Awareness, Nicolette Sliwa

Biology: Student Scholarship & Creative Works

The focus of this paper is to describe a typical Trap-Neuter-Return (TNR) program and highlight the major pros and cons surrounding this somewhat controversial method of managing the overwhelming free-roaming cat population. The effects of the species’ overabundance on the environment and human health are also discussed. Citing studies completed on TNR programs around the globe as well as mathematical models, the effectiveness of this method is compared to other, currently used alternatives. Finally, it has been suggested that the general awareness level a neighborhood possesses about the true goals of TNR programs has a potentially significant impact on the …

Utilization And Accessibility Of Securinega Virosa For Medical Use In Morogoro Municipality, Sasha Friedrich

Independent Study Project (ISP) Collection

Approximately 80% of rural communities in Tanzania utilize the services of traditional healers. This is largely because modern medicine is often expensive, inaccessible, or has undesirable side effects. This study investigates use of traditional medicine in Morogoro Urban district where people do have access to hospitals. In particular, this study aims to assess the utilization and accessibility the plant species Securinega virosa for medicinal use by identifying and interviewing the actors involved in the supply chain from harvester to consumer. I conducted semi-structured interviews with eight traditional healers and one herbal medicine shopkeeper. I expected harvesters to express a decline …

A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity, Banrida Wahlang, Jordan T. Perkins, Michael C. Petriello, Jessie B. Hoffman, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the …

Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs, Nathan Puckett

Masters Theses & Specialist Projects

Platinum complex drugs such as cisplatin have been used as highly successful chemotherapy drugs since the 1970s. We are interested in how the ligands attached to cisplatin analogs influences their reactivity with biologically relevant targets along with time and amount. For this study, reactions were conducted to determine the reactivity between different platinum compounds and the protein bovine serum albumin. Various platinum compounds with different ligands were reacted in varying amounts with albumin in ammonium acetate buffer for either 1 hour, 4 hours, or 24 hours. Each reaction was quenched after the designated reaction time by dialysis and the platinum …

Biokinetics Of Nanomaterials: The Role Of Biopersistence, Peter Laux, Christian Riebeling, Andy M. Booth, Joseph D. Brain, Josephine Brunner, Cristina Cerrillo, Otto Creutzenberg, Irina Estrela-Lopis, Thomas Gebel, Gunnar Johanson, Harald Jungnickel, Heiko Kock, Jutta Tentschert, Ahmed Tlili, Andreas Schäffer, Adriënne J. A. M. Sips, Robert A. Yokel, Andreas Luch

Pharmaceutical Sciences Faculty Publications

Nanotechnology risk management strategies and environmental regulations continue to rely on hazard and exposure assessment protocols developed for bulk materials, including larger size particles, while commercial application of nanomaterials (NMs) increases. In order to support and corroborate risk assessment of NMs for workers, consumers, and the environment it is crucial to establish the impact of biopersistence of NMs at realistic doses. In the future, such data will allow a more refined categorization of NMs. Despite many experiments on NM characterization and numerous in vitro and in vivo studies, several questions remain unanswered including the influence of biopersistence on the toxicity …

Thiamine Deficiency Induces Endoplasmic Reticulum Stress And Oxidative Stress In Human Neurons Derived From Induced Pluripotent Stem Cells, Xin Wang, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem …

The Methane-Oxidizing Capability Of Pumice Biocovers On Icelandic Landfills, Mitchell P. Miller

Independent Study Project (ISP) Collection

Pumice has been shown in laboratory biofilter experiments to improve the oxidation of methane (Pratt et al. 2012, Pratt, Tate, & Deslippe 2012). Pumice biocovers were tested on two Icelandic landfills, Kirkjuferjuhjáleiga and Álfsnes. Seven biocover plots were dug and filled with a 50:50 blend of pumice and native soil. CH4 and CO2 were measured using the static chamber method before and after biocover placement. After one week, the CH4:CO2 ratio was reduced on four of the seven plots, weakly indicating that pumice biocovers may be an effective way to better oxidize landfill methane.

Development Of A Wild Infant Woolly Monkey Social Interactions, Time Allocation And Behavior Of A Wild Lagothrix Lagotricha Poeppigii Infant And Her Mother, Saba Zewdie

Independent Study Project (ISP) Collection

The lowland woolly monkey (Lagothrix lagotricha poeppigii), like all species of woolly monkey, is extremely threatened due to anthropologic activities such as deforestation, petroleum drilling and commercial hunting across their habitat. Due to their low reproductive rate and low reproductive success in captivity, the captive population is decreasing every year as habitat loss increases. In late February of 2017 an infant female was born on the island of Sumak Allpa, a monkey rehabilitation organization and reserve in the western Ecuadorian Amazon. The woolly monkeys are completely independent on the reserve; and as such her birth marks the first …

Investigation De Regeneración Natural De Plantas Vasculares En La Reserva Madrigal Del Podocarpus / Investigation Of Natural Regeneration Of Vascular Plants In The Madrigal Reserve Of The Podocarpus, Sy Baker

Independent Study Project (ISP) Collection

En el Sur de Ecuador, hay una historia larga de incendio que está asociada con la historia de la agricultura y ganadería a causa de las técnicas de tala y quema para despejar áreas para campos y también quemaduras intencionales para fertilizar los suelos y mejorar productividad agrícola (Fernandez et al 2015). En los últimos días de Noviembre de 2016, un incendio quemó campos, la Reserva Madrigal de Podocarpus, y parte del Parque Nacional Podocarpus en Loja, Ecuador—el enfoque de este estudio. En este estudio: (1) se registraron las especies y distribución de plantas pioneras y sobrevivientes, (2) la se …

Factors That Determine Civil Action In Opposition To Hydroelectric Development Along The Chiriquí Viejo River In The Chiriquí Province Of Panamá, Nora Sawyer

Independent Study Project (ISP) Collection

Hydroelectric development has increased rapidly throughout Latin America in the late 20th and early 21st centuries (del Mar Rubio et al. 2014). In 2014, Latin America represented 20 percent of the world’s hydropower (del Mar Rubio et al. 2014). It is also the main source of power generation throughout Latin America, accounting for roughly 65 percent of all electricity generated (Wheeler 2012). Within Panamá, significant hydroelectric development has been happening in the Chiriquí province. Local peoples’ dissatisfaction with the actions of the hydropower companies has increased with time, resulting in civilians and organizations taking action in opposition to these companies …

Fish Community Assessment Of The Bonyic And Teribe Rivers Within The Naso-Teribe Territory Bocas Del Toro, Panama: Possible Implications Of Bonyic Dam., Shaylyn Austin

Independent Study Project (ISP) Collection

In the Changuinola/Teribe watershed of Bocas Del Toro, Panama, changes to the fluvial system due to the recently constructed Bonyic Dam have implications connected to the biodiversity of a UNESCO Biosphere Reserve and the livelihoods of thousands of people of the Naso-Teribe indigenous group. This study investigated the composition of fish communities in 6 study sites in 3 different areas in relation to the Bonyic Dam. A total of 318 individual fish were captured, representing 5 families and 10 species, using the cast net sampling method. The biodiversity was analyzed using Simpson’s Diversity Index, Evenness Index, species richness, and species …

Enzyme-Dependent Fluorescence Recovery Of Nadh After Photobleaching To Assess Dehydrogenase Activity Of Isolated Perfused Hearts., Angel Moreno, Sarah Kuzmiak-Glancy, Rafael Jaimes, Matthew W Kay

Pharmacology and Physiology Faculty Publications

Reduction of NAD(+) by dehydrogenase enzymes to form NADH is a key component of cellular metabolism. In cellular preparations and isolated mitochondria suspensions, enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) of NADH has been shown to be an effective approach for measuring the rate of NADH production to assess dehydrogenase enzyme activity. Our objective was to demonstrate how dehydrogenase activity could be assessed within the myocardium of perfused hearts using NADH ED-FRAP. This was accomplished using a combination of high intensity UV pulses to photobleach epicardial NADH. Replenishment of epicardial NADH fluorescence was then imaged using low intensity UV illumination. NADH …

Proteome Dynamics During Postnatal Mouse Corpus Callosum Development., Alexander I Son, Xiaoqin Fu, Fumikazu Suto, Judy S Liu, Kazue Hashimoto-Torii, Masaaki Torii

Pharmacology and Physiology Faculty Publications

Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled …

Role Of Cytokines And Chemokines In Alcohol-Induced Tumor Promotion, Danlei Chen, Fengyun Zhang, Haifeng Ren, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines …

A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats., Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee

Pharmacology and Physiology Faculty Publications

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes …

Mammary Epithelial Polarity And Macrophage Infiltration, Ren Xu

Pharmacology and Nutritional Sciences Faculty Publications

Loss of epithelial cell polarity and inflammation are hallmarks of breast cancer development. Although the association between the disruption of tissue polarity and inflammation has been demonstrated, we know little about how these two events are coupled. Using the 3D co-culture model of mammary epithelial cells and monocytes, a recent study reveals a link between disruption of epithelial polarity and monocytes infiltration.

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency, Thomas Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, David Mendelowitz, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6–8 weeks genioglossus EMG and dynamic MRI …

Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia, P Steullet, J Cabungcal, J Coyle, M Didriksen, K Gill, Anthony-Samuel Lamantia, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant …

Trash Removal Methods For Improved Mechanical Emptying Of Pit Latrines Using A Screw Auger., Tracey Sisco, Tate Rogers, Walt Beckwith, Willy Chipeta, Rochelle Holm, Christopher A. Buckley, Francis L. De Los Reyes

Faculty and Staff Scholarship

Trash in pit latrines is one of the largest challenges facing pit emptying technologies, including the powered auger (the Excrevator), developed for improved emptying in lower- and lower-middle income countries. This study focused on two trash removal methods in conjunction with pit emptying by the Excrevator: (1) simultaneous removal of trash with sludge and (2) manual trash removal prior to sludge removal. Simultaneous removal was tested by adding to the inlet of the Excrevator system two cutting heads designed to reduce the size of trash particles before entering the pipe and auger. Laboratory testing indicated that the auger will not …

An Open-Sourced Statistical Application For Identifying Complex Toxicological Interactions Of Environmental Pollutants, Jordan T. Perkins, Michael C. Petriello, Li Xu, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

The rising number of chemicals that humans are exposed to on a daily basis, as well as advances in biomonitoring and detection technologies have highlighted the diversity of individual exposure profiles (complex body burdens). To address this, the toxicological sciences have begun to shift away from examining toxic agents or stressors individually to focusing on more complex models with multiple agents or stressors present. Literature on interactions between chemicals is fairly limited in comparison with dose-response studies on individual toxicants, which is largely due to experimental and statistical challenges. Experimental designs capable of identifying these complex interactions are often avoided …

Mechanisms Of Thymic Toxicity Induced By Environmentally Relevant Concentrations Of Arsenic, Huan Xu

Biomedical Sciences ETDs

Arsenic, a ubiquitous environmental contaminant, is known to cause immunotoxicity. However, the mechanisms of arsenic induced immunotoxicity are still not clear. Arsenite (As⁺³), the trivalent inorganic form of arsenic, was found to increase DNA damage and inhibit PARP activity in thymus cells at 50 nM in vitro. Oxidative stress and double strand breaks (DSBs) formation occurred in thymus cells exposed to As⁺³ at 500 nM. The genotoxicity was found to be related to As⁺³ exporter expressions and reversed by zinc supplement. IL-7 signaling, the critical cytokine signal for the early DN thymic T cell proliferation, …