Pharmacology, Toxicology and Environmental Health Commons^™

How Do The Social Benefits And Costs Of The Patent System Stack Up In Pharmaceuticals?, Daniel J. Gifford

Georgia Journal of Law & Technology

This paper explores the workings of the patent system in the context of the generation of new pharmaceutical products. First it identifies the relevant characteristics of the patent system and its relation to the market. The paper concedes that, in general, the patent system is probably the best way of generating new technology, in substantial part because that system uses the market to provide both incentives and rewards. The paper also identifies downsides of this patent/market system: deadweight loss and the unresponsiveness of that patent/market system to the needs of the poor. The paper then explores the social costs and …

X-Ray Fluorescence For Quantification Of Lead And Strontium In Vivo, Aaron James Specht

Open Access Dissertations

Lead (Pb) is a toxicant well known for its effects on almost every organ system in the body. Pb use in industry has declined since removal of Pb from gasoline, but many developing countries still have significant use of Pb. Exposure to Pb has been linked with diseases causing neurodegeneration and thus have lasting effects long after the initial exposure. Another metal, strontium (Sr), has been linked with bone disease in particular situations and shown to have uses in treating osteoporosis as a supplement. However, there are no studies of the effects of Sr using a meaningful biomarker. The most …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Investigation Of The Tailoring Steps In Pradimicin Biosynthesis, Kandy L. Napan

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This research focused on the investigation of the late steps in the biosynthetic pathway of the novel antifungal and antiviral pradimicins A-C. Pradimicins were first isolated from the soil bacterium Actinomadura hibisca. These bioactive molecules are assembled by a type II polyketide biosynthetic pathway. Although the biosynthetic gene cluster of pradimicin has been identified, the functions of the biosynthetic genes and how they work collaboratively to form the final structures of pradimicins remain unknown. This research aims to functionally characterize the enzymes involved in the late steps of the biosynthetic route.

The early biosynthetic steps of pradimicins have been …

Novel Approaches For Assessment Of Copper Toxicity: Fast Scan Cyclic Voltammetry And Optical Bioassays, Annette R. Tremonti

Wayne State University Dissertations

Anthropogenic activities negatively impact fresh water ecosystems through toxic contaminants that are released into the environment. Copper (Cu) is a water contaminant that is fundamentally persistent once introduced into the environment that has the potential for bioaccumulation. Although Cu toxicity has been studied for decades, there is still a continuing problem with new sources and pathways. New approaches are needed to understand distribution and transport of Cu and its potential for complex biological impacts beyond the simple assessment of lethality. Several novel approaches were used in this research project to advance our understanding of Cu toxicity, including fast scan cyclic …

Lifetime And Effectiveness Evaluation Of Ceramic Pot Filters, Carlo Salvinelli

Doctoral Dissertations

"Poor water quality is a major contributing factor to disease in developing countries. Ceramic pot filters (CPFs) represent an effective and sustainable technology for poor communities, but the characterization of CPF lifetimes is on-going, and the water production seems to be the limiting factor. This dissertation describes laboratory and field investigations conducted to characterize the parameters that impact CPF effectiveness and lifetime in terms of water production and treatment efficacy, both under controlled and real use conditions.

CPF initial flow rate is the most common quality control parameter, but it may not be representative of the long-term effectiveness of the …

Targeted Delivery Of Nrf2 Sirna Using Modular Polymeric Micellar Nanodelivery System For Efficient Target Gene Knockdown In Hepatocellular Carcinoma, Shaimaa Mohamed Ibrahim Yousef

Wayne State University Theses

Tumor selective drug delivery as well as chemotherapy associated multi drug resistance (MDR) pose tremendous hurdles for effective cancer therapy. In this regard, designing multifunctional nanocarriers loaded with drug/gene payloads and engineered with tumor targeting ligands can serve as a modular platform for targeted drug/gene delivery. In this study we undertook the synthesis of a self-assembling block copolymer constructed using poly(styrene-co-maleic anhydride, partial iso-octyl ester) (SMAPIE) and branched polyethylenimine (PEI) as building blocks and evaluated its micelle forming ability, siRNA complexation and siRNA delivery potentials. In addition, we engineered galactosamine decorated nanomicelles using modular “click” chemistry based approaches for evaluating …

Artificial Neural Network Approach To Predict Blast-Induced Ground Vibration, Airblast And Rock Fragmentation, Raymond Ninnang Tiile

Masters Theses

"Blasting has been widely used as an economical and cheap way of rock breakage in mining and civil engineering applications. An optimal blast yields the best fragmentation in a safe, economic and environmentally friendly manner. The degree of fragmentation is vital as it determines to a large extent the utilization of equipment, productivity and mill throughput. Explosive energy, besides rock fragmentation, creates health and safety issues such as ground vibration, air blast, fly rock, and back breaks among others. As a result, the explosive energy impacts structures and buildings located in the vicinity of the blasting operation, and causes human …

Assessing Public Health Burden Associated With Exposure To Ambient Black Carbon In The United States, Ying Li, Daven K. Henze, Darby Jack, Barron H. Henderson, Patrick L. Kinney

ETSU Faculty Works

Black carbon (BC) is a significant component of fine particulate matter (PM_2.5) air pollution, which has been linked to a series of adverse health effects, in particular premature mortality. Recent scientific research indicates that BC also plays an important role in climate change. Therefore, controlling black carbon emissions provides an opportunity for a double dividend. This study quantifies the national burden of mortality and morbidity attributable to exposure to ambient BC in the United States (US). We use GEOS–Chem, a global 3-D model of atmospheric composition to estimate the 2010 annual average BC levels at 0.5 x 0.667° …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …

Eicosapentaenoic Acid (Epa) From Porphyridium Cruentum: Increasing Growth And Productivity Of The Microalgae For Pharmaceutical Products, Maryam Asgharpour

Graduate Theses and Dissertations

One of the major nutritional requirements in our diet is an adequate intake of omega-3 specially eicosapentaenoic acid (EPA). In the present study, the effects of two temperatures (16°C & 20˚C) and light intensities (140 & 180µE/M2.S) and four nitrate levels (0.075, 0.3, 0.5 and 0.7g/L) on the cell growth and lipid productivity of Porphyridium cruentum, one of the most promising oil-rich species of microalgae, were investigated. A growth comparison was carried out using pure CO2 and 5% CO2/air. Additionally, the ratio of the fatty acids with omega-3 and omega-6 groups at various growth conditions were compared, since an appropriate …

Photocatalytic Mineralization Of Phenol On Fluidized Titanium Oxide-Coated Silica Gel, Guillermo J. Rincon

LSU New Orleans Theses and Dissertations

A bench-scale tubular reactor with recirculation was built in order to study the efficiency of the photocatalytic oxidation of phenol on fluidized titanium oxide-coated silica gel beads. A UV-C lamp placed along the central vertical axes of the reactor was used as source of photons. A bed of silica gel beads was fluidized by means of fluid recirculation and forced to follow upward helical flow around the lamp. Anatase was successfully synthetized on silica gel particles of average diameters 224, 357 and 461 µm, as confirmed by scanning electron micrographs, through a sol-gel technique using a titanium (iv)isopropoxide / hydrochloric …

An Evaluation Of Carbon Concentrations Associated With Biodiesel Particulate Matter In An Underground Metal Mine, David Evans

Graduate Theses & Non-Theses

Exposure to diesel particulate matter from diesel exhaust has been shown to have adverse health effects in humans. In 2012 The International Agency for Research on Cancer classified diesel exhaust as a group 1 know human carcinogen. Because of the associated health effects, there has been a strong push to reduce the amount of diesel exhaust present in the mining industry. Biodiesel is one to the more common and promising control options used to reduce the amount of diesel particulate matter that is generated during fuel combustion. The use of biodiesel over petroleum diesel has been shown to reduce not …

Concomitant Uptake Of Antimicrobials And Salmonella In Soil And Into Lettuce Following Wastewater Irrigation, J. Brett Sallach, Yuping Zhang, Laurie Hodges, Daniel D. Snow, Xu Li, Shannon L. Bartelt-Hunt

Department of Civil and Environmental Engineering: Faculty Publications

The use of wastewater for irrigation may introduce antimicrobials and human pathogens into the food supply through vegetative uptake. The objective of this study was to investigate the uptake of three antimicrobials and Salmonella in two lettuce cultivars. After repeated subirrigation with synthetic wastewater, lettuce leaves and soil were collected at three sequential harvests. The internalization frequency of Salmonella in lettuce was low. A soil horizon-influenced Salmonella concentration gradient was determined with concentrations in bottom soil 2 log CFU/g higher than in top soil. Lincomycin and sulfamethoxazole were recovered from lettuce leaves at concentrations as high as 822 ng/g and …

Characterization Of Metallic And Semimetallic Oxide Nanoparticles In Industrial Wastewater And Associated Toxicity, Gary Roth

Legacy Theses & Dissertations (2009 - 2024)

Engineered nanomaterials (ENMs) play an increasing role in manufacturing and consumer products. Currently, there is no standard approach to studying ENM toxicity, and a growing body of literature suggests that ENMs may have toxicity differing from similar compounds in bulk or dissolved form. I examined ENMs used in the semiconductor manufacturing process called chemical-mechanical planarization (CMP) for their properties, removal in the wastewater treatment system (WWT), in-vitro toxicity, and location post-inhalation in-vivo. It was found that ENMs in CMP slurries have morphology determined by their elemental composition, but assessment of size and concentration can differ substantially between accepted techniques. Particles …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Detecting Diesel Particulate Matter Using Real Time Monitoring Under The Influence Of An Exhaust Fan System, Yasir Helal Alghamdi

Masters Theses

"Diesel Particulate Matter (DPM) is a complex mixture of diesel exhaust gas that consists of carbon, ash, metallic abrasion particles, sulfates and silicates. The diesel soot particle includes a solid core made of elemental carbon, and organic carbon compound attached to the surface of the soot particle. The main source of DPM is diesel exhaust gas. The National Institute for Occupational Safety and Health (NIOSH) and the Environmental Protection Agency (EPA) have determined that DPM is the source of most of the emissions of carbon monoxide, carbon dioxide, oxide of nitrogen, and hydrocarbons in underground coal, metal and non metal …

Integrated Nanoscale Imaging And Spatial Recognition Of Biomolecules On Surfaces, Congzhou Wang

Theses and Dissertations

Biomolecules on cell surfaces play critical roles in diverse biological and physiological processes. However, conventional bulk scale techniques are unable to clarify the density and distribution of specific biomolecules in situ on single, living cell surfaces at the micro or nanoscale. In this work, a single cell analysis technique based on Atomic Force Microscopy (AFM) is developed to spatially identify biomolecules and characterize nanomechanical properties on single cell surfaces. The unique advantage of these AFM-based techniques lies in the ability to operate in situ (in a non-destructive fashion) and in real time, under physiological conditions or controlled micro-environments.

First, AFM-based …

Development And Characterization Of An Autologous Whole Cell Breast Cancer Vaccine, Samantha Leigh Kurtz

Graduate Theses and Dissertations

Approximately 40,000 women will die from breast cancer in the United States in 2014. About 90% of these deaths will be due to metastases, rather than the primary tumor and majority of metastases are due to the recurrence and progression of non-metastatic disease. Current adjuvant treatments, such as chemotherapy and radiation, have severe side effects and may result in overtreatment and drug resistance.

Since greater than 90% of patients are diagnosed between stages I-III and have minimal residual disease after treatment, there is an opportunity to treat patients with an autologous breast cancer vaccine. Autologous vaccines under development have a …

Role Of Group Ii Metabotropic Glutamate Receptor Subtype 2 (Mglur2) In Appetitive And Consummatory Aspects Of Ethanol Reinforcement, Kyle Allyson Windisch

Open Access Dissertations

Background: Group II metabotropic glutamate receptors (mGluR2/3) are predominately presynaptically located G_i/o coupled receptors that are highly expressed in the cortex, nucleus accumbens, amygdala, and hippocampus. Previous studies suggest that group II mGluRs are involved in regulating ethanol (EtOH) consumption and seeking following extinction (Backstrom and Hyytia, 2005; Kufahl, et al., 2011). The sipper tube model, which allows for procedural separation of seeking and consumption, was used to further clarify the role of mGluR2/3 in EtOH-seeking and consumption. The non-selective group II mGluR agonist LY379268 (LY37) and selective mGluR2 positive allosteric modulator (PAM) BINA were used to determine the …

Health Risks Caused By Wireless Technologies, Durreeshahwar Zafarahmed, Qurrat-Ul-Ain Zafarahmed

Journal of Undergraduate Research at Minnesota State University, Mankato

There are many health issues related to the use of cellular phones, wireless local area networks, and other devices that emit electromagnetic radiation (EMR). Some of these systems have become a part of our daily lives and many of us are in direct or indirect contact for extended period of times with these devices. However, the general public is unaware of the health risks associated with the use of these devices. Our research covers studies done by individuals as well as organizations on the harmful effects on the health of people from these devices and their claims. We also present …

Tissue Engineering: Applications In Developmental Toxicology, Stephanie N. Thiede, Nimisha Bajaj, Kevin Buno, Sherry L. Voytik-Harbin

The Summer Undergraduate Research Fellowship (SURF) Symposium

In vivo toxicology assays are expensive, low-throughput, and often not predictive of a human response. Three-dimensional in vitro human cell-based tissue systems incorporating cell-cell and cell-matrix interactions have promise to provide high-throughput, physiologically-relevant information on the mechanism of the toxin and a more accurate assessment of the toxicity of a chemical before progression to human trials. Quantification of the disruption of vasculogenesis, the de novo formation of blood vessels from endothelial progenitor cells, can serve as an appropriate indicator of developmental toxicity since vasculogenesis is critical to the early development of the circulatory system. The current routinely used in vitro …

Affluent Populations And Their Effect On Biological Diversity Through The Consumption Of Meat, Electronics, And Motor Vehicles, Melody Flores

Honors College Theses

The human has caused a far greater impact on the planet's biodiversity than any other species in existence, due to the impact of population, afflluence, and technology. This thesis will argue the importance of biological diversity and how affluent populations are reducing biodiversity through the consumption of meat, electronics, and motor vehicles. Aldo Leopold's "The Land Ethic" and Herman Daly's "The Impossibility Theorem", among others, create a rubric evaluating human activities and provide alternative views on economic impossibilities. Consumption is reviewed from an ecocentric perspective, a holistic outlook placing emphasis on the ecosystem. The reader will become cognizant of their …

Design Of Functional Dendrimer Nanocarriers And Their Formulations In Propellant-Based Inhalers For Pulmonary Drug Delivery, Lin Yang

Wayne State University Dissertations

This Dissertation focuses on addressing two of the major challenges in developing pressurized metered dose inhalers for pulmonary drug / gene delivery to and through the lungs. First challenge is to design biocompatible moieties for the steric stabilization of suspension formulations in HFO-based propellants. Using a combination of tools including ab initio calculation, molecular dynamics simulation and high pressure tensiometry, potential fluorocarbon-philic moieties were systematically screened. Surfactants with those chemistries as tail fragments were studied at the HFO|H2O interface for their ability to lower the interfacial tension at HFO|H2O interface. Selected surfactants were further optimized for surfactant balance by altering …

Exposure Assessment And Risk Management Of Engineered Nanoparticles : Investigation In Semiconductor Wafer Processing, Michele Shepard

Legacy Theses & Dissertations (2009 - 2024)

Engineered nanomaterials (ENMs) are currently used in hundreds of commercial products and industrial processes, with more applications being investigated. Nanomaterials have unique properties that differ from bulk materials. While these properties may enable technological advancements, the potential risks of ENMs to people and the environment are not yet fully understood. Certain low solubility nanoparticles are more toxic than their bulk material, such that existing occupational exposure limits may not be sufficiently protective for workers. Risk assessments are currently challenging due to gaps in data on the numerous emerging materials and applications as well as method uncertainties and limitations.

Dual Delivery Systems Based On Polyamine Analog Benspm As Prodrug And Gene Delivery Vectors, Yu Zhu

Wayne State University Dissertations

Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range …

Addressing Public Health Risks Of Persistent Pollutants Through Nutritional Modulation And Biomimetic Nanocomposite Remediation Platforms, Bradley J. Newsome

Theses and Dissertations--Chemistry

Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) pose significant health risks and enduring remediation challenges. Engineered nanoparticles (NPs) provide a novel platform for sensing/remediation of these toxicants, in addition to the growing use of NPs in many industrial and biomedical applications, but there remains concern for their potential long-term health effects. Research highlighted herein also represents a transdisciplinary approach to address human health challenges associated with exposure to PCBs and NPs. The objectives of this dissertation research are two-fold, 1) to develop effective methods for capture/sensing and remediation …

Non-Mass Transfer Limited Crystal Growth, Ryan J. Smyth, Caitlin Schram, Stephen P. Beaudoin

The Summer Undergraduate Research Fellowship (SURF) Symposium

There are many different active pharmaceutical ingredients (APIs) that have been discovered in research labs all around the world that can be used to treat and cure patients with a variety of different ailments. The challenge with these APIs in treatments is that they are not soluble in water, thus they low absorption into the blood stream (bio-availability). The key to making these APIs more bio-available is to understand how they grow as crystals and drop out of the aqueous solutions. One of the ways these APIs were made more bio-available is to render them amorphous and suspend them in …

Juxtaposing Nasa’S Aeronet Aod With Carb Pm Data Over The San Joaquin Valley To Facilitate Multi-Angle Imaging Spectroradiometer (Misr) Pm Pollution Research, John Kanemoto

STAR Program Research Presentations

Airborne particulate matter (PM) has been shown to increase the risk for asthma, chronic bronchitis, cardiopulmonary complications, and respiratory cell membrane damage/infection/leakage. PM levels are currently analyzed from two perspectives: stationary land-based monitoring (LBM) sites and total Aerosol Optical Depth (AOD) atmospheric column measurements. Both perspectives often leave miles of space between measuring locations and will have a continually increasing cost from introducing/maintaining sites. The Multi-angle Imaging SpectroRadiometer (MISR) satellite team hopes to begin investigating/archiving PM levels comprehensively via inputting MISR AOD measurements into a function/model which predicts the amount of ground level PM.

In the future, multivariable spatial correlations …

Polymeric Nanocarriers And Their Oral Inhalation Formulations For The Regional Delivery Of Nucleic Acids To The Lungs, Denise Santos Conti

Wayne State University Dissertations

Gene therapy has attracted attention in the fields of medicine, pharmacy, and bionanotechnology due to the potential for treating a large number of medically relevant diseases. Oral inhalation (OI) is a promising route for the administration of therapeutics, including small molecules and biomacromolecules, such as nucleotides, peptides, and proteins, to (locally) and through (systemically) the lungs. The use of OI is especially attractive for the delivery of nucleic acids as it provides a direct and non-invasive route for targeting the lungs. Pressurized metered-dose inhalers (pMDIs), are the most commonly used OI in treatment of lung diseases and are thus promising …