Pharmacology, Toxicology and Environmental Health Commons^™

Applying A Novel Systems Approach To Address Systemic Environmental Injustices: Constructing Soil For Limiting The Legacy Of Lead (Pb), Sara Perl Egendorf, Peter M. Groffman, Zhongqi Cheng, Michael Menser, Jan Mun, Howard Mielke

Advanced Science Research Center

The knowledge of unsustainable human and Earth system interactions is widespread, especially in light of systemic environmental injustices. Systems science has enabled complex and rigorous understandings of human and Earth system dynamics, particularly relating to pollution of Earth’s land, water, air, and organisms. Given that many of these systems are not functioning sustainably or optimally, how might this field enable both rigorous understanding of the issues and experiments aimed at alternative outcomes? Here, we put forth a novel, multiscale systems science approach with three steps: (1) understanding the systemic issues at hand, (2) identifying systemic interventions, and (3) applying experiments …

Comparative Studies On Biochemical And Pharmacological Profiles Of Unfractionated Heparins & Their Depolymerized Derivatives From Bovine, Ovine And Porcine Origins, Ahmed Kouta

Dissertations

Heparin and heparin related drugs have remained the anticoagulant of choice for medical and surgical indications. These drugs are comprised of poly-component sulfated chains of varying length and biophysical structure with direct and indirect pharmacological effects. Heparins produce their therapeutic effects by multiple mechanisms involving both the cellular and humoral targets. These drugs represent natural products which are isolated from mammalian tissue rich in mast cells. Currently used heparin and LMWHs are obtained from porcine mucosal tissue. Other animal sources including bovine and ovine tissues also provide additional sources for the manufacturing of heparins. While there may be microchemical and …

Cardioprotective Extracellular Vesicles Derived-Micrornas: Sorting Mechanisms And Functions, Anh P. Phan

Dissertations

Extracellular vesicles (EVs) are nano-size membrane bound vesicles that are derived from the fusion of multivesicular endosomes with the plasma membranes. EVs have important roles in intercellular communication through the transfer of their unique cargoes including RNA, DNA and protein molecules to recipient cells. Mesenchymal stem cell (MSC)-derived EVs have been shown to reduce infarct size and reduce the progress of heart failure after cardiac ischemia/reperfusion (I/R) injury in animal models. Small non-coding RNAs such as microRNA (miRNA) have been indicated as one of the active components that mediate the beneficial effects of MSC-derived EVs. However, the selective packaging mechanisms …

Elucidation Of Multi-Origin Inula Helenium L. For Antimicrobial Activity And Heavy Metal Profiling As An Exemplar For The Use And Regulation Of Plants As Antibiotics., Ciara Ruth Kenny

Theses

An impending post-antibiotic era looms, thus new sources of therapeutic chemical entities are crucial to sustain effective antimicrobial chemotherapy worldwide. Plant natural products are a source of accessible, structurally diverse compounds that provide therapeutic potential. The pharmacological applications of plants in medicine can be guided by the attestation of traditional use or the application of this knowledge to uncover new leads in the drug discovery process. The range of modified in vitro methods commonly used to investigate preclinical antimicrobial efficacy of plant-derived natural products, and the associated limitations and challenges in the provision of new antimicrobial drugs from plants is …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

The Cb1 Receptor Positive Allosteric Modulator, Zcz011, Attenuates Naloxone-Precipitated Withdrawal Signs In Oxycodone-Dependent Mice And Inhibits Small Intestinal Transit In Mice, Julien Dodu

Theses and Dissertations

The endogenous cannabinoid system tightly regulates a myriad of physiological and pathophysiological functions. Effects of cannabinoids in ameliorating opioid withdrawal signs has been known for decades. Naloxone precipitates several withdrawal signs (e.g., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid dependent rodents. ∆⁹-tetrahydrocannabinol (THC) has been shown to ameliorate opioid withdrawal in mice through the activation of cannabinoid type-1 (CB₁) receptors. Inhibition of the endocannabinoid degradative enzymes also attenuates these withdrawal signs (i.e., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid-dependent mice. Specifically, inhibition of fatty acid amide hydrolase (FAAH), …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Great East Lake 2021 Water Quality Highlight Report, Amanda Mcquaid, Robert Craycraft

UNH Cooperative Extension

A Water Quality Highlight Report by UNH CE Lakes Lay Monitoring Program for Great East Lake (Wakefield, NH; Acton , ME) for sampling efforts in 2021.

Belleau Lake 2021 Water Quality Highlight Report, Amanda Mcquaid, Robert Craycraft

UNH Cooperative Extension

A Water Quality Highlight Report by UNH CE Lakes Lay Monitoring Program for Belleau Lake in Wakefield, NH for 2021.

Influence Of 2,5-Dimethoxy-4-Iodoamphetamine (Doi) On Ethanol Preference And Consumption In C57bl/6 Male Mice, Alaina M. Jaster, Sam Gottlieb, Michael Miles, Javier González-Maeso

Graduate Research Posters

Substance use disorders (SUD) account for a large number of mental health diagnosis in the United States and around the world. Approximately 13.6 million adults 26 or older and 5.1 million young adults (ages 18-24) battled with a SUD in 2017. Alcohol Use Disorder (AUD) alone effects nearly 6% of the adult population within the United States. This creates a substantial burden on the individual, with alcohol being the third-leading cause of preventable death in the United States. Few treatments for AUD exist, with no new FDA-approved therapeutic treatments within the last 15 years. Additionally, the limited treatments we do …

A Temporal Record Of Microplastic Pollution In Mediterranean Seagrass Soils, Martin Dahl, Sanne Bergman, Mats Björk, Elena Diaz-Almela, Maria Granberg, Martin Gullström, Carmen Leiva-Dueñas, Kerstin Magnusson, Candela Marco-Méndez, Nerea Piñeiro-Juncal, Miguel Ángel Mateo

Research outputs 2014 to 2021

© 2021 Elsevier Ltd Plastic pollution is emerging as a potential threat to the marine environment. In the current study, we selected seagrass meadows, known to efficiently trap organic and inorganic particles, to investigate the concentrations and dynamics of microplastics in their soil. We assessed microplastic contamination and accumulation in 210Pb dated soil cores collected in Posidonia oceanica meadows at three locations along the Spanish Mediterranean coast, with two sites located in the Almería region (Agua Amarga and Roquetas) and one at Cabrera Island (Santa Maria). Almería is known for its intense agricultural industry with 30 000 ha of plastic-covered …

High Throughput Analysis To Study Emerging Pollutants And Nanoparticle Fate In Biological Systems, Xiaolong He

Doctoral Dissertations

”The increasing applications of emerging and fugitive contaminants (EFCs) and engineered nanoparticles (ENPs) attract significant research interest for their potential risks to human health and the environment. In order to assess the health risks of these emerging contaminants, rapid and reliable analytical methods to measure the concentrations and fates of these contaminants are imperative. This dissertation focuses on the developments of advanced analytical methods and their applications to study those emerging contaminants in crop plant and simulated gastric fluid (SGF). Three types of mass spectrometry based methodologies have been developed, one is freeze-thaw/centrifugation extraction followed by high performance liquid chromatography …

Seaweed Polysaccharide In Food Contact Materials (Active Packaging, Intelligent Packaging, Edible Films, And Coatings), Kalpani Perera, Shubham Sharma, Dileswar Pradhan, Amit Jaiswal, Swarna Jaiswal

Articles

Food contact materials (FCMs) are materials that come in contact with food products such as food packaging which play a significant role in food quality and safety. Plastic, which is a major food packaging material, harms the ecosystem, wildlife, and the environment. As a result, numerous researches have been in progress on alternative polymers, which have similar properties as plastic but are also environmentally friendly (biodegradable). In recent years, the utilization of seaweed polysaccharides has piqued interest due to their biodegradability, non-toxicity, antioxidant capabilities, and excellent film formation ability. However, it has a number of drawbacks such as low tensile …

Structure Based Prediction Of A Novel Gpr120 Antagonist Based On Pharmacophore Screening And Molecular Dynamics Simulations, Ajay Pal Mr, Gemma K. Kinsella, James Curtin

Articles

The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. Recent implications of its role in cancer progression have presented GPR120 as an attractive oncogenic drug target. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. Some agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. …

The Effects Of Fluoride On Macrophage Thp-1 Cell Apoptosis, Jessica Heims

Honors Program Theses

Fluoride is an earthly mineral that occurs naturally both in the sedimentary earth as well as in the human body. The main biological function of fluoride in the human body is to enhance bone structure, as well as prevent the decay of teeth. This mineral has been used by dentists and public health officials to artificially introduce an extra layer of protection through the means of fluoride-enriched public water supplies and toothpastes. By using extra levels of fluoride, dentists have been able to help patients prevent future cavities and dental diseases. Although most dentists highly encourage strategic consumption of these …

Full Issue: Volume 14, Number 2, Spring 2021

The Science Journal of the Lander College of Arts and Sciences

Complete .pdf file of Volume 14, Number 2 of The Science Journal of the Lander College of Arts and Sciences. Published Spring 2021.

The Relationship Between Autoimmunity And Polyautoimmunity, David Schon

The Science Journal of the Lander College of Arts and Sciences

Autoimmune disease refers to a systemic immune response by the body against its own healthy tissue and cells. This results in various non-specific and systemic inflammatory processes that evolve into more than 100 individual diseases. Numerous biological similarities exist between the different pathophysiological pathways, including biochemical cascades and inflammasome mediators. This paper aims to investigate whether contracting one form of autoimmune disease can lead to the development of polyautoimmunity and multiple autoimmune syndrome. Scientists have identified chronic levels of high stress as a contributor to higher levels of C-reactive protein and several immune modulating interleukins, which can lead to both …

What Are The Possible Causes And Effective Therapeutic Approaches Of Preeclampsia?, Adina Hadi

The Science Journal of the Lander College of Arts and Sciences

Preeclampsia is a complication of pregnancy primarily characterized by hypertension and proteinuria and affects other organs as well. The underlying causes are not yet fully understood. However, it is suggested that angiogenic factors of the placenta, genetic factors, a malfunctioning immune system, and oxidative stress all play a role in causing preeclampsia. Currently, the only definitive cure known for preeclampsia is delivery of the baby. Management of the condition includes taking preventative measures as well as drugs such as labetalol and MgSO4. This paper analyzes mechanisms of preeclampsia and determines the possible causes and most effective ways to manage the …

Effects Of Soy Isoflavone, Anne Roberts

The Science Journal of the Lander College of Arts and Sciences

Soy, which contains a form of phytoestrogen known as isoflavones, impacts the biological activity of humans at all stages. There are many aspects to consider when determining whether soy is beneficial. Since the hormone estrogen plays a significant role in maintaining the biochemical and homeostatic conditions of an individual, it follows that the disruption of estrogenic levels can be detrimental. There are many hormone- dependent diseases that can be linked to one’s diet, and the possibility of utilizing phytoestrogens, such as soy, to prevent or control hormonal irregularities is compelling. This paper explores the effects that phytoestrogens, specifically soy, can …

Migraine Triggers, Adina Jeidel

The Science Journal of the Lander College of Arts and Sciences

Migraines are a painful and life-interrupting disease which strikes around 23 million Americans every year (Goadsby et al., 2017). Not enough studies have been done to help the public fully understand migraines. Details regarding the causes and pathophysiology of migraines continue to be analyzed by physicians and scientists, as no theory has been fully confirmed regarding a migraine’s concrete path. The goal of this scientific review is to provide an overview for the main triggers of migraines, in reference to recent clinical investigations, and to understand why they might cause patients to be more prone to having a migraine attack …

Rapamycin And Metformin In Treating Covid-19, Avrohom Karp

The Science Journal of the Lander College of Arts and Sciences

The SARS-CoV-2 virus has spread rapidly, resulting in a global pandemic. There is a great need for an effective drug cocktail therapy to combat Acute Respiratory Distress Syndrome (ARDS), a major cause of death due to COVID-19. The two drugs examined are metformin, an antidiabetic medication, and rapamycin. Rapamycin is often prescribed for transplant patients as it has an immunosuppressive effect. The aim of the investigation was to determine the efficacy of metformin and rapamycin in treating COVID-19, and to examine what an effective protocol would look like. These two drugs both inhibit mTOR and can reduce the body’s auto-immune …

Developing Approaches Towards The Treatment Of Covid-19, Chana Weis

The Science Journal of the Lander College of Arts and Sciences

In late 2019 a newly identified strain of coronavirus, SARS-CoV-2 emerged, causing a worldwide pandemic of respiratory illness, Covid-19. Covid-19 has drastically transformed the world in numerous ways. The virus is highly contagious and, in some cases, fatal. A successful cure has not yet been discovered and therefore society is urged to take proper precautions to prevent the spread of the potentially fatal virus. This paper analyzes the proper precautions that should be taken as well as the ongoing research that has been done to stop the spread of the virus.

Full Issue: Volume 15, Number 1, Fall 2021

The Science Journal of the Lander College of Arts and Sciences

Complete .pdf file of Volume 15, Number 1 of The Science Journal of the Lander College of Arts and Sciences. Published Fall 2021.

Understanding The Potential Of Plasma Activated Liquids For Biomedical Applications, Evanthia Tsoukou

Doctoral

Atmospheric cold plasma has evolved as a new technology for applications used in biomedicine, agriculture and food industry. Recently, treatment of liquids using various atmospheric pressure plasmas has attracted much attention owing to multiple practical applications such as water purification, surface cleaning and decontamination with impact in dentistry, wound healing and sterilisation, or cancer therapy. The over-arching aim of this study is to build a better understanding of the parameters which govern the liquid chemistry generated in a liquid exposed to cold plasma and how these translate into biological effects on pro- and eu-karyotic organisms. The objective was to investigate …

Retrospective Review Of Pharmacogenetic Testing At An Academic Children's Hospital., Timothy A. Roberts, Jennifer A. Wagner, Tracy L. Sandritter, Benjamin T. Black, Andrea Gaedigk, Stephani L. Stancil

Manuscripts, Articles, Book Chapters and Other Papers

There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic children's hospital to determine the potential utility of PGx in diseases of childhood and to identify targets for future pediatric pharmacogenetic research. An actionable gene-drug pair associated with the 28 genes tested (Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B, Pharmacogenomics Knowledge Base (PharmGKB) level 1A or B, or US Food and Drug Administration (FDA) recommendation and a PharmGKB level) was present in 98.7% of patients. We identified 203 actionable gene-drug-diagnosis groups based on …

Determining The Effects Of Imidacloprid On Non-Target Soil Organisms In Hemlock Stands, Braley Burke

Graduate Theses, Dissertations, and Problem Reports (ETD)

The hemlock woolly adelgid (HWA), Adelges tsugae Annand (Hemiptera: Adelgidae), is an invasive insect that is causing mortality of eastern hemlock trees, Tsuga canadensis, and Carolina hemlock trees, Tsuga caroliniana, across the eastern United States. To protect these ecologically important tree species, a neonicotinoid insecticide, imidacloprid, is commonly used. Imidacloprid is an effective treatment and can remain effective against HWA for four to six years but long-term (≥ one year after application) non-target effects of imidacloprid on forest ecosystems are not well-studied. This study examined terrestrial non-target effects of imidacloprid in hemlock stands with different treatment histories to …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …