Pharmacology, Toxicology and Environmental Health Commons^™

Proton Pump Inhibitors Use In Short Bowel Patients At A Thai Tertiary Hospital: A 10-Year Retrospective Observational Study, Sasisom Phadungkingtrakul, Namthip Iamkaeo, Piyathida Isutsiri, Prattana Sirisupamongkhon, Suyanee Pongthananikorn, Tippawan Siritientong

The Thai Journal of Pharmaceutical Sciences

Background: Proton pump inhibitors (PPIs) reduce the gastric acid secretion in short bowel patients. However, the absorptive areas of these patients are limited. In case of residual jejunum length <50 cm, the intravenous administration of PPIs should be .

Sex Differences In The Mechanisms That Modulate The Neurochemical Effects Of Nicotine, Kevin Uribe

Open Access Theses & Dissertations

Prior behavioral studies in our laboratory revealed that overexpression of the stress peptide, corticotrophin-releasing factor (CRF), in the mesocorticolimbic reward pathway enhanced the reinforcing effects of nicotine. The latter effect was greater in female versus male rats, suggesting that females are uniquely susceptible to the effects of stress on nicotine reinforcement. The goal of this dissertation was to examine the neurochemical mechanisms by which overexpression of CRF in the nucleus accumbens (NAc), a terminal region of the mesocorticolimbic pathway, modulates the behavioral effects of nicotine. Specifically, we examined whether nicotine-induced dopamine levels are altered by CRF overexpression via excitatory (glutamate) …

The Effect Of Waterpipe/Hookah On Platelet Function And The Impact Of Inhibition Of Gβγ Subunits On Hemostasis And Thrombogenesis, Ahmed Alarabi

Open Access Theses & Dissertations

Abstract (Hookah)

Cardiovascular diseases (CVD’s) is a major public health problem. Among CVD’s risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of CVD’s mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipe/hookah has been rising, mainly due to the perception that they are “less harmful” than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. We employed a waterpipe whole-body exposure protocol that mimics real‐life human …

In-Vitro Localisation And Degradation Of Few-Layer Mos2 Submicrometric Plates In Human Macrophage-Like Cells: A Label Free Raman Micro-Spectroscopic Study, Caroline Moore, Andrew Hrvey, Jonathan N. Coleman, Hugh Byrne, Jennifer Mcintyre

Articles

Monitoring the uptake, micro-environment and fate of micro or nano scaled particulate materials in cells is of paramount importance for the emerging fields of toxicology and medicine. Such particulate materials are known to interfere with colorimetric assays and many such assays record only a single end-point. Therefore, there is a need for a label-free, cost effective technique with little or no inference from the particulate materials. Raman micro-spectroscopy was used to simultaneously interrogate the integrity of few-layer MoS2 submicrometric plates in human macrophage-like cells, in-vitro, as well as the biochemical characteristics of the local micro-environment in which they are encompassed. …

Reducing Reperfusion Injury In An Adult Rat Stroke Model With St-115 Treatment, Morgan Rae Lenz

Master's Theses

The restoration of blood flow to ischemic cerebral tissue can result in reperfusion injury, and blocking reperfusion injury can significantly aid in recovery of ischemic tissue. Bradykinin has been shown to exhibit protective effects, but does not reach protective levels during reperfusion due to inactivation by aminopeptidase P2 (APP2). Therefore, inhibiting APP2 during reperfusion is a potential therapeutic strategy to aid in the reduction of reperfusion injury, leading to the development of ST-115, an APP2 inhibitor. It was hypothesized that administration of ST-115 during ischemic stroke, and just prior to reperfusion, will result in reduced neurological injury and increased functional …

Phytochemical Screening, In Vitro Antimalarial Activity And Genetic Diversity Of Selected Asteraceae Medicinal Plants Indigenous To Thailand, Desy Liana

Chulalongkorn University Theses and Dissertations (Chula ETD)

The emergence of artemisinin resistance leaded the effort to find the new antimalarial drug or artemisinin activity booster. Due to the chance that secondary metabolites can be evolutionary conserved, combining phylogeny with ethnobotanical data for screening antimalarial activity may be helpful to predict bioactivity and minimize the expenditure and time for laboratory research. The aimed of this study is screening the antimalarial activity, phytochemicals and genetic diversity of selected Asteraceae medicinal plants generated by combinatorial phylogeny and ethnobotanical data. 733 medicinal plants were obtained from literature search however only 340 taxa were met the inclusion and exclusion criteria hence these …

Pharmacology Of Fentanyl-Related Substances In Mice Reveals Potential Therapeutics With Improved Protective Indices, Neil B. Varshneya

Theses and Dissertations

Fentanyl-related substances constitute a class of compounds that were originally developed in the latter half of the 20th century as combination analgesic-anesthetic agents. Today, many of these compounds have emerged in the recreational drug marketplace as adulterants to heroin, counterfeit prescription pills, and even as standalone products designed to circumvent drug control laws. The objective of this dissertation was to identify the structural determinants of fentanyl analogs that could affect the potency and efficacy for eliciting their therapeutic and toxic effects to identify candidates of potential therapeutic interest. To accomplish this objective, thirty-eight fentanyl-related substances, in addition to the MOR …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …

Exosomes As Systemic Mediators Of Nanotube Induced Neurotoxicity, Christopher G. Canal

Theses and Dissertations

Extra-pulmonary effects of nanoparticle inhalation have been well documented; however, mechanisms for conveying peripheral bioactivity remain elusive. Recent studies point to indirect molecular mediators shed into the circulation. Protein and lipid alternatives to cytokines or chemokines have been proposed, yet the diversity among responses suggests a broader assemblage of factors. Recently we have proposed proteolytic fragment peptides as an additional source of bioactivity, which interestingly were significantly associated with exosomal proteins after enrichment analysis. Here we tested whether modeled exposure to multi-walled carbon nanotubes (MWCNT) could alter the composition and bioactivity of circulating exosomes. Male C57BL/6 mice were exposed by …

Ailing In Place: Environmental Inequities And Health Disparities In Appalachia, Michele Morrone

Ohio University Press Open Access Books

In Ailing in Place, Michele Morrone explores the relationship between environmental conditions in Appalachia and health outcomes that are too often ascribed to individual choices only. She applies quantitative data to observations from environmental health professionals to frame the ways in which the environment, as a social determinant of health, leads to health disparities in Appalachian communities. These examples—these stories of place—trace the impacts of water quality, waste disposal, and natural resource extraction on the health and quality of life of Appalachian people.

Public health is inextricably linked to place. Environmental conditions such as contaminated water, unsafe food, and polluted …

Characterization Of Cardiovascular Risk Factors People Living With Hiv In A Veteran Population, Veronica Taylor, Joe Castillo, Daniel Tassone Pharmd, Bcps

Graduate Research Posters

Background: CVD is the leading cause of death in PLWH. HIV positive individuals have a 1.5-2-fold greater risk of CVD compared to uninfected individuals, even if complete viral load suppression is achieved. HIV-associated CVD has tripled over the past 20 years, yet scant data is available describing this population. We have characterized CVD risk factors and treatment in PLWH in order to assess and improve cardioprotective treatment.

Methods: A retrospective EMR review was conducted for HIV positive patients enrolled at the McGuire VAMC between 12/2018 and 12/2019. Patients were excluded if labs were older than one year from follow-up. …

Evaluation Of Wound Healing Potential, Antioxidant Activity, Acute Toxicity And Gastro Protective Effect Of 2-Pentadecanone In Ethanol Induced Gastric Mucosal Ulceration In Rats, Kamran Sareh

Student Works (2020-2029)

Wound is an injury to normal tissue that can happen either externally or internally such as wound in skin tissue or stomach tissue. Compound 2-pentadecanone a ketone derivative, has been identified in some plants, and was reported to have anti-bacterial, antioxidant and anti-inflammatory activities. The aim of this study was to evaluate skin wound healing and gastro-protective potential effect of 2-pentadecanone in Sprague dawley rats. Acute toxicity assay was performed to detect safety of 2-pentadecanone. In the evaluation of skin wound healing, dorsal neck of rats were induced wounds and topically treated with 2-pentadecanone for 10 days. Meanwhile, for gastroprotective …

Data Mining Raman Microspectroscopic Responses Of Cells To Drugs In Vitro Using Multivariate Curve Resolution-Alternating Least Squares, David Perezguaita, Guillermo Quintas, Zeineb Farhane, Roma Tauler, Hugh Byrne

Articles

Raman microspectroscopy is gaining popularity for the analysis of time-dependent biological processes such as drug uptake and cellular response. It is a label-free technique which acquires signals from a large variety of components, including cell biomolecules and exogenous compounds such as drugs and nanoparticles, and is commonly employed for in vitro analysis of cells and cell populations with no labelling or staining required. By monitoring the changes to the Raman spectra of the cell as a result of a perturbing agent (e.g. exposure to a drug or toxic agent), one can study the associated changes in cell biochemistry involved in …

Potential Of Raman Spectroscopy For The Analysis Of Plasma/Serum In The Liquid State: Recent Advances, Drishya Rajan Parachalil, Jennifer Mcintyre, Hugh Byrne

Articles

There is compelling evidence in the literature to support the application of Raman spectroscopy for analysis of bodily fluids in their native liquid state. Naturally, the strategies described in the literature for Raman spectroscopic analysis of liquid samples have advantages and disadvantages. Herein, recent advances in the analysis of plasma/serum in the liquid state are reviewed. The potential advantages of Raman analysis in the liquid form over the commonly employed infrared absorption analysis in the dried droplet form are initially highlighted. Improvements in measurement protocols based on inverted microscopic geometries, clinically adaptable substrates, data preprocessing and analysis, and applications for …

Atr-Ir Spectroscopy For Rapid Quantification Of Water Content In Deep Eutectic Solvents, Suha Elderderi, Charlotte Leman-Loubiére, Laura Wills, Sandra Henry, Dominique Bertrand, Hugh Byrne, Igor Chourpa, Cécile Enguehard-Gueiffier, Emilie Munnier, Abdalla A. Elbashir, Leslie Boudesocque-Delaye, Franck Bonnier

Articles

Natural Deep Eutectic solvents (NADES) are green, ionic solutions prepared by mixing vegetal cellular constituents. They are renewable and biodegradable solvents composed of hydrogen bonded donor and acceptor compounds. NADES have a wide range of applications, mainly as solvents for extraction of plants, biocatalysis, and nanoparticle synthesis. Water content is very critical, impacting significantly on NADES properties. Therefore, controlling H2O concentration appears essential for optimal use of NADES. In the present study, Attenuated Total Reflectance – infrared spectroscopy (ATR-IR) coupled to multivariate analysis, namely Partial Least Square s regression (PLSR), was investigated as a rapid, label free and cost-effective tool …

The Combined Effects Of Chemicals Used In Textile Processing On Plankton Communities., Diana Wilson

Honors College Theses

Industrial discharge, such as textile effluent, is a major source of chemical mixtures to surface waters. The effects of these mixtures on interacting aquatic organisms can be difficult to predict. We hypothesized that individual chemical effects on phytoplankton and a zooplankton grazer are altered by the presence of other chemicals in mixtures. Microcosms containing a phytoplankton food source (Chlorella sp.) and a zooplankton grazer (Daphnia magna) were exposed to THPC, ammonium, and hydrogen peroxide in a fully crossed design in a greenhouse for one week. Phytoplankton abundance was quantified and zooplankton response was measured as mortality and …

Surfacant Contamination Alters Freshwater Phytoplankton Community Composition, William H. Hodge

College of Graduate Studies: Theses & Dissertations

Pollution from cleaning and personal care products enter freshwater systems and have the potential to alter phytoplankton abundance and diversity. Alkyl polyglucoside (APG), a widely used foaming agent in detergents, decreases phytoplankton abundance, but whether sensitivity to APG is affected by taxonomic identity and/or the presence of competitors is unclear. Establishing taxon-specific responses to APG is important, because taxa differ in nutritional quality and palatability for zooplankton grazers.

Chapter one describes comparisons between how individual phytoplankton communities respond to the same range of APG concentrations to test hypotheses that: 1) chemical concentration determines how individual taxa respond to APG; 2) …

What The Covid-19 Crisis Is Telling Humanity, David Wiebers, Valery Feigin

Animal Sentience

The planet is in a global health emergency exacting enormous medical and economic tolls. It is imperative for us as a society and species to focus and reflect deeply upon what this and other related human health crises are telling us about our role in these increasingly frequent events and about what we can do to prevent them in the future.

Cause: It is human behavior that is responsible for the vast majority of zoonotic diseases that jump the species barrier from animals to humans: (1) hunting, capture, and sale of wild animals for human consumption, particularly in live-animal markets; …

New Approach To Health And The Environment To Avoid Future Pandemics, Serge Morand

Animal Sentience

This commentary expands Wiebers & Feigin’s target article by pinpointing how declining wildlife, expanding livestock and globalisation contribute to the increase in epidemics of zoonotic diseases, the COVID-19 crisis and future health crises. Epidemics and the emergence of zoonoses are manifestations of dysfunctional links with animals, both wild and domestic, requiring a new approach to health and the environment.

Structural Features Of 1,3,4-Thiadiazole-Derived Ligands And Their Zn(Ii) And Cu(Ii) Complexes Which Demonstrate Synergistic Antibacterial Effects With Kanamycin, Dariusz Karcz, Arkadiusz Matwijczuk, Daniel Kaminski, Bernadette Creaven, Katarzyna Lecka-Szlachta, Karolina Starzak

Articles

Classical synthetic protocols were applied for the isolation of three novel 1,3,4-thiadiazole derivatives which were then complexed with the biologically important Cu(II) and Zn(II) ions. All free ligands and their corresponding complexes were characterized using a number of spectroscopic techniques including Ultraviolet-visible (UV–vis), Fluorescence, Infrared (FT-IR), tandem liquid chromatography-mass (LC-MS), X-ray diffraction (XRD), and Nuclear Magnetic Resonance (NMR) spectroscopy (¹H, ¹³C, HSQC, HMBC). The results obtained are consistent with the formation of dihydrate complexes, in which the chelation of the metal ion occurs via one of the thiadiazole nitrogen atoms and the deprotonated hydroxyl group of the …

Treating Anemia Of Chronic Disease, Sarit Fischer

The Science Journal of the Lander College of Arts and Sciences

Anemia of chronic disease (ACD) is the result of altered iron metabolism, blunted erythropoiesis, and shortened red blood cell survival caused by inflammatory cytokines. Hepcidin plays a key role in anemia of chronic disease by inducing endocytosis of the iron exporter ferroportin. Iron is trapped in enterocytes, hepatocytes, and macrophages, and is unavailable for hemoglobin synthesis. When treating the underlying disease is not an option, or anemia is severe, ACD should be treated. While oral iron supplementation is not suitable for ACD, intravenous iron may be effective. Erythropoiesis stimulating agents are a common approach to treating ACD, but a large …

Full Issue: Volume 14, Number 1, Fall 2020

The Science Journal of the Lander College of Arts and Sciences

Complete .pdf file of Volume 14, number 1 of The Science Journal of the Lander College of Arts and Sciences. Published Fall 2020.

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry …

In Vitro Assessment Of Deleterious Impacts Of Organomodified Nanoclays And Their Incinerated Byproducts On Human Cells, Andrew Philip White

Graduate Theses, Dissertations, and Problem Reports (ETD)

Organomodified nanoclays (ONCs: i.e., smectite clays with different organic coatings), act as nanofillers in applications ranging from automotive, to aerospace, and biomedical implementations. Because of their large utilization, ONC industry is projected to be a U.S. $3.3 billion industry by 2023. However, emerging studies showed that ONCs and ONC-nanocomposites could harbor health risks upon pulmonary exposure and along their life cycle, namely during synthesis, handling, use, manipulation, and disposal. Specifically, the potential for exposure and adverse effects on human health primarily includes release of dry particulate during handling, manipulation, release during use, and release during the end-of-life disposal or recycling …

Pulmonary Immune Responses To Respirable Elongate Mineral Particles Of Asbestiform And Non-Asbestiform Morphologies, Timur Khaliullin

Graduate Theses, Dissertations, and Problem Reports (ETD)

Inhalation exposure to asbestiform elongate mineral particles (EMPs) may cause pulmonary fibrosis, lung and pleural cancer. At the same time, epidemiological evidence for non-asbestiform EMP pathogenicity is scarce, with little if any risk of cancer, but consistent findings of pneumoconiosis and increased mortality. Globally, conditions caused by asbestos exposures contribute most to the occupational cancer burden and are responsible for the increasing mortality for occupational respiratory diseases. Immunological components of the fiber-induced lesions are extremely understudied, partly due to the lack of comparable test articles. In this study I utilized respirable preparations of asbestiform and non-asbestiform riebeckite and tremolite to …

Distribution And Evolution Of Fukushima Dai-Ichi Derived 137cs, 90sr, And 129i In Surface Seawater Off The Coast Of Japan, Jennifer A. Kenyon, Ken O. Buesseler, Núria Casacuberta, Maxi Castrillejo, Shigeyoshi Otosaka, Pere Masqué, Jessica A. Drysdale, Steven M. Pike, Virginie Sanial

Research outputs 2014 to 2021

© 2020 American Chemical Society. The Fukushima Dai-ichi Nuclear Power Plants (FDNPPs) accident in 2011 led to an unprecedented release of radionuclides into the environment. Particularly important are 90Sr and 137Cs due to their known health detriments and long half-lives (T1/2 ≈ 30 y) relative to ecological systems. These radionuclides can be combined with the longer-lived 129I (T1/2 = 15.7 My) to trace hydrologic, atmospheric, oceanic, and geochemical processes. This study seeks to evaluate 137Cs, 90Sr, and 129I concentrations in seawater off the coast of Japan, reconcile the sources of contaminated waters, and assess the application of 137Cs/90Sr, 129I/137Cs, and …

Phytoremediation Potential Of Four Heavy Metals In Soil By Chromolaena Odorata (L.) King & Robinson At The Phytotoxicity Screening Benchmarks, Gloria O. Omoregie, Beckley Ikhajiagbe, Geoffery O. Anoliefo

Tanzania Journal of Science

The remediative capacity of Chromolaena odorata with respect to heavy metal induced growth-stress was investigated. This was with a view to providing information on the adaptive mechanisms adopted by the test plant during the phytoremediation of selected heavy metals such as copper, manganese, zinc and cadmium. Stems of C. odorata were planted in soils polluted with  Mn, Zn, Cd, and Cu at the ecological screening benchmark (ESB) of 50 mg/kg (Mn and Zn), 4 mg/kg (Cd) and 100 mg/kg (Cu) of metal per kilogram of soil, in varying concentrations of 0 ESB (control), 1 ESB, 3 ESB and 5 ESB. …

There Must Be Something In The Water: Understanding Pfas Contamination Of Groundwater As A National Security Issue, Kylie N. Ford

Student Theses 2015-Present

This report addresses the widespread pollution of domestic groundwater resources with Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) caused by firefighting activities performed at military installations across the United States. Two former military bases in Southeastern Pennsylvania are used as a single case study: the Naval Air Development Center (NADC) in Warminster and the Naval Air Station Joint Reserve Base (NASJRB) in Horsham. Chapter 1 gives a history of domestic military bases from the perspective of the infrastructure buildup and downsizing that occurred over the 20th Century, along with the environmental degradation revealed during brownfield redevelopment. The chapter then gives specifics about …

Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng

Theses & Dissertations

Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …