Pharmacology, Toxicology and Environmental Health Commons^™

Pharmacogenomic Biomarkers Of Angiotensin Converting Enzyme Inhibitors (Aceis) Induced Cough Among Healthy Emiratis And Multi-Ethnic Hypertensive Patients, Sahar Mohammad Altoum

Theses

Pharmacogenomics (PGx) is an emerging field that merges genetics with pharmacology. It focuses on how an individual's genetic makeup influences their response to specific medications. This relatively new area of medicine seeks to understand the genetic factors that affect drug efficacy and safety. One practical application of PGx is in the context of treatment with angiotensin-converting enzyme inhibitors (ACEIs), which are widely used medications for managing hypertension. However, ACEIs are often associated with cough as a side effect, leading to drug discontinuation and the adoption of alternative medications like Angiotensin II receptor blockers (ARBs). The prevalence of ACEIs-induced cough varies …

The Interaction Of Sodium Fluoride And Sodium Selenate On The Developmental Toxicity To Xenopus Laevis And Ambystoma Maculatum Embryos, Shelby Wolfram

Theses

Amphibians play critical roles in the environment's wellness. Fluoride (F) is a widely existing environmental pollutant. It is commonly known for being added to drinking water and as a topical dose on teeth. Selenium (Se) can be found in organic and inorganic forms in nature. Many different fertilizers, pesticides, insecticides, and fungicides contain sodium selenate in them. The range selenium has between deficiency and toxicity is narrow, meaning excess exposure could cause various adverse effects in aquatic organisms. Xenopus laevis is a standard model for developmental toxicity due to being minimal maintenance, cost efficient, and having transparent embryos. Xenopus makes …

New Treatment Modality For Metastatic Cancer By Targeting The Endothelin Type A Receptor (Etar), Elbara Fathelrahman Abdelmoula

Theses

Ambrisentan, an FDA-approved selective antagonist of the Endothelin Type A Receptor (ETAR) for pulmonary arterial hypertension, has shown potential in limiting cancer growth and metastasis. While effective treatment options for melanoma remain elusive, this study investigates the effects of Ambrisentan on invasive, metastatic B16F10 melanoma using a syngeneic mouse model, aiming to assess Ambrisentan’s impact on tumor growth, metastasis, and overall host survival in B16F10 melanoma, along with gaining mechanistic insights into ETAR antagonism. C57Bl/6 mice were divided into two groups, receiving either dH2O or Ambrisentan orally. Treatments commenced prior to tumor implantation and continued post-implantation. Luciferase-expressing B16F10 cells facilitated …

An Exploration Of The Causes And Effects Of Interpersonal Conflict Related Stress Among A Self-Selected Cohort Of Second Level Teachers In Ireland, Patrick Bruce

Theses

Teaching has been classified by researchers as a high stress profession. Stress in teaching has been reported to have many negative health outcomes and also affects productivity. The literature also reports that stress in teaching is a difficult matter to resolve satisfactorily, with mixed outcomes from interventions. An emergent cause of work-related stress in education is IPC and this study sets out to investigate the prevalence of this underreported phenomena.

A sample of 25 teachers working in Irish second level schools were recruited. Semi structured interviews were conducted to report on the experiences of stress, it’s causes and effects both …

Critical Corridor: Survey Of Predator Occurrence And Habitat Use In A Threatened Rainforest Protected Area: Comatsa-Sud And Marojejy National Park, Madagascar, Patrick H. Ross

Theses

Madagascar is a nation praised for its floral and faunal endemism and biodiversity. Among the island nation’s most emblematic fauna are its native mammalian carnivores; they are members of the threatened and endemic Eupleridae family. The Corridor of Marojejy – Anjanaharibe Sud – Tsaratanana (COMATSA) is a system of forest protected areas in which three large protected areas are connected in northern Madagascar: Tsaratanana Reserve, Anjanaharibe Sud Special Reserve and Marojejy National Park which is also a UNESCO World Heritage site. COMATSA is a newly protected and currently threatened corridor system that lacks detailed surveys and assessments of its native …

A Detailed Parameter Study Into The Dermal Absorption Of Chemical Warfare Agents And The Effects Of Pharmacokinetics, Koko Lear

Theses

Chemical warfare agents (CWAs) are substances of varying toxicity profiles. These chemicals exhibit complex dynamics and pose a serious health risk when released into the environment. A mathematical model based on Fick’s second law of diffusion was developed to comprehend how these compounds were absorbed into the skin. The analysis applied to both small and large doses and, successfully, predicted experimental results. This work also includes the effects of CWA physicochemical properties on evaporation and dermal absorption through the stratum corneum. A sensitivity analysis was conducted to assess the impacts of small variations in the initial dose, environmental conditions, and …

The Synthesis And Biological Assessment Of Novel Ursolic Acid Derivatives As Potential Chemotherapeutic Agents For Cancer, Julie Rose Mae Mondala

Theses

Glioblastoma (GBM) is considered to be the most biologically aggressive type of brain tumour accounting for approximately 48% of all malignant primary brain tumours. GBM patients diagnosed have poor prognosis with a low five-year survival rate of

The aim of this study was to develop novel UA derivatives to enhance its bioavailability. Nine novel UA derivatives: three different diamine linkers, with Boc-protected and deprotected ends, and with folic acid were designed and synthesized to improve compound activity and/or delivery. The structures of the newly synthesised compounds were confirmed using mass spectrometry, FTIR, 1H NMR and 13C NMR. The structural activity …

Impact Of Sodium Dichloroacetate Alone And In Combination Therapies On Lung Tumor Growth And Metastasis, Aya Mudhafar A. Al-Azawi

Theses

Lung cancer is the second most common form of cancer with the highest mortality rate worldwide in 2020 despite the advances in targeted- and immuno-therapies. Metabolic reprogramming has been recognized as an essential emerging cancer hallmark in which altered metabolic pathways represent an attractive therapeutic target. Sodium Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, effect has been investigated in various tumors. Building on the already published data, this pre-clinical study aims to explore the anticancer potential of DCA in lung cancer alone and in combination with chemo- and targeted therapies using two non-small cell lung cancer (NSCLC) cell lines …

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 …

Anticonvulsant And Procognitive Properties Of Novel Histamine H3 Receptor Antagonists In Male Adult Rats, Ali Kassem Saad

Theses

To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic and procognitive drugs, aromatic ether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced seizure models in male adult rats having phenytoin (PHT) and valproic acid (VPA) as the reference antiepileptic drugs, pitolisant (PIT) as the standard H3R antagonist/inverse agonist, and donepezil (DOZ) as a reference procognitive drug. Among the H3R ligands (1-12) tested in the current project, H3R …

Biological And Physiological Condition Of Juvenile California Halibut (Paralichthys Californicus) Exposed To A Contamination Gradient In Mission Bay, Ca, Kevin Stolzenbach

Theses

Contaminated sediments in marine environments have been shown to be good indicators of ecological risk and a means to assess anthropogenic impacts on marine habitats and the animals that inhabit them (Long et al. 1995, Rattner 2009). Estuarine sediments are especially complex media with regard to physical, chemical, and biological characteristics that trap, store, modify and sometimes release contaminants to the biota (Long et al. 1995). Especially vulnerable are animals that are in constant contact with the sediments, such as flatfishes that partially bury themselves for camouflage (Costa et al. 2011). Impacts can be assessed in a number of ways, …

The Development Of Liquid Chromatography Mass Spectrometry Methods For The Analysis Of Cyanobacterial Toxins In Environmental Freshwaters, Brian Anthony Dineen

Theses

Cyanobacteria, also known as blue-green algae, are a common component of many freshwater and marine ecosystems and have a potential to produce several different classes of biotoxins. The most common class of cyanobacterial toxins are the microcystins (MCs) and cylindrospermopsins (CYLs). MCs are cyclic heptapeptides that display potent hepatotoxicity and are tumour promoters. CYLs are alkaloids that are cytotoxic and can cause illness and display hepatotoxic effects in animals and humans. Worldwide, these toxins have caused fatal poisonings to animals, birds and fish. Several incidents of human intoxications have been reported and the presence of these toxins in environmental waters …

Investigation Of Pyrrolizidine Alkaloids In Foods Using Liquid Chromatography Mass Spectrometry, Caroline Griffin

Theses

Pyrrolizidine Alkaloids (PAs) are known plant toxins which can cause hepatic veno-occlusive disease (HVOD) in both humans and livestock when ingested. Although PAs are primarily known for their hepatotoxicity they also induce genotoxicity, carcinogenicity and pneumotoxicity. PAs are consumed through plants as food, for medicinal purposes, or as contaminants of agricultural crops. Aside from ingesting the plants directly PA exposure may occur through the consumption of honey produced by bees that visit PA-containing plants or by drinking milk produced by animals that have consumed PA-containing plants. Possible PA contamination in our food chain is a potential health risk.

To assess …

Novel Liquid Chromatography - Fourier Transform Mass Spectrometry (Ms) And Triple Quadrupole Ms Methods For The Determination Of Diarrhetic Shellfish Poisoning (Dsp) Toxins., Bébhine Carey

Theses

Harmful algal blooms (HABs) appear to be on the rise globally, which not only has a negative impact on the shellfish industry but can also cause human and animal intoxications. In order to advance our knowledge of HABs, specific and sensitive analytical methods are required to aid in monitoring shellfish and algal samples for biotoxins, harmful to consumers.

Characterisation Of Pharmaceutical Grade Horse Chestnut Waste, Joanna Przyborska

Theses

Horse chestnut residue was made available by a local pharmaceutical company. The residue was subjected to compositional analysis and studied to determine potential for residual biological activity, including prebiotic, antimicrobial, anti-hyaluronidase and anti-elastase effects.

The residue had 52 % total solids, including 2.97% ash, 6.93% protein, 1.89% crude fat. Oleic acid (74.7%) was the main fatty acid components in the crude lipid component. The major ash components were potassium, phosphorus, calcium and magnesium.

Prebiotic potential of aqueous extract (HCE) from horse chestnut residue was confirmed. A new formula for calculation of prebiotic index (PI) was developed. PI for probiotics (Lactobacillus …

High Resolution Hybrid Mass Spectrometry For The Determination Of Marine Biotoxins, Azaspiracids, And Their Biotransformation Products., Zuzana Skrabakova

Theses

Azaspiracids (AZAs), polyether marine toxins, are produced by marine microalgae and accumulate in filter-feeding bivalve molluscs, such as mussels, clams, oysters and scallops, while grazing on phytoplankton, from which they derive nutrition. Although being discovered quite recently, AZAs have caused several human intoxication events and thus became a problem for health authorities and shellfish industries. The rapid development of highly sensitive liquid chromatography multiple tandem mass spectrometry (LC-MS/MS, LC-MS") methods enabled the identification of numerous AZA analogues and added to the control of shellfish contamination. Tandem mass spectrometry techniques, while being highly selective and sensitive for determination of AZAs in …

Toxicodynamics And Biotransformation Of Azaspiracids Incorporating Liquid Chromatography-Tandem-Mass Spectrometry (Lc-Ms/Ms) Techniques., Daniel O'Driscoll

Theses

Azaspiracids (AZAs) are a family of lipophilic polyether marine biotoxins, that have caused a number of human intoxication incidents in Europe since 1995, which was the first incident reported following the consumption by consumers of intoxicated shellfish {Mytilus edulis). This class of phycotoxins has been responsible for extended closures of shellfisheries in various locations around Europe, where levels of AZAl-3 are regulated in shellfish. Since their discovery in 1995, AZAs have become the focus of extensive research, resulting in the discovery of numerous analogues. Only AZAl and AZA2 have been found in phytoplankton and all the other analogues are believed …

Application Of Multiple Mass Spectrometric Techniques In The Isolation, Determination And Characterisation Of The Marine Toxins; Azaspiracid, Keith O'Callaghan

Theses

The Azaspiracids are a class of polyether marine biotoxins that present a significant health risk to consumers of shellfish. Since their discovery in the late 1990s several human intoxications have been reported, and traced to Irish shellfish farms resulting in closures or harvest rejections. As such incidents involving azaspiracid shellfish poisoning have a major socio-economic impact on communities that rely on shellfish farming revenues.

Recent evidence suggests that azaspiracid poisoning events may become more commonplace. With this increased risk the understanding of azaspiracids mode of action and biological targets becomes crucial. To support these endeavours effective analytical methods need to …

Analytical And Synthetic Methods For Anatoxins., Janet Crowley

Theses

This thesis is focused on the potent cyanobacterial neurotoxins anatoxin-a (AN), its methyl analogue homoanatoxin-a (HMAN) and their non-toxic dihydro- and epoxydegradation products. In commencing the investigation into this area a literature review was performed in order to identify areas where more research and method development was required (Chapter 1). The review highlighted the fact that although a number of analytical methods had been developed for the analysis of AN, there were few methods for the determination of its potent homologue HMAN and their non-toxic degradation products. As these neurotoxins degrade quickly it is important to monitor their degradation products, …

Exploring Marine Biotoxins Using Analytical Techniques Based On Mass Spectrometry, Mónica Fernández Amandi

Theses

The impact of phycotoxins on human and animal health is of important concern for worldwide authorities and the scientific community. Domoic acid (DA) is a neurotoxin produced by phytoplankton {Pseudonitzchia spp.). It enters the food chain through the consumption of shellfish that feed on toxic diatoms. DA has been responsible for several outbreaks affecting humans and animals all around the world. Yessotoxin (YTX) is produced by dinoflagellate species {Protoceratiuni reticulatum) which are globally distributed. Its toxicity is low when ingested orally. However, the co-extraction of YTX with diarrhetic shellfish poisoning (DSP) toxins, derives false positives when the mouse bioassay is …

The Diarrheic Shellfish Poisoning Toxins In Marine Environment Determined Using Liquid Chromatography - Mass Spectrometry Techniques, Patricia Fernández Puente

Theses

A highly specific and sensitive LC-MS/MS analytical method was developed and validated using gradient reversed phase liquid chromatography-tandem mass spectrometry (LC- MS/MS), interfaced using turbo-assisted electrospray ionisation (ESI) in negative mode for the analysis of DSP (okadaic acid (OA), dinophysistoxins (DTXs) and pectenotoxins (PTXs)) toxins in a variety of samples. There were no matrix effects present, proved by the good reproducibility achieved and the linearity of the calibration curves (r" > 0.999) in spiked mussel samples and standards. A DSP toxin profile study was conducted with bulk phytoplankton and mussels samples from the west coast of Ireland. All the samples were …

Analysis Of Phycotoxin And Mycotoxin, Contaminants In Foods, Using Liquid Chromatography - Mass Spectrometry Techniques, Ana Brana Magdalena

Theses

The impact of phycotoxins and mycotoxins on human and animal health are of important concern for worldwide authorities and the scientific community. Liquid chromatography-mass spectrometry (LC-MS) techniques have been developed, optimised and validated for the analysis of these toxins.

Phycotoxins are potentially toxic substances, which are produced by marine phytoplankton and which may accumulate in shellfish or finfish. Azaspiracid poisoning (AZP) is a recently discovered syndrome that has been implicated in several incidents of human intoxications. A study was undertaken to examine the distribution of azaspiracids (AZA) in scallops {Pecten maximiis) and mussels {Mytiliis edulis). Domoic acid (DA) is an …

New Polyether Toxins From Shellfish And Marine Phytoplankton: Isolation Studies And Development Of Analytical Methods, Alan G. Bishop

Theses

There are three classes of polyether toxins responsible for Diarrhetic Shellfish Poisoning (DSP) world-wide. The causative toxins are okadaic acid (OA) and derivatives (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). The origin of these toxins are phytoplankton from Dinophysis or Prorocentrum spp. OA has been demonstrated for most outbreaks in Europe and more recently a new isomer DTX-2 has been reported in Ireland.

Marine phytoplankton biomass samples consisting predominantly of Dinophysis acuta, were acquired using a large double plankton net from waters off the South-west coast of Ireland. Analysis of unialgal samples using high performance liquid chromatography (HPLC) with fluorescence and …

Acidic Marine Biotoxins Implicated In Diarrhetic Shellfish Poisoning, Eoin P. Carmody

Theses

An okadaic acid (OA) etiology has been demonstrated for most outbreaks of diarrhetic shellfish poisoning (DSP) in Europe, An isomer of OA, dinophysistoxin-2 (DTX-2), has recently been found in Irish waters and, in 1991 and 1994, was the major toxin during prolonged infestations in cultivated mussels (Mytilus edulis) along the south-west coast of Ireland.

The OA class of DSP toxins have been analysed by HPLC using modified versions of three established fluorescent derivatisation methods. A ‘dual tag’ method for the confirmation of specific toxins has also been developed.

Survey work has been carried out over the past four years on …

Gas Chromatographic Method For Determination Of 28 Volatile Organic Compounds Emitted From A Sewerage Plant, Yeming Sun

Theses

In this study, 28 volatile organic compounds (VOCs) emitted from the Linden Roselle Sewerage Authority Plant (LRSA) were monitered. The determination by gas chromatography (GC) is presented. This work emphasizes the collection of whole air samples, using a canister-based sampling system with cryogenic concentration. An appropriate temperature program was selected to obtain the best sample separation. The procedure for the identification of 28 standard gas mixture was achieved by comparing the chromatograms of sample with those of the specific groups of target compounds, as well as by comparing the sample with the results from GC Mass spectrometeric analysis. Because of …

Stabilization/Solidification Of Organic Containing Wastes Using Organophilic Clay And Coal Fly Ash, Edith Lagoutte

Theses

The relative merits of eight different coal fly ashes for use in the stabilization/Solidification of a waste containing both heavy metals and pentachlorophenol were investigated. Also studied, was the possible use of either untreated or treated (with hexade-cyl ammonium bromide) clay to enhance the stabilization of the organic. The sample composition was : 62% foundry baghouse dust (or 60% if 2% clay as added to the sample), 4.5% cement, 14% coal fly ash, 19.5% water. Pentachlorophenol was chosen as represen¬tative of the organic contamination. All tests were performed after curing the samples at 22°C, 98% Rh for 28 days. The …

Benzo(A)Pyrene Ingested From Composite Meals : Analysis And Method Development Related To Total Human Exposure, Che-Han Hsu

Theses

Polycyclic aromatic hydrocarbons including benzo[a]pyrene (BaP) have been known for many years to be environmental carcinogen. Moreover, B(a)P has often been used as an indi¬cator for the carcinogenic potency of environmental matter. One of its exposure pathways, ingestion, may possibly be more important than other routes, conventionally studied such as inhalation. The purposes of this thesis are 1) to analyze the B(a)P concentrations in weekly composite and some daily meals obtained in the Total Human Exposure to Environmental Substances (THEES) study, 2) to develop techniques which can measure the levels of B(a)P in foods accurately and effici¬ently, 3) to compare …

Degradation Of Refractory Organic Pollutants In Tar, Water And Soil Matrices By Ozone Or Hydrogen Peroxide With Ultraviolet Light, Liang-Jiun Uang

Theses

The objective of this research is to develop a method to degrade refractory Tar materials, higher molecular weight 3-5 ring Poly Aromatic Hydrocarbons (PAH's) or degrading these highly refractory PAH structures so that they are amenable to further treatment by biological or chemical methods. The process utilized to achieve this is to treat contaminated soils or tar materials with hydrogen peroxide or ozone plus ultraviolet light. Analysis of 27 specific PAH's was done by gas chromatograph (Flame Ionization Detection) for the reactants and products. The contaminated soil showed significantly lower levels of these PAH's after treatment.

Quantitative Determination Of Formaldehyde In Ambient Air, Wen-Shao Chou

Theses

Formaldehyde has been shown in the laboratory to play a critical role in the chemistry of polluted air. The method which we discuss in this paper was evaluated under practical field conditions in the Northern New Jersey Staten Island Urban Air Toxics Project. Formaldehyde in ambient air is concentrated and derived by passing a known quantity of air through a silica column impregnated with 2,4-dinitrophenylhydrazine (DNPH). The silica is eluted with acetonitrile and the concentration of formaldehyde is determined by High Performance Liquid Chromatograph (HPLC) with UV detection. A description of procedural details for coating silica cartridges with 2,4-DNPH acidified …

Microbial Competition In The Biodegradation Of Phenol, Mary Ellen Frank

Theses

Three phenol degraders were isolated from the mixed liquor of the Livingston, NJ municipal treatment plant. Shaker flask experiments using one of the degraders (a Pseudomonas sp.) resulted in the determination of its kinetic rate constants. The second phenol degrader (a Xanthamonas) lost its phenol degrading ability while being stored, and its kinetic rate constants could not be determined. The third phenol degrader (a Pseudomonas cepacia) formed flocs which interfered with the spectrophotometric determination of biomass and therefore its kinetic rate constants also could not be determined.

Mixed culture experiments were carried out using a the Pseudomonas sp. and a …