Pharmacology, Toxicology and Environmental Health Commons^™

Numerically Modelling Time And Dose Dependent Cytotoxicity, Hugh Byrne, Marcus A. Maher

Articles

Dose-response curves are fundamental tools of in vitro toxicology, extensively employed in toxicant or drug screening. They are expressed by a variety of end-points and assays, measured at different time-points in a choice of cell-lines, but are typically quantified only using the mean concentration for 50% response (e.g. drug efficacy or pathway inhibition) as an indicator of overall effect. However, the response is the result of a complex and dynamic cascade of events which occur between the initial exposure and the measured end-point, and the characteristic rates of the contributing stages govern the dose response and ultimately the measured characteristic …

The Analgesic-Like Properties Of Alcohol In Animal Models Of Chronic Pain, Bradley Neddenriep

Theses and Dissertations

Chronic pain and excessive alcohol consumption are individually problems in our society today. Alcohol Use Disorder (AUD) affects 15.1 million adult Americans each year. Chronic pain affects over 100 million people annually in the United States. However, there is growing evidence suggesting that these two conditions can often be interrelated with chronic pain increasing consumption of alcohol, and excessive alcohol consumption increasing pain that leaves a feedback cycle trapping millions of patients in an ever worsening spiral. Large population-based studies show an association between pain and alcohol abuse, suggesting a link between increased alcohol use and reduced pain. While rodent …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra

Theses and Dissertations

Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT_2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT_2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT_2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT_2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in …

An Investigation On The Role Of Β-Arrestin 2, Protein Kinase C And Sex On The Mechanism Of Morphine Tolerance In The Mouse Ileum, Karan Hitesh Muchhala

Theses and Dissertations

Opioids such as morphine are frequently used in the clinic to treat pain. However, the perennial bane of chronic opioid use is the rapid development of tolerance to the analgesic effects but delayed development of tolerance to the respiratory depressant and constipating effects. As constipation is one of the most common opioid-related adverse effects in humans, it is important to delineate mechanisms that drive opioid tolerance in the ileum and lack of it in the colon. The overarching goal of this thesis was to investigate mechanisms of morphine tolerance in the ileum by comparing the mechanism of morphine tolerance in …

Electrochemical Detection Of Fentanyl Using Screen-Printed Carbon Electrodes With Confirmatory Analysis Of Fentanyl And Its Analogs In Oral Fluid Using Liquid Chromatography-Tandem Mass Spectrometry, Colby E. Ott

Graduate Theses, Dissertations, and Problem Reports (ETD)

Utilizing screen-printed carbon electrodes (SPCEs), a fast, simple, and sensitive approach toward the detection, identification, and quasi-quantitation of fentanyl was achieved both in an electrochemical cell and as a drop on the electrode surface. Electro-oxidation of fentanyl at the electrode was demonstrated using adsorptive stripping square-wave voltammetry between -0.5 V and +1.6 V with 100 mM Tris-HCl buffer at pH 8.5 as supporting electrolyte. Parameter optimization was conducted during method development to include supporting electrolyte and pH, electrochemical technique, pre-treatment and equilibration time, and various surface modifications. The simplest method utilizing an unmodified SPCE was determined to be appropriate for …

Investigating The Antiviral Effects Of Vig-3 From Rainbow Trout, Shanee Herrington-Krause

Theses and Dissertations (Comprehensive)

Rainbow trout is the most farmed fish in Ontario, and thus is economically important to the province. Despite this, there is a lack of understanding regarding fish innate immunity, specifically with regards to interferon-stimulated genes (ISGs) and their antiviral effector functions. ISGs are the workhorses of the innate antiviral response, operating together to limit each step of virus replication. The Viral Hemorrhagic Septicemia Virus (VHSV) induced gene (Vig)-3 is a newly identified ISG within many fish species and is homologous to ISG-15 in mammals. It is a small ubiquitin-like protein inducible by type I interferon (IFN-I), and is suggested to …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Negative Effects Of Common Herbicides On Non-Target Invertebrates, Debbi Albanese

College of Graduate Studies: Theses & Dissertations

Three herbicide formulations, Roundup® Ready to Use Weed and Grass Killer, Bayer Advanced Southern Weed Killer for Lawns and Pure 20% Vinegar Solution were directly applied to eggs of four species of butterflies, Danaus plexippus, Papilio cresphontes, Papilio polyxenes and Papilio troilus. Roundup and Bayer Advanced containing 2,4-D, mecoprop-p and dicamba significantly reduced hatch success in all four species. Lethal and sublethal effects of these herbicides on the earthworm, Eisenia andrei, was also examined. Direct contact by E. andrei with a heavy dose of the herbicides applied to tops of soil 24 hours prior was lethal to earthworms. …

Synthesis Of N-Heterocyclic Molecules And Their Applicability Towards Ion Sensing: Polymeric Chemosensors, Aikohi M. Ugboya

College of Graduate Studies: Theses & Dissertations

Critical to biological and environmental processes are anions because often times their relative concentration in our body can be an indicator of one’s well-being. Therefore, highly sensitive and cost-efficient methods for ions recognition is necessary for human health. In recent times, polymeric chemosensors have become a vital tool for sensing ions because of its higher sensitivity and good mechanical properties compared to their monomeric counterparts. These sensors are designed to produce a measurable response in the presence of a targeted ion such as an electrochemical or optical signal. The unique structure and the photophysical properties of the 1,2,3-triazole core coupled …

An Audience With Pharmaceutical Regulators, Academia And Industry 2019: The Role Of Quality Risk Management (Qrm) And Knowledge Management (Km) In Medicinal Product Realisation For Patients In The 21st. Century, Anne Greene (Editor), Kevin O'Donnell (Editor), Anne Murphy (Editor), Elaine Harris (Editor)

Books

A monograph based on a seminar organised by the School of Chemistry & Pharmaceutical Science, Technological University Dublin, with the Health Products Regulatory Authority, and with Regulatory Science Ireland, 4th. April, 2019.

Raman Spectroscopic Analysis Of Saliva For The Diagnosis Of Oral Cancer: A Systematic Review, Genecy Calado, Isha Behl, Amuthachelvi Daniel, Hugh Byrne, Fiona Lyng

Articles

Abstract Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, and new protocols for routine and early detection are required. Raman spectroscopy is an optical based method that can provide sensitive and non-invasive real time detailed information on the biochemical content of a sample like saliva, through the unique vibrations of its constituent molecules and this is sensitive to changes associated with disease. A comprehensive systematic review of the available scientific literature related to Raman spectroscopy of human saliva for diagnosis of OSCC was performed. The 785 nm laser line was most applied wavelength along with …

Principal Components Analysis Of Raman Spectral Data For Screening Of Hepatitis C Infection, A. Dita, H. Nawaz, T. Mahmood, M. Tahir, N. Rashid, Muhammad Mudassar, A.A.H. Alsaadi, Hugh Byrne

Articles

In the current study, Raman spectroscopy is employed for the identification of the biochemical changes taking place during the development of Hepatitis C. The Raman spectral data acquired from the human blood plasma samples of infected and healthy individuals is analysed by Principal Components Analysis and the Raman spectral markers of the Hepatitis C Virus (HCV) infection are identified. Spectral changes include those associated with nucleic acidsat720 cm−1, 1077 cm−1 1678 (CO stretching mode of dGTP of RNA), 1778 cm−1 (RNA), with proteins at 1641 cm−1(amide-I), 1721 cm−1(CC stretching of proteins) and lipids at 1738 cm−1(CO of ester group in …

A Review Of Human Factors And Food Safety In Ireland, Ciara Walsh, Maria Chiara Leva

Articles

Increased product shelf-life and globalisation have led to longer and vastly more complicated food chains; potentially presenting greater opportunity for contamination and microbial growth to occur. Modern food safety management systems risk assess hazards (based on current scientific data) and strive to control these, often extensive and convoluted, food production/supply chains through appropriate good hygiene practices (GHP) and HACCP. Contamination of food as a result of human error can undermine even the most carefully prepared and executed HACCP system – culminating in foodborne infection, outbreaks, reputable damage, and erosion of consumer trust. This paper provides a review on the effect …

Dentistry: Are Stem Cells The Future?, Tova Zemel

The Science Journal of the Lander College of Arts and Sciences

Stem cell research is currently advancing in every area of medicine. New information about regenerating stem cells is being uncovered on a daily basis. An area of stem cells that has not been focused on until recently is the use of dental stem cells. The objective of this paper is to elucidate the most current research about dental stem cells. Much of what is discussed in this paper has not been implemented yet, and is still in clinical trials. Dental stem cells are important because they could be an alternative way of treating caries, performing root canals, and other traumas …

Capsacin And Analgesia, Mimi Kornwasser

The Science Journal of the Lander College of Arts and Sciences

Capsaicin is the active compound responsible for the pungency of hot chilli. Research has discovered its ability to desensitize peripheral nociceptive fibers which is useful in treating chronic pain disorders, specifically neuropathic pain syndromes. Capsaicin treatment comes in a variety of mediums including patches and creams and has been clinically proven to bring relief to patients with disorders such as post herpetic neuralgia, chronic regional pain syndrome and HIV related neuralgia. Exciting new forms of treatment are also in development and promise breakthroughs in the near future in this relatively young field of capsaicin-based analgesia.

The Effects Of Rf-Emf On The Child Brain, Aaron Skaist

The Science Journal of the Lander College of Arts and Sciences

It has long been debated whether or not cell phones have a deleterious effect on the brain. Recent studies indicate that the electro-magnetic field emitted by cell phones called RF-EMF is linked to cancer. Guidelines created to limit the exposure have not been changed since 1981 and do not consider children. The mechanism thought to cause cancer is reactive oxygen species (ROS), which cause the creation of micronuclei. RF-EMF poses a greater threat to children than adults. This is due to the major anatomical differences between the head of a child and an adult. The skull of a child is …

Car T-Cell Therapy For Acute Lymphoblastic Leukemia, Esther Langner

The Science Journal of the Lander College of Arts and Sciences

Despite all the available therapies, Acute Lymphoblastic Leukemia (ALL) remains extremely difficult to eradicate. Current available therapies, which include chemotherapy, radiation, and stem cell transplants, tend to be more successful in treating children than adults. While adults are more likely than children to relapse after treatment, the most common cause of treatment failure in children is also relapse. Improved outcomes for all ALL patients may depend upon new immunotherapies, specifically CAR T-cell therapy. CAR T-cell therapy extracts a patient’s own T-cells and modifies them with a CD19 antigen. This modification allows the new T-cells to recognize and kill cancer cells …

Full Issue: Volume 12, Number 2

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Triggers Of Spermatogenesis, Moses Bibi

The Science Journal of the Lander College of Arts and Sciences

Of the 7% of men affected with infertility, about 54% suffer from pre-testicular and/or testicular factor induced azoospermia/ oligospermia. This agenesis of spermatozoa has been the subject of much andrology research over the past 50 years, with a particular focus in the triggers of spermatogenesis. While much of their work is limited to murine populations, researchers have put a lot of emphasis on the spermatogonial stem cell (SSC) niche as the source of the trigger(s). By following physiological patterns exhibited in the seminiferous epithelium, researchers have been able to detect distinct morphological stages that correlate with spermatogonial germ-line action. Different …

The Effects Of Aging On Skeletal Muscle Atp Production, Chaya Abboudi

The Science Journal of the Lander College of Arts and Sciences

The study of the aging process and its prevention is an incredibly popular field; the natural course of the human body is to age and theories abound on how to avoid it. Age affects every system and pathway of the body and alters many of the bodily functions. This paper, using articles from Touro’s library database examines the different areas in which aging negatively affects ATP production. The multifaceted process associated with the production of ATP in the human body was analyzed. Several features such as the mitochondria, physical activity, and hormones are linked to ATP production and the relationship …

Should Subclinical Hypothyroidism Be Treated?, Rachel Kaufman

The Science Journal of the Lander College of Arts and Sciences

Subclinical Hypothyroidism, SCH, has been detected with increasing frequency in recent years and has brought about major controversies regarding management and treatment [Meier et al., 2001]. The condition is characterized as having a high concentration of thyroid stimulating hormone, yet normal thyroid hormone levels and is often asymptomatic. Scientific articles retrieved from various databases helped determine some of the long term risk factors associated with SCH, including progression to overt hypothyroidism, fatty liver disease, cardiovascular disease, neuropsychiatric complications and reproductive malfunctions. Studies determining the clinical and metabolic effects of L-thyroxine hormone replacement therapy on symptoms and potential risks of SCH …

Are There Any Viable Treatments For Age Related Macular Degeneration?, Michael Radparvar

The Science Journal of the Lander College of Arts and Sciences

Stem cells seem to offer an alternative venue for treating many cell related diseases, such as age-related macular degeneration (ARMD). ARMD is a progressive neurodegenerative medical condition, which primarily affects the retinal pigmented epithelium (RPE), resulting in degeneration of photoreceptors. Scientists have been successful in implanting stem cells into the eyes of rats. These injected cells sustained visual function and photoreceptor integrity without any cancerous cell formation. There are numerous treatments available to slow down the progression of ARMD. Depending on the type of ARMD, doctors may either recommend leading a healthier lifestyle or that one should undergo surgery. Numerous …

The Role Of Diet In Inflammatory Bowel Diseases, Aviva Smilow

The Science Journal of the Lander College of Arts and Sciences

Inflammatory Bowel Disease encompasses two diseases, Crohn’s Disease and Ulcerative Colitis. During the last 70 years the evolving of diet in the industrialized countries has led to the utilization of foods that have been processed rather than those in their more natural original state. This increase in the processing of foods has been correlated with the more recent occurrence of metabolic diseases such as Inflammatory Bowel Disease. Patients suffering from this problem exhibit lesser amounts of anti-inflammatory bacteria such as Roseburia and Faecalibacterium and increased amounts of pro-inflammatory bacteria Escheria and Fusobacterium. Since diet directly alters the composition of the …

Behavioral Impairment Following Gestational Exposure To Titanium Dioxide Nanomaterial Aerosols In Male And Female Rats, Matthew Leland Eckard

Graduate Theses, Dissertations, and Problem Reports (ETD)

Engineered nanomaterials (ENMs) are beginning to be recognized as hazardous to human and animal health. Titanium dioxide (TiO2) is primarily used as a whitening agent in paints, plastics, and sunscreens. While relatively inert in its bulk form, nano-TiO2 (diameter) can produce prolonged inflammation and oxidative stress in target tissue. Recently, the potential for nano-TiO2 to cause neuroinflammation and damage has heightened concerns about its continued use. One important concern is that nano-TiO2, and other metal oxide ENMs, may affect fetal neurodevelopment. Accordingly, it is imperative to screen ENMs, like TiO2, for possible neurotoxicity following developmental exposures. The current set of …

The Acute Effect Of Propanil On Reproductive Hormones, Ovarian Gene Expression And Splenic Cells In C57bl/6 Female Mice, Malia Danielle Berg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Earlier evidence indicates exposure to propanil, a post-emergent herbicide used on rice and wheat fields, increases the number of antibody-secreting cells (ASC) in the spleen of mice after immunization with heat-killed Streptococcus pneumoniae (HKSP, 2x10⁸ CFU). Interestingly, an intact hypothalamic-pituitary-gonadal (HPG) axis is required for this immune response assessed on day 7-10 after immunization in female mice. Hence, an overarching premise is that propanil arbitrates the connection between the reproductive and immune system by altering the concentration of hormones involved in the HPG axis, which may then affect the populations of splenic cells. Hypotheses were tested with C57Bl/6 female …

Ground Ingredients: Analysis Of Lead Exposure In The California Condor’S (Gymnogyps Californianus) Ground Foraging Habitat, Evan Michael Mcwreath

Graduate Theses, Dissertations, and Problem Reports (ETD)

The California Condor (Gymnogyps californianus) is a critically endangered species that reached its nadir in 1987 with a population of 27 birds in the wild. Intensive management efforts have been implemented to aid the condors’ recovery, however, anthropogenic factors, like use of lead ammunition, continue to cause fatalities in this vulnerable population. Lead toxicosis, which is responsible for approximately 40% of all condor deaths since 1992, is one of the most significant threats to condors. In birds lead poisoning leads to neurological dysfunction, reproductive impairment, immune suppression, gastrointestinal disturbance, anemia, and ultimately increased vulnerability to predation, starvation, and infection. For …

Acute And Repeated Effects Of Synthetic Cannabinoid Agonism And Cannabinoid Receptor 1 Positive Allosteric Modulation, Kristen R. Trexler

Graduate Theses, Dissertations, and Problem Reports (ETD)

Recent years have seen a rise in the diversity and use of synthetic cannabinoids. Currently, there is little known about the effects of specific synthetic cannabinoid compounds. As such, little research has been done evaluating the acute and chronic effects of synthetic cannabinoid administration or the development of tolerance and withdrawal. The present study aimed, in part, to evaluate the acute and repeated effect of a third-generation synthetic cannabinoid, AB-FUBINACA. Mice were treated with AB-FUBINACA (0.1-3 mg/kg, i.p.) or vehicle and were tested repeatedly in the tetrad battery of assays, which included tests of catalepsy, antinociception, hypothermia, and locomotor activity. …

Effects Of E-Cigarette Flavoring Chemicals On Human Macrophages And Bronchial Epithelial Cells, Anna Manzi Morris

Graduate Theses, Dissertations, and Problem Reports (ETD)

E-cigarettes and vapes are relatively new devices which are popular among young adults and teens. These devices vaporize an “e-liquid” for the user to inhale, which typically contains a mixture of propylene glycol (PG), vegetable glycerin (VG), varying concentrations of nicotine, and flavoring chemicals. Due to these flavoring chemicals being intended for ingestion as a food additive, their respiratory health effects are not well understood. Thousands of e-cigarette flavors are available on the market, many of which have the potential for toxicity. The majority of e-liquid flavoring chemicals (ELFCs) have not been tested for inhalation safety. In this study, we …

Metal Nanomaterials: Immune Effects And Implications Of Physicochemical Properties On Sensitization, Elicitation, And Augmentation Of Allergic Disease, Katherine Adair Roach

Graduate Theses, Dissertations, and Problem Reports (ETD)

Many allergenic metals are being manufactured in nanoparticulate forms. Although the decreased size profile of metal nanomaterials has been consistently associated with more pronounced lung toxicity compared to larger materials, it is unclear if metal-induced immunotoxic effects exhibit a similar size-dependency.

The central hypothesis of these studies was that metal nanoparticles cause more pronounced immunomodulatory effects on allergic processes than larger forms of respective metals. Moreover, it was anticipated that, similar to their inflammatory potential in airways, the magnitude of these responses would correlate best with the dose metric of surface area.

The first set of studies utilized fine and …