Pharmacology, Toxicology and Environmental Health Commons^™

Valorisation Of The Cider And Brewing Industry By-Products As Nutraceutical Ingredients, Sofia Reis

Doctoral

By-products from the cider and brewing industries, including apple pomace (AP) and brewer’s spent grain (BSG) respectively, constitute major environmental problems due to the large quantities produced every year. They are sources of valuable compounds such as protein, fibre, essential fatty acids, phenolic compounds and minerals, some of them with antioxidant and prebiotic properties. Their high nutritional value leads to their potential use as human food products and several applications have been considered recently. The aims of this work include i) the nutritional and compositional characterisation of AP, BSG and final extruded and baked prototypes containing these by-products and ii) …

Characterizing A Novel Monoclonal Ampa Receptor 1/2/3 Antibody In The Hippocampus And Prefrontal Cortex Of Rat, Monkey, And Human, Sebastian Aguiar

Pitzer Senior Theses

The excitatory, ionotropic glutamatergic AMPA receptor is the most common membrane-bound receptor in the central nervous system. AMPARs and the NMDA receptors are central to synaptic plasticity, memory, and mechanisms of neurodegeneration. The AMPAR is an obligate heterotetramer, composed of subunits GluA1-4. Subunit permutation determines ion conductance, trafficking and other functional characteristics. Few available antibodies are subunit-specific, disabling researchers from accurately visualizing differential AMPAR subunit distribution in the nervous system. This study sought to visualize a novel monoclonal GluA1/2/3 antibody with functional avidity for three of four receptor subunits and to characterize the ultrastructural localization of these receptors using confocal …

Multi-Component Microparticulate/Nanoparticulate Dry Powder Inhalation Aerosols For Targeted Pulmonary Delivery, Xiaojian Li

Theses and Dissertations--Pharmacy

The aim of the work was to design, manufacture, and characterize targeted multi-component dry powder aerosols of (non-destructive) mucolytic agent (mannitol), antimicrobial drug (tobramycin or azithromycin), and lung surfactant mimic phospholipids (DPPC:DPPG=4:1 in molar ratio). The targeted dry powder for inhalation formulation for deep lung delivery with a built-in rationale of specifically interfering several disease factors of chronic infection diseases in deep lungs such as cystic fibrosis, pneumonia, chronic bronchitis, and etc. The dry powder aerosols consisting of selected chemical agents in one single formulation was generated by using spray drying from organic solution.

The physicochemical properties of multi-component dry …

Mechanisms Of Cyclooxygenase-2-Dependent Human Aortic Smooth Muscle Cell Phenotypic Modulation, Oreoluwa O. Adedoyin

Theses and Dissertations--Pharmacy

Abdominal aortic aneurysm (AAA) is a disease of the aorta characterized by pathological remodeling and progressive weakening of the vessel resulting in the increased risk of rupture and sudden death. In a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, progression of AAAs is associated with reduced differentiation of smooth muscle cells (SMCs) at the site of lesion development. In the mouse model, the effectiveness of cyclooxygenase-2 (COX-2) inhibition for attenuating AAA progression is associated with maintenance of a differentiated SMC phenotype. However, the safety of COX-2 inhibitors is currently in question due to the increased …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Β-Lactam Estrogen Receptor Antagonists And A Dual-Targeting Estrogen Receptor/Tubulin Ligand, Niamh O'Boyle, Jade K. Pollock, Miriam Carr, Andrew Js Knox, Seema M. Nathwani, Shu Wang, Laura Caboni, Daniela M. Zisterer, Mary Meegan

Articles

Twelve novel β-lactams were synthesised and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC₅₀ values: 40 and 8 nM respectively) and ERβ (IC₅₀ values: 19 and 15 nM). β-Lactam 26 was the most potent in antiproliferative assays using MCF-7 breast cancer cells, and further biochemical analysis showed that it caused accumulation of cells in G₂/M phase (mitotic blockade) and depolymerisation of tubulin in MCF-7 cells. Compound 26 also induced apoptosis and downregulation …

Integrating Phage Therapy Into Western Medicine, Jacob B. Jaminet

Undergraduate Research Posters

The World Health Organization has described the rise of antibiotic use as a “global heath security emergency” (who.int). With the growing concern about antibiotic resistant bacteria, there has been an increased interest in bacteriophages. Bacteriophages are high-specific viruses that only infect bacteria. The use of bacteriophages medicinally to treat bacteria is called phage therapy. Research in phage therapy gained momentum until the introduction of antibiotics. While the USA and other Western countries accepted antibiotics, the Soviet Union and their satellite nations still continued to research phages. Since the funding for research was supplied by the Soviet military, the results of …

Comparison Of Eight Published Models For Estimating Vancomycin Clearance From Creatinine Clearance In Thai Adult Patients, Aim-On Pradoo, Thitima Wattanavijitkul, Darunee Chotiprasitsakul, Duangchit Panomvana

The Thai Journal of Pharmaceutical Sciences

This prospective study was performed to determine the best published model for estimating vancomycin clearance from creatinine clearance (CLcr) in Thai adult patients with CLcr greater than or equal to 30 ml/min. Data from 36 adult patients, who were giv...

Molecular Mechanisms Of Chemotherapeutic Resistance In Lung Cancer, Piyaparisorn Wongvaranon, Varisa Pongrakhananon, Pithi Chanvorachote

The Thai Journal of Pharmaceutical Sciences

Lung cancer mortality is mainly due to the high rate of chemotherapeutic resistance frequently found in lung cancer patients. In order to develop the novel strategies for effective treatment, the molecular basis regarding adaptive machineries of lung can...

Understanding The Medication Experiences Of Thai Patients Attending A Medication Therapy Management Clinic, Phantipa Sakthong, Win Winit-Watjana, Rungpetch Sakulbumrungsil

The Thai Journal of Pharmaceutical Sciences

The study aimed to explore Thai patients' medication experiences in five domains, i.e., attitudes, understanding, expectations and wants, concerns, and convenience of medicine use. This cross-sectional descriptive study was carried out using a qualitativ...

Identification And Antimicrobial Activity Of Streptomyces Strains From Thai Mangrove Sediment, Wongsakorn Phongsopitanun, Khanit Suwanborirux, Somboon Tanasupawat

The Thai Journal of Pharmaceutical Sciences

Two actinomycete strains, D2-1 and D2-2, were isolated from mangrove sediment sample collected from Samut Song Kram province, Thailand. On the screening of antimicrobial activity, the crude extracts of fermentation broth of both strains exhibited activit...

Gigantol-Induced Apoptosis In Lung Cancer Cell Through Mitochondrial-Dependent Pathway, Sopanya Charoenrungruang, Pithi Chanvorachote, Boonchoo Sritularak, Varisa Pongrakhananon

The Thai Journal of Pharmaceutical Sciences

Lung cancer is identified as a major cause of cancer-related death. Death in this cancer associates with the acquisition of apoptosis avoidance mechanism. Apoptosis, a programmed cell death mechanism, plays an important role on normal cell development an...

Balancing Accountability For Adverse Drug Reactions Under American Product Liability Law: Lessons For Thailand?, Sakda Thanitcul, Matthew Lim Braslow

The Thai Journal of Pharmaceutical Sciences

Drugs that are powerful enough to cure disease are powerful enough to do potential harm. This common saying among physicians is the central point of this paper. When harm to a patient does occur, the sense of society requires that where and when appropri...

Effects Of Nanosilver And Silver Nitrate Exposure On Fathead Minnows (Pimephales Promelas) And Zebrafish (Danio Rerio), Adam D. Hawkins

Electronic Theses and Dissertations

Silver nanoparticles (AgNPs) due to their unique antimicrobial properties are among the most widely utilized nanoparticle. Because of the nature of the products that utilize AgNPs, environmental release of AgNPs is inevitable. At greatest risk is the aquatic ecosystem due to known toxicity of the Ag + ion to aquatic organisms. Our goal was to use two fish models, fathead minnows (Pimephales promelas; FHMs) and zebrafish ( Danio rerio; ZFs), to study the effects of AgNPs on gill histopathology, Na+/K+-ATPase immunoreactivity, mucus production, bioaccumulation, particle uptake characterization, gill gene expression, and lethality in varying water parameters in comparison to the …

Impact Of Zinc Oxide Nanoparticles On Green Pea Plant & Seed Quality And Effects On Physiological Traits Of Green Peas, Corn, And Zucchini By Silver Nanoparticles, Arnab Mukherjee

Open Access Theses & Dissertations

The production and use of numerous engineered nanomaterials (ENMs) have increased exponentially over the past decade. Nanoparticles (NPs), ENMs possessing diameter between 1-100 nm, (NPs), are widely used in many applications. Worldwide consumption of NPs has increased their possible release into the environment. This, in turn, has elevated the extent of the potential impacts of NP exposure to living and non-living organisms. This is why the assessment of the impact of NPs on different environmental components, especially on plants, the producer in the food web, has become a very important aspect of nano-ecotoxicology. However, studies focusing on phytotoxicity and effects …

The Role Of Surface Chemistry In The Toxicity Of Manufactured Cerium Dioxide Nanomaterials To Caenorhabditis Elegans, Emily Kay Oostveen

Theses and Dissertations--Plant and Soil Sciences

Manufactured CeO₂ nanomaterials (CeO₂-MNMs) are used for a wide variety of applications including diesel fuel additives and chemical/mechanical planarization media. To test the effects of CeO₂-MNM surface coating charge on to model organism Caenorhabditis elegans, we synthesized 4 nm CeO₂ with cationic (DEAE-), anionic (CM-), and neutral (DEX) coatings. In L3 nematodes exposed for 24 hours, DEAE-CeO₂ induced lethality at lower concentrations than CM- or DEX-CeO₂. Feeding slightly decreased CeO₂ toxicity, regardless of coating. In L2 nematodes exposed for 48 hours with feeding, DEAE-CeO₂ caused lethality at the …

The Efficacy Of Prostaglandin Synthase Inhibition On Attenuating Pressure Overload Induced Cardiac Remodeling, Krishna T. Nagalla

Electronic Theses and Dissertations

Chronic hypertension has long been known to cause left ventricular remodeling. Although previous studies pointed towards inflammation as the pathological driver of cardiac remodeling, the exact mechanistic pathway associated with pressure overload-induced cardiac remodeling remains to be elucidated. In order to address this issue, we designed this study to determine pathways associated with pressure overload induced cardiac remodeling and identify therapeutic targets to attenuate this maladaptive cardiac remodeling. Rats with surgically constricted abdominal aorta were used as an animal model for pressure overload and associated Left ventricular (LV) structure and functional changes were measured by pressure-volume admittance catheterization. Human cardiac …

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

Wayne State University Dissertations

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

Bystander Effects Due To Neutrons, And Low-Dose Hyper-Radiosensitivity To Gamma Rays In Human Cells Using Cytogenetics, Isheeta Seth

Wayne State University Dissertations

Chapter 2:

Micronuclei have been used extensively in studies as an easily-evaluated indicator of DNA damage but little is known about their association with other types of damage such as nucleoplasmic bridges and nuclear buds. Radiation-induced clastogenic events were evaluated via the cytokinesis-block micronucleus assay in two normal human lymphoblastoid cell lines exposed to neutrons or gamma radiation. Micronuclei, nucleoplasmic bridges and nuclear buds were enumerated by recording the coincident presence of these endpoints within individual cells, and the associations among these three endpoints were evaluated for all treatment conditions. The common odds ratios for micronuclei and nucleoplasmic bridges were …

Adenosine A2b Receptor Effects On Post-Mi Remodeling And Cardiac Fibroblast Function, Enbo Zhan

Wayne State University Dissertations

Adenosine A_2B receptor (A_2BR) appear to contribute to chronic inflammation. This receptor is highly expressed in macrophages and cardiac fibroblasts, cells which play key roles in inflammation and healing following myocardial infarction (MI). A_2BR have been shown to induce collagen production and promote organ fibrosis, although the reports of A_2BR role on MI are limited and conflicting. The results of cardiac fibroblast (CF) studies however suggest that non-selective A_2BR stimulation inhibits collagen expression. The hypothesis of the present study was that deletion of A_2BR reduces adverse remodeling in post-MI, …

Dj-1 And Atp13a2: Two Proteins Involved In Parkinson’S Disease, Josephat M Asiago

Open Access Dissertations

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 0.3% of the total U.S. population, and its prevalence increases with age. Two neuropathological hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta, a region in the midbrain involved in initiating and sustaining movement, and the presence of cytosolic inclusions called Lewy bodies (LBs) in various brain regions. LBs are enriched with fibrillar forms of the presynaptic protein &agr;-synuclein (aSyn). Two autosomal recessive genes implicated in familial PD are PARK9, encoding the P-type ATPase ATP13A2, a lysosomal ATPase; and …

Characterization Of Small Conductance Calcium-Activated Potassium Channels In A Human Lens Epithelium Cell Line (B3), Wedad Ali Saqar

Browse all Theses and Dissertations

Small conductance calcium-activated potassium (SK) channels belong to the family of K+ channels. They play a significant role in cell volume regulation and in lens homeostasis, and thus are associated with cataract formation. This study was designed to demonstrate the presence of the four different isoforms of SK channels (SK1, SK2, SK3, and SK4) in human lens epithelial (HLE)-B3 cell line using Western blot (WB), immunofluorescence (IF), and reverse transcriptase coupled to the polymerase chain reaction (RT-PCR). Cataract formation involves SK-mediated K+ loss and gain of Na+ ions by lens cells. Further, it has been shown in previous studies that …

Inactivation Of At1a Receptors Attenuate Lactate Accumulation And Improve Cardiac Performance And Acid-Base Homeostasis During Endurance Exercise, Ahmad Mohammed Alhajoj

Browse all Theses and Dissertations

Angiotensin Type 1 (AT1) receptors are involved in cardiovascular pathology. Losartan, the AT1 receptor blocker, in combination with exercise has been shown to be effective in improving cardiac performance. The goal of the study was to investigate the role of AT1a receptors on cardiac function, and exercise tolerance in response to aerobic exercise using AT1a receptor knockout (AT1aKO) mice. An exercise wheel system was used for the exercise paradigm. Male (C57BL/6) wild type (WT) and AT1aKO mice were randomly assigned to four groups: WT control (n=6), WT exercise (WTEX, n=8), AT1a KO (KO) control (n=5), and AT1a KO exercise (KOEX, …

Early Increase Of Cd11c In Human Monocyte-Derived Dendritic Cells In The Presence Of A/California/07/2009 (H1n1pdm), Amber M. Braddock

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Influenza A continues to cause significant morbidity and mortality. Vaccine production time, viral antigenic variability and low vaccine efficacy contribute to the annual pandemics and seasonal epidemics. A better understanding of human immune responses to influenza A could result in more effective vaccines. Dendritic cells (DCs) play an important role in the initiation of immune responses. Populations of B lymphocytes secrete protective antibodies but the role of different populations of B cells in the protective response is unknown. In this thesis we developed assays to determine subclasses of influenza specific antibodies. Mononuclear cells were assessed using flow cytometry to identify …

The Modulatory Role Of Circulating Microvesicles In Endothelial Progenitor Cell Function Is Altered In T2dm, Hala Mustafa Ammar

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Circulating microvesicles (cMVs) are the extracellular MVs released from the cells in the blood and on the vascular wall. Our previous study demonstrates that cMVs of diabetic mouse are detrimental to endothelial progenitor cells (EPCs), which are known to be very important for maintaining normal endothelial function and structure. In this study, we compared the levels of circulating EPCs and EPC-derived MVs (EPC-MVs) in diabetic and healthy subjects. Also, the migration ability, apoptosis rate and reactive oxygen species (ROS) production of EPCs cultured from diabetic and healthy subjects were determined. More importantly, we evaluated whether cMVs from healthy subjects (ch-MVs) …

Expression, Characterization, Cloning And Functional Impact Of Slc12a5 In The Endocrine Pancreas, Shams Kursan

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The Slc12a5 gene encodes the neuron-specific electroneutral K+Cl- cotransporter-2 (KCC2), a constitutively active Cl- extruder. In mature neurons, KCC2 functionally predominates over other members of the Slc12a family, particularly the Na+K+2Cl- cotransporter-1 (NKCC1), a ubiquitous Cl- loader. Therefore, KCC2 keeps and maintains the intracellular chloride concentration ([Cl-]i) below values predicted by thermodynamic equilibrium and in doing so, KCC2 plays a key role in neuron physiology: it makes possible the inhibitory action of neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine. Neurons and insulin-secreting pancreatic ß-cells share many genes and functions. Indeed, neuron-specific genes have been also found in ß-cells whereas …

Effect Of The Broad-Spectrum Caspase Inhibitor Q-Vd-Oph On Neurodegeneration And Neuroinflammation Of Sarin Exposed Mice, Ekta J. Shah

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Organophosphates (OP) cause CNS hyperstimulation resulting in seizures, convulsions and brain damage. Sarin is a toxic nerve agent used in Syria, the Gulf War and in terrorist attacks in Japan. Exposure to sarin is associated with presence of dead neurons, activation of astrocytes, microglia and neuroinflammation. Since, cell death and neuroinflammation are found in sarin exposed animals, we evaluated the efficacy of Q-VD-OPh, a broad spectrum caspase inhibitor that prevents cell death and has anti-inflammatory properties. Currently, treatment for sarin exposures is effective only if administered within 30-40 minutes of exposure. In this study, adult female C57BL/6 mice were subjected …

Increased Urinary Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Type 2 Diabetic Patients, Sridevi Gutta

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Chronic Kidney Disease (CKD) has reached epidemic proportions affecting more than 20 million adults in the US. CKD is routinely diagnosed and defined as reduced glomerular filtration rate (GFR), increased urinary albumin creatinine ratio (UACR) or both. Diabetes, hypertension and obesity share a major part in causing CKD. Angiotensin (1-7) (Ang (1-7)) is a vasodilator that plays an important renoprotective role in the renin angiotensin system, counteracting the vasoconstrictor and proliferative effects of Ang II. ACE2 and NEP which form Ang (1-7) by degrading Ang II and Ang I, respectively. A Disintegrin and Metalloproteinase (ADAM) 17, which is responsible for …

Effect Of Nonthermal Plasma On Quality Of Fresh Produce, Nrusimhanath Misra

Doctoral

No abstract provided.