Pharmacology, Toxicology and Environmental Health Commons^™

Contractile Response Of Bovine Lateral Saphenous Vein To Ergotamine Tartrate Exposed To Different Concentrations Of Molecularly Imprinted Polymer, Manoj B. Kudupoje, James L. Klotz, Alexandros Yiannikouris, Karl A. Dawson, Kyle R. Mcleod, Eric S. Vanzant

Animal and Food Sciences Faculty Publications

Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response …

Selective Inhibition Of Ctcf Binding By Ias Directs Tet-Mediated Reprogramming Of 5-Hydroxymethylation Patterns In Ias-Transformed Cells, Matthew Rea, Tyler Gripshover, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Methylation at cytosine (5mC) is a fundamental epigenetic DNA modification recently associated with iAs-mediated carcinogenesis. In contrast, the role of 5-hydroxymethylcytosine (5hmC), the oxidation product of 5mC in iAs-mediated carcinogenesis is unknown. Here we assess the hydroxymethylome in iAs-transformed cells, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks. Moreover, this pathologic iAs-mediated carcinogenesis is characterized by a shift toward a higher hydroxymethylation pattern genome-wide. At specific promoters, hydroxymethylation correlated with increased gene expression. Furthermore, this increase in hydroxymethylation occurs concurrently with an upregulation of ten-eleven translocation (TET) enzymes that oxidize 5-methylcytosine (5mC) in DNA. To …

Study Of The Mechanism Of Action For Ru(Ii) Polypyridyl Complexes As Potential Anticancer Agents, Yang Sun

Theses and Dissertations--Chemistry

Application of chemotherapeutic agents in current cancer treatment has been limited by adverse effects as poor selectivity results in systemic toxicity; most chemotherapy approaches also experience inherited or acquired drug resistance which lead to reduced treatment outcome. Research efforts have focused on the discovery of novel chemotherapies that overcome the limitations mentioned above. Ru(II) polypyridyl complexes with anti-cancer properties have been extensively studied as traditional cytotoxic agents and photodynamic therapy agents due to their photophysical and photochemical characteristics.

Most research has focused on the design of Ru(II) polypyridyl complexes that have affinities to nucleic acids as inspired by the classic …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.

Effects Of Crude Oil On Tumor Suppressor P53 Polymorphisms In Laboratory-Exposed Atlantic Killifish, Fundulus Heteroclitus, Allison Margaret Nadler

Seton Hall University Dissertations and Theses (ETDs)

Polycyclic aromatic hydrocarbons (PAHs), constituents of crude oil, are implicated as a potent source of adverse toxicological effects on living organisms. To model the effects of PAHs in response to environmental oil spill disasters a species of killifish (Fundulus heteroclitus) was captured and exposed to crude oil in a laboratory-controlled setting. Over a period of 7 days, fish were dosed with crude oil by gavage, culled, and organs were harvested for analysis. Excitation-emission matrix spectroscopy (EEMS) of gall bladder tissue homogenates was used to verify exposure. Effects of PAHs on the p53 gene were evaluated as an indicator …

Investigating The Toxicity And Accumulation Of 2,4-Dichlorophenoxyacetic Acid (2,4-D) And Glyphosate In Eisenia Fetida, Caitlin Lazurick, Nicole Lidzbarski, Rachel Owings, Jeff Brotherton, Edna Steele

Journal of the South Carolina Academy of Science

Glyphosate, the main ingredient in Roundup^®, is the most widely used herbicide in the world. It is also used in combination with another effective herbicide, 2,4-D, in the formulation called Enlist Duo^®. The EPA approved the use of Enlist Duo^® on certain crops including those genetically modified to be resistant to both herbicides. The predicted significant increase in the use of these herbicides raised concerns from the general public because both compounds have been classified as possibly or probably carcinogenic. Since herbicides are applied directly to vegetation, the safety of organisms that come in contact …

Carbon Sequestration In The Cloud Forest: A Comparative Evaluation Of Aboveground Biomass Carbon Stock Potential In The Río Guajalito Reserve, Elli Mapstone

Independent Study Project (ISP) Collection

As carbon dioxide levels in the atmosphere continue to rise at a rapid rate, it is necessary to understand how forests can both contribute to CO₂ levels but also stop them from rising. Carbon sequestration levels in tropical montane cloud forests are a relatively understudied topic. Gathering carbon stock levels is the first step necessary to start a REDD+ project. Carbon stock levels can be studied on a global, regional or local level. This study used the University of Oxford/ Global Ecosystems Monitoring Network (GEM) methodology to examine carbon sequestration levels of aboveground biomass, specifically ground litter, large branches …

Effects Of Carboxylated Nanodiamonds On Macrophages During And After Differentiation, Maisoun E. Bani Hani

Biological Sciences Theses & Dissertations

Nanodiamonds (ND) are a carbon-based nanomaterial that are increasingly being proposed for developing novel imaging techniques, as carriers of biomolecules and therapeutic drugs, as coatings for implants, and for other biomedical applications. The exceptional chemical, mechanical, and optical properties of ND make this material suitable in a wide range of fields. The application of ND in the biomedical field is attractive but requires more in-depth investigation into the safety of ND and its interactions with different cells and systems. The effects of ND on the immune system are not fully understood or investigated and there are several controverting reports regarding …

Transient And Permanent Changes In Dna Methylation Patterns In Inorganic Arsenic-Mediated Epithelial-To-Mesenchymal Transition, Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Chronic low dose inorganic arsenic exposure causes cells to take on an epithelial-to-mesenchymal phenotype, which is a crucial process in carcinogenesis. Inorganic arsenic is not a mutagen and thus epigenetic alterations have been implicated in this process. Indeed, during the epithelial-to-mesenchymal transition, morphologic changes to cells correlate with changes in chromatin structure and gene expression, ultimately driving this process. However, studies on the effects of inorganic arsenic exposure/withdrawal on the epithelial-to-mesenchymal transition and the impact of epigenetic alterations in this process are limited. In this study we used high-resolution microarray analysis to measure the changes in DNA methylation in cells …

Enhanced Physical Endurance And Improved Memory Performance Following Taurine Administration In Rats, Irfan Sajid, Saara Muddasir, Shaista Emad, Zehra Batool, Saima Khaliq, Lubna Anis, Saiqa Tabassum, Syeda Madiha, Laraib Liaquat, Sadia Sadir, Tahira Perveen, Saida Haider

Department of Biological & Biomedical Sciences

Energy drinks enhance physical endurance and cognitive ability. The ingredients present in these drinks are considered as ergogenic and have memory boosting effects. In the present study effects of taurine administration for one week was monitored on physical exercise and memory performance in rats. Animals were divided into two groups namely control and test. Taurine was injected intraperitoneally to the test group at the dose of 100mg/kg. After one week of treatment rats were subjected to physical exercise and memory task. Results of this study revealed that rats injected with taurine for one week exhibited improved muscular strength as well …

Industrial Grade 2d Molybdenum Disulphide (Mos2): An In-Vitro Exploration Of The Impact On Cellular Uptake, Cytotoxicity, And Inflammation, Caroline Moore, Hugh Byrne, Jonathan N. Coleman, Yuri Volkov, Jennifer Mcintyre

Articles

The recent surge in graphene research, since its liquid phase monolayer isolation and characterization in 2004, has led to advancements which are accelerating the exploration of alternative 2D materials such as molybdenum disulphide (MoS2), whose unique physico-chemical properties can be exploited in applications ranging from cutting edge electronic devices to nanomedicine. However, to assess any potential impact on human health and the environment, the need to understand the bio-interaction of MoS2 at a cellular and sub-cellular level is critical. Notably, it is important to assess such potential impacts of materials which are produced by large scale production techniques, rather than …

Applied Drug Development And Combinatorial Strategies For Antimicrobial Treatment, Steven K. Lai Hing

Andrews Research Conference

Streptococcus mutans JH1140 is a strain of bacteria which produces a lantibiotic product, named mutacin 1140. Mutacin 1140 has been shown to be effective at inhibiting Gram-positive bacterial infections caused by Staphylococcus aureus and Streptococcus pneumoniae. Mutacin 1140 is a ribosomally synthesized peptide antibiotic that undergoes extensive posttranslational modifications (PTM). We have found that Mutacin 1140 and an aminoglycoside, Kanamycin, when combined together, act synergistically against Staphylococcus aureus. This was determined by performing serial kill curve dilution overlays on solid media, followed up with kill curve by microdilution plate, and most recently confirmed with kill curve CFU count plates …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Physiological Effects Of Five Different Marine Natural Organic Matters (Noms) And Three Different Metals (Cu, Pb, Zn) On Early Life Stages Of The Blue Mussel (Mytilus Galloprovincialis), Lygia Sega Nogueira, Adalto Bianchini, Scott Smith, Marianna Basso Jorge, Rachael L. Diamond, Chris M. Wood

Chemistry Faculty Publications

Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis—one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of …

Therapeutic Modulation Of Cancer Metabolism With Dichloroacetate And Metformin, Nathan Patrick Ward

USF Tampa Graduate Theses and Dissertations

The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin’s reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in the VM-M3 model of GBM. We demonstrated that metformin potentiated DCA-induced superoxide production and that this was required for enhanced cytotoxicity towards VM-M3 cells with the combination. Similarly, rotenone enhanced oxidative stress resultant …

Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs, Nathan Puckett

Masters Theses & Specialist Projects

Platinum complex drugs such as cisplatin have been used as highly successful chemotherapy drugs since the 1970s. We are interested in how the ligands attached to cisplatin analogs influences their reactivity with biologically relevant targets along with time and amount. For this study, reactions were conducted to determine the reactivity between different platinum compounds and the protein bovine serum albumin. Various platinum compounds with different ligands were reacted in varying amounts with albumin in ammonium acetate buffer for either 1 hour, 4 hours, or 24 hours. Each reaction was quenched after the designated reaction time by dialysis and the platinum …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Epigenomic Reprogramming In Inorganic Arsenic-Mediated Gene Expression Patterns During Carcinogenesis, Meredith Eckstein, Rebekah Eleazer, Matthew Rea, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Arsenic is a ubiquitous metalloid that is not mutagenic but is carcinogenic. The mechanism(s) by which arsenic causes cancer remain unknown. To date, several mechanisms have been proposed, including the arsenic-induced generation of reactive oxygen species (ROS). However, it is also becoming evident that inorganic arsenic (iAs) may exert its carcinogenic effects by changing the epigenome, and thereby modifying chromatin structure and dynamics. These epigenetic changes alter the accessibility of gene regulatory factors to DNA, resulting in specific changes in gene expression both at the levels of transcription initiation and gene splicing. In this review, we discuss recent literature reports …

Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …

Ck2—An Emerging Target For Neurological And Psychiatric Disorders, Julia Castello, Andre Ragnauth, Eitan Friedman, Heike Rebholz

Publications and Research

Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full …

Survival Model Of Intrahepatic Cholangiocarcinoma; Sex As A Biological Variable, Mary A. Phillippi, Justin L. Mott, Cody J. Wehrkamp, Ying Xie, David Oupicky, Ashley M. Mohr, Bailey A. Stringham

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho

Legacy Theses & Dissertations (2009 - 2024)

Expression of metabolic enzymes Cytochrome P450 (CYP) is highly affected by drugs, diseases, age and gender. The Intestinal microflora has been suggested to play a role in regulating CYP expression and antibiotic treatments would lead to changes in level and composition of microbiota in mouse gut. This study aims to analyze CYP expression changes in the liver and small intestine resulted from the reduction of intestinal microflora by antibiotics. Impacts on bile acid signaling were also analyzed for a better comprehension of the mechanisms involved in this modulation. Female C57BL/6J mice (9- to 13-week old) were treated with ampicillin (AMP) …

Biochemical, Structural, And Drug Design Studies Of Norovirus And Zika Virus Proteases, Ben Kuiper

Wayne State University Dissertations

Noroviruses, which are the leading cause of acute gastroenteritis, cause an estimated 677 million infections and 213,000 deaths each year worldwide. Noroviruses are classified into seven genogroups (GI-GVII); GI, GII, and GIV have been shown to be infectious in humans. However, GII noroviruses cause the majority of outbreaks (89%). No pharmacologic treatment or vaccine currently exists to treat or prevent norovirus infections.

Recently, the development of a norovirus replicon system, a murine model of norovirus infection, and the development of a biochemical protease assay have allowed for the design and development of norovirus inhibitors. However, the replicon and biochemical assay …

Patholigical And Prognostic Role Of Mdig In Pancreatic Cancer, Srinivas Ashok Kumar

Wayne State University Theses

Pancreatic cancer is a highly aggressive malignant disease having very limited therapeutic options that ultimately results in its poor prognosis. It is still elusive on the etiology and tumorigenic mechanisms of pancreatic cancer. In the present report, we provide evidence showing involvement of the mineral dust-induced gene (mdig) in the pathogenesis and prognosis of the pancreatic cancer. Using immunohistochemistry approach on human pancreatic cancer tissue microarray, we found differential expression of mdig in pancreatic adenocarcinoma and normal pancreas. Based on the staining intensities of mdig in these tissue samples, we found that 12% of the cancer tissues were strongly positive …

Sex Differences In The Subjective Effects Of Oral Δ9-Thc In Cannabis Users, Jessica S. Fogel, Thomas H. Kelly, Philip M. Westgate, Joshua A. Lile

Behavioral Science Faculty Publications

Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ⁹-tetrahydrocannabinol (Δ⁹-THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ⁹-THC and placebo and then received a range of Δ⁹-THC doses (0, 5, 15 and a “high” dose of …

Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted

Electronic Theses and Dissertations

Flavonoids are polyphenolic secondary metabolites found in plants that have bioactive properties including antiviral, antioxidant, and anticancer. Two isomeric flavone were extracted from Gnaphalium elegans and Achyrocline bogotensis, plants used by the people from the Andean region of South America as remedies for cancer. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5, 7–dihydroxy- 3, 6, 8 trimethoxy flavone/ flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3, 5–dihydroxy-6, 7, 8–trimethoxy flavone/ flavone B) have shown antineoplastic activity against colon cancer cell lines dependent upon their differentiation status. Pharmacokinetic studies reported herein were used to determine dosing for antitumor assays, as well as determine target tissue concentration. These included the …

In Vitro Monitoring Of Time And Dose Dependent Cytotoxicity Of Aminated Nanoparticles Using Raman Spectroscopy, Esen Efeoglu, Alan Casey, Hugh Byrne

Articles

No abstract provided.

Spectroscopic Studies Of Anthracyclines: Structural Characterization And In Vitro Tracking, Zeineb Farhane, Hugh Byrne, Malgorzata Baranska

Articles

A broad spectroscopic characterization, using ultraviolet-visible (UV-vis) and Fourier transform infrared absorption as well as Raman scattering, of two commonly used anthracyclines antibiotics (DOX) daunorubicin (DNR), their epimers (EDOX, EDNR) and ten selected analogs is presented. The paper serves as a comprehensive spectral library of UV-vis, IR and Raman spectra of anthracyclines in the solid state and in solution. The particular advantage of Raman spectroscopy for the measurement and analysis of individual antibiotics is demonstrated. Raman spectroscopy can be used to monitor the in vitro uptake and distribution of the drug in cells, using both 488 nm and 785 nm …

A Caenorhabditis Elegans Model To Detect Developmental Teratogens With Adverse Reproductive And Metabolic Effects, Alexis Ann Killeen

USF Tampa Graduate Theses and Dissertations

Obesity is a current epidemic in the United States. Greater than one third of adults and nearly one fifth of children are classified as obese (Ogden, 2014). Increased awareness of this problem has triggered interest into the potentially causal agents in our environment. These agents, termed obesogens, are a type of teratogen hypothesized to work during embryonic development by programming offspring to store excess fat. A type of teratogen, obesogens are also typically reprotoxic, affecting germline development and embryonic viability. These noxious teratogens span a variety of different chemical classes including estrogen mimics, metals and metalloids, biocides, and even voluntary …