Pharmacology, Toxicology and Environmental Health Commons^™

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Dartmouth Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.

Purifying The Human Rna-Lariat Debranching Enzyme, Ammar Saigal

Honors Program Theses and Research Projects

This project is my first official research endeavor and it involved becoming acquainted with a large variety of biochemistry and molecular biology techniques. The goal is to elucidate the structure of a protein common to most if not all cells of organisms within the Domain Eukarya, which is one of the three taxonomic domains into which all life is categorized. This is the domain most relevant to human beings as it includes plants, fungi, and animals (from a strictly biologically-taxonomic perspective, the species Homo sapiens to which you and I belong is considered belonging to the Kingdom Animalia [Animal]).

Studies On Two Polyherbal Formulations (Zpto And Zto) For Comparison Of Their Antidyslipidemic, Antihypertensive And Endothelial Modulating Activities, Nauman Aziz, Malik Hassan Mehmood, Anwarul Hassan Gilani

Department of Biological & Biomedical Sciences

Background

Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs.

Methods

To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and …

Repeated Asenapine Treatment Produces A Sensitization Effect In Two Preclinical Tests Of Antipsychotic Activity, Rongyin Qin, Yingzhu Chen, Ming Li

Department of Psychology: Faculty Publications

Among several commonly used atypical antipsychotic drugs, olanzapine and risperidone cause a sensitization effect in the conditioned avoidance response (CAR) and phencyclidine (PCP)- induced hyperlocomotion paradigms – two well established animal tests of antipsychotic drugs, whereas clozapine causes a tolerance effect. Asenapine is a novel antipsychotic drug recently approved for the treatment of schizophrenia and manic disorders. It shares several receptor binding sites and behavioral features with other atypical antipsychotic drugs. However, it is not clear what type of repeated effect (sensitization or tolerance) asenapine would induce, and whether such an effect is transferrable to other atypicals. In this study, …

Comparison Of Theophylline And 8-Cyclopentyltheophylline On The Heart Rates Of Neonatal Rats, Stephanie Arnold

Undergraduate Honors Theses

Neonatal apnea is a serious condition that affects the health of infants, especially those born prematurely. To stimulate breathing, methylxanthine drugs, such as theophylline and caffeine, are administered to reverse this condition in humans and avoid the use of breathing-assistance equipment. These drugs cause stimulation of the central nervous system and the heart, however, both detrimental side effects in preterm infants. Antagonism of adenosine receptors is the proposed mechanism of methylxanthine action. Synthetic chemists have produced xanthine analogs with increased affinity for adenosine receptors that could lead to respiratory stimulation while reducing cardiostimulant effects. For this study, theophylline and 8-cyclopentyltheophylline …

Toxic And Repellent Effects Of Pyrethroids Used In Orchards On The Honey Bee, Apis Mellifera L. (Hymenoptera: Apidae), Erin M. Ingram

Department of Entomology: Dissertations, Theses, and Student Research

Managed honey bee colonies provide valuable pollination services and are rented by fruit orchards to improve fruit quality and yield. The placement of colonies in this agricultural setting increases the possibility of exposure to pyrethroids used for broad-spectrum pest control in orchards. Although highly toxic to bees, pyrethroids are believed to pose a relatively low hazard due to their low application rates in the field as well as their contact repellent properties. Previous studies have noted a decrease in foraging visits following pyrethroid application possibly preventing bees from acquiring a lethal dose in the field.

This research quantified behaviors associated …

The Imperative Of Conserving California's Foothill Oak Woodlands, Lauren Phillips

Social Sciences

No abstract provided.

Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel

Dissertations and Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy. High levels of Bcl-2 and IAP family proteins are responsible for apoptotic-resistance and accumulation of mature CLL lymphocytes in bone-marrow, lymph nodes and peripheral blood. Besides pro-survival proteins, supporting stromal cells as well as soluble factors in the microenvironment of bone-marrow and lymph nodes provide survival advantage to CLL leukemic cells.

Though the stromal – leukemia cell interactions has been studied extensively, in-depth-knowledge on the regulation of apoptotic pathway proteins in the context of microenvironment is still limited. To address this, the first part of our study focused on comprehensive analysis of …

The Eps Matrix As An Adaptive Bastion For Biofilms: Introduction To Special Issue, Alan W. Decho

Faculty Publications

No abstract provided.

Investigation Of The Structure And Dynamics Of Regioisomeric Eu³⁺ And Gd³⁺ Chelates Of Nb-Dotma: Implications For Mri Contrast Agent Design, Benjamin Charles Webber

Dissertations and Theses

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd³⁺)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd³⁺, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of …

Importance Of Clinical Toxicology Teaching And Its Impact In Improving, Nadeem Ullah Khan, Jabeen Fayyaz, Uzma R. Khan, Asher Feroze

Department of Emergency Medicine

Objective: To assess the impact of a one-day clinical toxicology workshop in improving knowledge.
Methods: A one-day clinical toxicology workshop was conducted as a pre-conference workshop of the Annual Emergency Medicine Conference at the Aga Khan University Hospital, Karachi, in April 2012. The course was composed of poisoning-related common clinical scenarios. The pre-test and post-test understanding was used to assess the impact of the course in improving knowledge. The participants also evaluated the workshop as a whole thorough written evaluation forms. SPSS 19 was ued for statistical analysis of the data.
Result: There were 22 participants in the course. The …

Cytochrome P450 Family 1 Inhibitors And Structure-Activity Relationships, Jiawang Liu, Jayalakshmi Sridhar, Maryam Foroozesh

Faculty and Staff Publications

With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s, thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and 1B1) have been identified and studied. Generally, planar polycyclic molecules such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids are considered to potentially be effective inhibitors of these enzymes, however, the details of the structure-activity relationships and selectivity of these inhibitors are still ambiguous. In this review, we thoroughly discuss the selectivity of many representative P450 family 1 inhibitors reported in the past 20 years through a meta-analysis.

Non-Mass Transfer Limited Crystal Growth, Ryan J. Smyth, Caitlin Schram, Stephen P. Beaudoin

The Summer Undergraduate Research Fellowship (SURF) Symposium

There are many different active pharmaceutical ingredients (APIs) that have been discovered in research labs all around the world that can be used to treat and cure patients with a variety of different ailments. The challenge with these APIs in treatments is that they are not soluble in water, thus they low absorption into the blood stream (bio-availability). The key to making these APIs more bio-available is to understand how they grow as crystals and drop out of the aqueous solutions. One of the ways these APIs were made more bio-available is to render them amorphous and suspend them in …

Wash Education: Need For More Than Water Treatment For Floating Villages In Cambodia, Kevin Curry

2013 New England Association for Asian Studies Conference

Point of use (POU) water treatment systems are widely used around the world to provide microbiologically safe drinking water in developing countries. Work done in Cambodia by Brown et al. (2007) and Liang et al. (2010) have documented ceramic and biosand filters as cost effective point of use treatment systems capable of removing over 95% E. coli bacteria when properly used and maintained. Bridgewater State University and Water for Cambodia (WfC) explored using BioSand filters (BSF) to provide microbiologically safe drinking water for people in the Moat Khla floating village on the Tonle Sap Lake in Siem Reap Province. All …

Accommodations For Patients With Disabilities In Primary Care: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr

Environmental & Global Health Faculty Research

Structural barriers that limit access to health care services for people with disabilities have been identified through qualitative studies; however, little is known about how patients with disabilities are accommodated in the clinical setting when a structural barrier is encountered. The purpose of this study was to identify how primary care medical practices in the United States accommodated people with disabilities when a barrier to service is encountered. Primary care practice administrators from the medical management organization were identified through the organization’s website. Sixty-three administrators from across the US participated in this study. Practice administrators reported that patients were examined …

High Dose, Variable Length, N-Acetylcysteine (Hinac) Therapy For Late-Presenting Acetaminophen Poisoning, Jessica K. Eygnor Do, Suprina Dorai Md, Philip W. Moore Do, J Ward Donovan Md, Keith K. Burkhart Md

Department of Emergency Medicine

No abstract provided.

The Ral Exchange Factor Rgl2 Promotes Cardiomyocyte Survival And Inhibits Cardiac Fibrosis, Rebecca L. Scotland, Leah Allen, Leah J. Hennings, Ginell R. Post, Steven R. Post

Pharmacology and Nutritional Sciences Faculty Publications

Cardiomyocytes compensate to acute cardiac stress by increasing in size and contractile function. However, prolonged stress leads to a decompensated response characterized by cardiomyocyte death, tissue fibrosis and loss of cardiac function. Identifying approaches to inhibit this transition to a decompensated response may reveal important targets for treating heart failure. The Ral guanine nucleotide disassociation (RalGDS) proteins are Ras-interacting proteins that are upregulated by hypertrophic stimuli. The Ral guanine nucleotide dissociation stimulator-like 2 (Rgl2) is a member of the RalGDS family that modulates expression of hypertrophic genes in cardiomyocytes. However, the pathophysiologic consequence of increased Rgl2 expression in cardiomyoctyes remains …

Exploring New Chemotherapeutic Strategies Against Brain Cancer, Seol Kim, Anthony J. Berdis

Undergraduate Research Posters 2013

Approximately 4,000 children in the United States are diagnosed each year with a brain tumor. Brain cancers are the deadliest of all pediatric cancers as they have survival rates of less than 20%. Typical treatments include surgery and radiation therapy. However, chemotherapy is the primary therapeutic option for children, especially against aggressive brain tumors. An important chemotherapeutic agent is temozolomide, an alkylating agent that causes cell death by damaging DNA. In this project, we tested the ability of non-natural nucleosides developed in our lab in order to increase the ability of temozolomide to kill brain cancer cells. Our results show …

Curcumin-Free Turmeric Exhibits Anti-Inflammatory And Anticancer Activities: Identification Of Novel Components Of Turmeric (Abstract), Bharat Aggarwal, Wei Yuan, Shiyou Li, Subash C. Gupta

NCPC Publications and Patents

Abstract attached

Multitargeting By Turmeric, The Golden Spice: From Kitchen To Clinic (Abstract), Subash C. Gupta, Bokyung Sung, Ji Hye Kim, Sahdeo Prasad, Shiyou Li, Bharat Aggarwal

Faculty Publications

Abstract attached

West Coast Rock Lobster Fishery Ecological Risk Assessment 20 February 2013, Department Of Fisheries

Fisheries Occasional Publications

No abstract provided.

Food, Parasites, And Epidemiological Transitions: A Broad Perspective, Karl Reinhard, Luis Fernando Ferreira, Françoise Bouchet, L. Sianto, J. M.F. Dutra, A. Iniguez, Daniela Leles, M. Le Bailley, Martín Horacio Fugassa, Elisa Pucu, Adauto Araújo

Karl Reinhard Publications

Pathoecology provides unique frameworks for understanding disease transmission in ancient populations. Analyses of Old and New World archaeological samples contribute empirically to our understanding of parasite infections. Combining archaeological and anthropological data, we gain insights about health, disease, and the way ancient people lived and interacted with each other and with their environments. Here we present Old and New World parasite evidence, emphasizing how such information reflects the different ways ancient populations exploited diverse environments and became infected with zoonotic parasites. It is clear that the most common intestinal helminthes (worm endoparasites) were already infecting ancient inhabitants of the New …

Planarians Require An Intact Brain To Behaviorally React To Cocaine, But Not To React To Nicotine, Oné R. Pagán, Sean Deats, Debra Baker, Erica Montgomery, Galia Wilk, Matthew Tenaglia, Joshua Semon

Biology Faculty Publications

Planarians possess a rudimentary brain with many features in common with vertebrate brains. They also display a remarkable capacity for tissue regeneration including the complete regeneration of the nervous system. Using the induction of planarian seizure-like movements (pSLMs) as a behavioral endpoint, we demonstrate that an intact nervous system is necessary for this organism to react to cocaine exposure, but not necessary to react to nicotine administration. Decapitated planarians (Girardia tigrina) display pSLMs indistinguishable from intact worms when exposed to nicotine, but cocaine-induced pSLMs are reduced by about 95% upon decapitation. Decapitated worms recover their normal sensitivity to cocaine within …

Neurotensin And Cholecystokinin Contract Gallbladder Circular Muscle In Chickens, Teresa F. Degolier, D. R. Brown, Gary E. Duke, M. M. Palmer, J. R. Swenson, Robert E. Carraway

Biological Sciences Faculty Publications

The contractile effects of neurotensin (NT) and cholecystokinin octapeptide (CCK-8) on isolated circular smooth muscle strips of chicken gallbladder were investigated. The NT (0.25-300 nM) produced concentration-dependent contractions on smooth muscle with an EC50 of 8.5 nM (95% confidence limits = 5.3-13.6 nM). In comparison, CCK-8 produced concentration-dependent contractions with an EC50 of 13 nM (95% confidence limits of 9-20 nM). There were no statistical differences in contractile responses when comparing NT and CCK-8 at equimolar concentrations. The NT appears to act directly on smooth muscle tissue in the chicken; the contractile responses were not blocked by 10 μM atropine …

Defining The Requirements For Early Gene Expression In Bacteriophage Hk639, Amanda L. Seaton

Masters Theses & Specialist Projects

Lambdoid phages suppress transcription termination to fully express their genes. Antitermination of early gene expression in most lambdoid phages is mediated by an interaction between the N protein and a number of host-encoded factors. Bacteriophage HK022 does not rely on a protein for antitermination. To promote full expression of early phage genes, the transcripts of the HK022 put sites interact directly with RNA polymerase to convert it to a termination resistant form. Bacteriophage HK639 also uses RNA-mediated antitermination. However, it only possesses a single put-like element in its left operon. Because most lambdoid phages, including HK022, have antiterminator elements in …

Physiologically-Based Pharmacokinetic Modeling For Predicting Caffeine/Theophylline-Ciprofloxacin Interactions, David M. Ng, Ali Navid

STAR Program Research Presentations

Dynamics of interactions between the drugs caffeine, theophylline, and ciprofloxacin are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drugs are distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body are reflected in the structure and functioning of the model. Multiple drugs can interact to increase or decrease their beneficial and/or undesired effects. This is important because some common substances, such as caffeine in coffee, soft drinks, and energy drinks, are actually drugs that affect the body. Ciprofloxacin is an inhibitor of caffeine and theophylline metabolism; such inhibition …

Juxtaposing Nasa’S Aeronet Aod With Carb Pm Data Over The San Joaquin Valley To Facilitate Multi-Angle Imaging Spectroradiometer (Misr) Pm Pollution Research, John Kanemoto

STAR Program Research Presentations

Airborne particulate matter (PM) has been shown to increase the risk for asthma, chronic bronchitis, cardiopulmonary complications, and respiratory cell membrane damage/infection/leakage. PM levels are currently analyzed from two perspectives: stationary land-based monitoring (LBM) sites and total Aerosol Optical Depth (AOD) atmospheric column measurements. Both perspectives often leave miles of space between measuring locations and will have a continually increasing cost from introducing/maintaining sites. The Multi-angle Imaging SpectroRadiometer (MISR) satellite team hopes to begin investigating/archiving PM levels comprehensively via inputting MISR AOD measurements into a function/model which predicts the amount of ground level PM.

In the future, multivariable spatial correlations …

Selected Neuropharmacology Of Resurgence, Adam D. Pyszczynski

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The reemergence of problem behavior (i.e., relapse) is a key concern in most behavioral interventions. Resurgence refers to the reappearance of a previously rewarded behavior when reward for an alternative behavior is also discontinued. It is especially relevant to the reappearance of problem behavior because many behavioral interventions discontinue reward for aberrant behavior while simultaneously rewarding an appropriate response.

Understanding the underlying neuropharmacology of behavioral phenomena such as resurgence is important because it helps elucidate the neural processes at the root of such behavior, and also has implications for pharmacotherapies. Existing information about the neuropharmacology of resurgence is scarce, but …

Studies On Tracheorelaxant And Anti-Inflammatory Activities Of Rhizomes Of Polygonatum Verticillatum, Haroon Khan, Muhammad Saeed, Hassan Mehmood, Najeeb-Ur Rehman, Naveed Muhammad, Ikram-Ul Haq, Nadeem Ashraf, Kamal Eldin H El-Tahir, Anwar Gilani

Department of Biological & Biomedical Sciences

Background: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.
Methods: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the …

Aisha Bano - The Role Of Kcnq (Kv7) Potassium Channels In Schizophrenia Deficits, Aisha Bano

Ronald E. McNair Scholars Program 2013

For years, studies have been conducted to treat the positive and negative symptoms and cognitive deficits of schizophrenia; it has allowed to treat the positive symptoms through regulation of dopaminergic neurons and dopamine pathways; however, we still do not know how to treat the negative symptoms and cognitive deficits. The reason we cannot treat them is due to a lack of adequate understanding of the underlying pathology which manifests itself in the behavior. Over the years, there have been multiple proposed hypotheses regarding the underlying pathology, and accordingly, medication were developed to regulate the variety of pathways in the brain …