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.

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 …

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.

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 …

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

Dissertations & 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 …

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, …

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

Faculty Publications

No abstract provided.

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 …

Recreational Angler Perspectives Of Nonnative Fish Species And Mercury Advisories, Christopher J. Edwards

FIU Electronic Theses and Dissertations

The central Everglades serve as a Wildlife Management Area and as a Water Conservation Area for the Miami-Fort Lauderdale metropolitan area. It is also home to over 22 nonnative freshwater fish species and carries restrictive fish consumption guidelines for Mercury. In my study, boat anglers and canal bank anglers were personally interviewed in the field, to research their awareness and perspectives of these potential environmental and health threats. The study found 78% of anglers were aware of the presence of nonnative fish species, but favored native fish species, and that 69% were aware of mercury advisories, but did not eat …

Novel Inhibitors Of Lysine Specific Demethylase 1 As Epigenetic Modulators, Michael Crowley

Michael Crowley

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 over expression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a new series of isosteres that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target …

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.

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 …

Comprehensive Forensic Toxicological Analysis Of Designer Drugs, Madeleine Jean Swortwood

FIU Electronic Theses and Dissertations

New designer drugs are constantly emerging onto the illicit drug market and it is often difficult to validate and maintain comprehensive analytical methods for accurate detection of these compounds. Generally, toxicology laboratories utilize a screening method, such as immunoassay, for the presumptive identification of drugs of abuse. When a positive result occurs, confirmatory methods, such as gas chromatography (GC) or liquid chromatography (LC) coupled with mass spectrometry (MS), are required for more sensitive and specific analyses. In recent years, the need to study the activities of these compounds in screening assays as well as to develop confirmatory techniques to detect …

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 & Occupational Health Faculty Publications

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 …

Prolactin And Fmri Response To Skf38393 In The Baboon, Brad D. Miller, Lauren A. Marks, Jonathan M. Koller, Blake J. Newman, G Larry Bretthorst, Kevin J. Black

Kevin J. Black, MD

Background: This study’s goal was to provide dose-response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select …

Iraqi Birth Defects And The Who Report, Mozhgan Savabieasfahani

Class, Race and Corporate Power

Since the U.S.-led invasion of Iraq in 2003, epidemics of birth defects and cancers are rising in many Iraqi cities. In 2012, the World Health Organization (WHO) and the Iraqi Ministry of Health (MoH) undertook a large-scale epidemiological study to determine the prevalence of birth defects in the Iraqi population. A report which appeared on the WHO website in September 2013, claims that "The rates for spontaneous abortion, stillbirths and congenital birth defects found in the [Iraq] study are consistent with or even lower than international estimates." This article discusses the severe shortcomings of this report and questions its …

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.

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.

Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski

Michael A. Rogawski

The lung provides a portal of entry that could be used to rapidly deliver anticonvulsant substances to the brain to treat seizures. In the present study, we demonstrate that midazolam, a water-soluble anticonvulsant benzodiazepine, confers potent seizure protection when administered via the intrapulmonary route. High dose (100 mg/kg) intraperitoneal midazolam induced loss-of-righting reflex in mice. Lower doses of midazolam (100–1000 μg/kg) when administered intraperitoneally did not induce loss-of-righting reflex but protected animals against pentylenetetrazol (PTZ)-induced seizures. Intrapulmonary administration of midazolam via a tracheal cannula protected against intraperitoneal PTZ seizures at lower doses. The minimal intraperitoneal and intravenous doses of midazolam …

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

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 …

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

Fisheries occasional publications

No abstract provided.

Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. Here we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully-kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-min period by convection enhanced delivery (CED). Electrographic (EEG) and behavioral …