Pharmacology, Toxicology and Environmental Health Commons^™

Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC₅₀ value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …

Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan

Articles

Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC₅₀ values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed …

Overuse Of Antibiotics In Children For Upper Respiratory Infections (Uris): A Dilemma, Malika Taufiq, Rukhsana Wamiq Zuberi

Department for Educational Development

No abstract provided.

When Curiosity Kills More Than The Cat: The Perils Of Unchecked Scientific Inquiry, Jamie Shannon

Pomona Senior Theses

This work analyzes the ecological, physical, emotional and health impacts of the US nuclear testing done in the Marshall Islands in the mid-20th century.

Mycotoxins In Grains – Causes, Prevention And Control, Hester F. Vismer

INTSORMIL Presentations

Discusses mycotoxins, their effect on grain, mitigation considerations, and resulting human toxicology.

Exhausted Or Unlicensed: Can Field-Of-Use Restrictions In Biotech License Agreements Still Prevent Off-Label Use Promotion After Quanta Computer?, Kristal M. Wicks

The University of New Hampshire Law Review

[Excerpt] “In the biotechnology (biotech) industry, companies must be increasingly aware of their intellectual property and how their licensing strategies can impact their rights. When licensing patented technology, it is common practice for biotech companies to include restricted field-of-use provisions in their license agreements. Such provisions permit a licensee to only use licensed technology in a defined field and restrict use or development in another field. This licensing strategy plays an important role within the biotech industry because it allows companies to more effectively control their intellectual property and to more efficiently research and develop pharmaceutical products.

A problem that …

Chloroquine Susceptibility And Reversibility In A Plasmodium Falciparum Genetic Cross, Jigar J. Patel, Drew Thacker, Jon C. Tan, Perri Pleeter, Lisa Checkley, Joseph M. Gonzales, Bingbing Deng, Paul D. Roepe, Roland A. Cooper, Michael T. Ferdig

Collected Faculty Scholarship

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT), are major determinants of verapamil (VP)-reversible CQ resistance (CQR). In the presence of mutant PfCRT, additional genes contribute to the wide range of CQ susceptibilities observed. It is not known if these genes influence mechanisms of chemosensitization by CQR reversal agents. Using quantitative trait locus (QTL) mapping of progeny clones from the HB3 × Dd2 cross, we show that the P. falciparum multidrug resistance gene 1 (pfmdr1) interacts with the Southeast Asiaderived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7 locus is predicted to contribute with the …

Comparison Of Bacteroides Human Markers For Pollution Diagnostics In Recreational Waters, Asli Aslan, Joan B. Rose

Environmental Health Sciences: Faculty Presentations (2010-2017)

This presentation was given during the Great Lakes Beach Association Annual Conference.

Aluminium Phosphide Poisoning: A Case Report, Shela Akbar Ali Hirani, Arshalooz Rahman

School of Nursing & Midwifery

This paper reports the case of a family in which three children were presented at Emergency Room (ER) with poisoning after the use of a pesticide at home. Initially, the cases were managed as routine cases of organophosphorus poisoning; however, the death of two children made the health team members realise that the poison's effects were delayed and devastating. Later, the compound was identified as Aluminium Phosphide (ALP), and the life of the last surviving child in the family was saved.

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …

Particle Size On Respiratory Protection Provided By Two Types Of N95 Respirators On Agricultural Settings, Jacob Cho Kyungmin, M. Susan Jones, Gordon Jones, Roy Mckay, Sergey A. Grinshpun, Alok Swivedi, Rakesh Shukla, Umesh Singh, Tiina Reponen

Nursing Faculty Publications

The objective of this study was to compare size-selective workplace protection factors (WPFs) of an N95 elastomeric respirator (ER) and an N95 filtering facepiece respirator (FFR) in agricultural environments. Twenty-five healthy farm workers ranging in age from 20 to 30 years voluntarily participated in the study. Altogether eight farms were included representing three different types: two horse farms, three pig barns, and three grain handling sites. Subjects wore the ER and FFR while performing their daily activities, such as spreading hay, feeding livestock, and shoveling. Aerosol concentrations in an optical particle size range of 0.7–10 µm were determined simultaneously inside …

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

Dissertations and Theses (Open Access)

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.

We have examined the response …

Hiv And Hepatocellular And Esophageal Carcinomas Related To Consumption Of Mycotoxin-Prone Foods In Sub-Saharan Africa, Jonathan H. Williams, Jessica A. Grubbs, Jerry W. Davis, Jia-Sheng Wang, Pauline E. Jolly, Nii-Ayi Ankrah, William O. Ellis, Evans Afriyie-Gyawu, Natalie M. Johnson, Abraham G. Robinson, Timothy D. Phillips

Environmental Health Sciences: Faculty Publications

Background: Promotion of the HIV epidemic by aflatoxin is postulated but not yet established. Sub-Saharan populations commonly consume food contaminated by mycotoxins, particularly aflatoxins (predominantly found in peanut, maize, rice, and cassava) and fumonisins, which occur primarily in maize. Aflatoxin promotes hepatocellular cancer, and fumonisin may promote esophageal cancer.

Objectives: This analysis was undertaken to test the hypotheses that consumption of mycotoxin-prone staple foods is 1) related to the incidence of HIV infection in Africa and 2) related to “signature” cancer rates confirming exposure to aflatoxins and fumonisins.

Design: World Health Organization data for causes of death and the Food …

Hypoxia And Fetal Programming Of Cardiovascular Dysfunction, Qin Xue

Loma Linda University Electronic Theses, Dissertations & Projects

Human epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of ischemic heart disease in later adult life. Of all the stresses to which the fetus is subjected, perhaps the most important and clinically relevant is that of hypoxia. The goal of this project is to test the hypothesis that chronic hypoxia during gestation adversely affects fetal cardiovascular development and impairs cardiac function in offspring. In the first part of project, we tested the hypothesis that chronic hypoxia adversely regulates contractility of fetal pulmonary arteries and veins in sheep residing at high altitude (3,801 …

A Gis Analysis Of The Environmental Variables Related To Rift Valley Fever Outbreaks, Jacqueline Florette Jackson

Health Services Research Dissertations

Rift Valley fever is a mosquito-borne disease that causes widespread febrile illness and mortality in domestic animals as well as humans (Gaff, 2007). Rift Valley fever virus was first isolated in 1931 (Daubney, 1931), and since then, outbreaks have occurred in sub-Saharan Africa, southern Africa, Egypt, Saudi Arabia, Yemen and Madagascar, proving it to be a virus able to invade ecologically diverse regions (Gaff, 2007). The potential introduction of Rift Valley fever into the United States suggests the potential for human infection and major economic disruption. It is important to understand the role environmental variables have played in historical outbreaks …

Particulate Characterization And Control Evaluation For Carbon Fiber Composite Aircraft Crash Recovery Operations, Matthew R. Ferreri

Theses and Dissertations

Within the United States Air Force (USAF) Advanced Composite Material (ACM) is gaining an increasing use in military aircraft. With the number of aircraft that have increasingly large amounts of ACM materials, the probability of an incident with one of these aircraft also increases. When such an incident occurs the aircraft needs to be disassembled, removed, and later inspected as part of the accident investigation process. This disassembly process is termed “Crash Recovery Operations.” Carbon fibers have been shown to be hazardous to human health and a pilot study raised the suspicion that nanosized aerosol may be generated during the …

A Healthy Home For Everyone: The Guide For Families And Individuals, Center For Disease Control And Prevention, Atlanta Ga

Mickey Leland Center Information Portal

The purpose of this booklet is to provide information about the connection between housing and health. You will find action steps for making your home healthy, definitions for words used in the booklet, and a resource section to find more information about a making your home a healthy home.

Bioactivity And Chemical Investigations Of Pereskia Bleo And Pereskia Grandifollia., Sim Kae Shin

Student Works (2010-2019)

Ethnopharmacological data has been one of the common useful criteria in drug discovery. Pereskia bleo and Pereskia grandifolia (Cactaceae), commonly known as ‘Jarum Tujuh Bilah’ in Malay and ‘Cak Sing Cam’ in Chinese have long been used as natural remedies in Malaysia. The experimental approach in the present study was based on bioassay-guided fractionation. The crude methanol and fractionated extracts of both Pereskia spp. were initially investigated for their biological activities such as antioxidant, antimicrobial and cytotoxic effect against five human cancer cell lines, namely nasopharyngeal epidermoid carcinoma cell line (KB), cervical carcinoma cell line (CasKi), colon carcinoma cell line …

Evaluating And Regulating Lead In Artificial Turf, Gregory Van Ulirsch, Kevin Gleason, Shawn Gerstenberger, Deaphne B. Moffett, Glenn Pulliam, Tariq Ahmed, Jerald Fagliano

Environmental & Global Health Faculty Research

Background: In 2007, a synthetic turf recreational field in Newark, New Jersey, was closed because lead was found in synthetic turf fibers and in surface dust at concentrations exceeding hazard criteria. Consequently, public health professionals across the country began testing synthetic turf to determine whether it represented a lead hazard. Currently, no standardized methods exist to test for lead in synthetic turf or to assess lead hazards.

Objectives: Our objectives were to increase awareness of potential lead exposure from synthetic turf by presenting data showing elevated lead in fibers and turf-derived dust; identify risk assessment uncertainties; recommend that federal and/or …

Studies Of Antioxidant And Angiotensin Converting Enzyme Inhibitory Activity Of Orthosiphon Stamineus (Misai Kucing)., Che Wan Imanina Che Wan Takwa

Student Works (2010-2019)

Abstract NA

Impact Of Ambient Air Pollution On Survival Of Renal Transplant Recipients, Rhonda Kristine Hwang

Loma Linda University Electronic Theses, Dissertations & Projects

There is increasing evidence that ambient air pollution is associated with coronary heart disease morbidity and mortality. This research has focused on the general public and less so on possible sensitive subgroups even though these may have even greater susceptibility to adverse effects of ambient air pollution. With highly prevalent traditional as well as nontraditional risk factors, renal transplant recipients may potentially be a sensitive subgroup. The purpose of this study was to evaluate the possible effect of between long-term exposure to air pollution on the risk of CHD mortality among renal transplant recipients. This cohort study includes 32,239 adult, …

Aerobic Fitness Does Not Modulate Protein Metabolism In Response To Increased Exercise: A Controlled Trial, Tracey J. Smith, Matthew A. Pikosky, Ann Grediagin, Carmen Castaneda-Sceppa, Lauri O. Byerley, Ellen L. Glickman, Andrew J. Young

School of Medicine Faculty Publications

BACKGROUND: A sudden increase in exercise and energy expenditure is associated with an increase in protein turnover and nitrogen excretion. This study examined how a sudden increase in exercise-induced energy expenditure affected whole body protein metabolism and nitrogen balance in people of differing levels of aerobic fitness. We hypothesized that alterations in whole-body protein turnover would be attenuated, and nitrogen balance would be preserved, in individual with higher levels of aerobic fitness. METHODS: Eleven men, categorized as either having a lower (LOW-FIT; n = 5) or higher (FIT; n = 6) aerobic fitness level, completed a 4-d baseline period (BL) …

A Comparison Of Fluoroquinolones Versus Other Antibiotics For Treating Enteric Fever: Meta-Analysis, Durrane Thaver, Anita K. M. Zaidi, Julia Critchley, Asma Azmatullah, Syed Ali Madni, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Objectives: To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever).
Design: Meta-analysis of randomised controlled trials. Data sources: Cochrane Infectious Diseases Group specialised register, CENTRAL (issue 4, 2007), Medline (1966-2007), Embase (1974-2007), LILACS (1982-2007), selected conferences, reference lists, and ongoing trial register (November 2007).
Review methods: Trials comparing fluoroquinolones with chloramphenicol, cephalosporins, or azithromycin in culture-proven enteric fever were included. Two reviewers extracted data and assessed methodological quality. Odds ratios with 95% confidence intervals were estimated. Trials recruiting over 60% children were analysed separately from trials on …

Mercury Concentrations In Muscle Tissue From Sportfish In Lake Mead, Nevada, Joanna L. Kramer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lake Mead is the largest reservoir by volume in the United States and provides fishing opportunities for numerous anglers. Considerable attention has been given to the bioaccumulation of methylmercury in fish tissues, however, no formal study utilizing approved USEPA methodology has been conducted to quantify the amount of mercury present in fish tissue from Lake Mead. The purpose of this study is to determine the concentrations of mercury present in the most commonly consumed fish from Lake Mead and to identify if any of the 4 major basins contain fish with elevated concentrations of mercury. Largemouth bass (n=49), striped bass …

Accumulation Of Artemisinin Trioxane Derivatives Within Neutral Lipids Of Plasmodium Falciparum Malaria Parasites Is Endoperoxide-Dependent, Carmony L. Hartwig, Andrew S. Rosenthal, John D'Angelo, Carol E. Griffin, Gary H. Posner, Roland A. Cooper

Collected Faculty Scholarship

The antimalarial trioxanes, exemplified by the naturally occurring sesquiterpene lactone artemisinin and its semi-synthetic derivatives, contain an endoperoxide pharmacophore that lends tremendous potency against Plasmodium parasites. Despite decades of research, their mechanism of action remains unresolved. A leading model of anti-plasmodial activity hypothesizes that iron-mediated cleavage of the endoperoxide bridge generates cytotoxic drug metabolites capable of damaging cellular macromolecules. To probe the malarial targets of the endoperoxide drugs, we studied the distribution of fluorescent dansyl trioxane derivatives in living, intraerythrocytic-stage Plasmodium falciparum parasites using microscopic imaging. The fluorescent trioxanes rapidly accumulated in parasitized erythrocytes, localizing within digestive vacuole-associated neutral lipid …

The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon

Psychiatry Faculty Publications

Rapid technological advances in genetics have created conceptual chaos regarding the genetics of drug response. Terms for differing concepts are used interchangeably: pharmacogenetics with pharmacogenomics, personalized medicine with personalized prescription. Biomarker has many definitions. The author prefers the concept of personalized prescription and uses it with implications beyond pharmacogenetics by considering all scientific information valid for prescribing medication. Genetics may not be crucial for all drugs. In this comprehensive view, clinicians must consider genetic, environmental and personal variables when prescribing medication and incorporate some basic pharmacological principles: (1) safety and efficacy, (2) pharmacokinetics and pharmacodynamics, (3) therapeutic window and prescriber's …

Mutual Information For Testing Gene-Environment Interaction, Xuesen Wu, Li Jiin, Momiao Xiong

Faculty, Staff and Student Publications

Despite current enthusiasm for investigation of gene-gene interactions and gene-environment interactions, the essential issue of how to define and detect gene-environment interactions remains unresolved. In this report, we define gene-environment interactions as a stochastic dependence in the context of the effects of the genetic and environmental risk factors on the cause of phenotypic variation among individuals. We use mutual information that is widely used in communication and complex system analysis to measure gene-environment interactions. We investigate how gene-environment interactions generate the large difference in the information measure of gene-environment interactions between the general population and a diseased population, which motives …

A Watershed Analysis Of Salmon Lake And Mcgrath Pond: Implications For Water Quality And Land Use Management, Colby Environmental Assessment Team, Colby College, Problems In Environmental Science Course (Biology 493), Colby College

Colby College Watershed Study: Salmon Lake and McGrath Pond (2009, 1993)

In the summer and fall of 2009, the Colby Environmental Assessment Team (CEAT) studied the water quality of Salmon Lake and McGrath Pond, located in the Belgrade Lakes Region of Maine. The physical, chemical and biological characteristics of water quality were measured and analyzed to evaluate the current health of these lakes. Water quality data collected during the summer and fall of 2009 were compared with data from previous years to study the historic water quality trends. Land use patterns in the Salmon/McGrath watershed were also examined to investigate their impact on the lake water quality. The water quality trends …

Group Feeding For The Lactating Cow, Anthony Joseph Martin

Dairy Science

Feeding individualized rations for lactating dairy cattle in the commercial herd based on dietary needs is a popular issue. This has been a debating topic since evolution of the Total Mixed Ration (TMR). Since dairymen were able to mix grain in a feed wagon and mix a specific dietary ration to meet the demand for an organized group, there has been an issue in which protocol cow pen grouping should take. Dairymen have always feed cattle based on if lactating or late in their gestation, nonlactating. With the evolution of the TMR dairymen are then allowed to go into more …

Ros-Mediated Oxidative Stress Influence Anti-Apoptotic Genes And Cyt C Release In Hyperglycemic Mouse Kidneys To Initiate Late Nephropathic Complications, Krina Shah, Mayur S. Parmar, Sidhartha D. Ray

HPD Articles

Decades of intense research has shown that hyperglycemiainduced ROS production can lead to a redox-imbalance causing oxidative stress (OS) in a variety of target organs in vivo. In the absence of an efficient antioxidant counteracting system, massive OS often leads to activation of stress-responsive signaling pathways resulting in deregulated expression of pro-survival and/or pro-death genes. Persistent deregulation of such pathways eventually masterminds late complications of diabetes. Most studies hold hyperglycemia-induced OS as the ‘cause’, and premature onset of apoptosis as the ‘effect’. This ‘cause and effect’ axis ultimately initiates the development and progression of macro and microvascular complications including diabetic …