Pharmacology, Toxicology and Environmental Health Commons^™

Beta-Lactam Antimicrobial Dosing Optimization In Obese Patients Compared To Non-Obese Patients Using Population Pharmacokinetic/Pharmacodynamic Approach, Eun Kyoung Chung

Open Access Dissertations

Obesity is a significant global health problem and has been associated with altered pharmacokinetics and pharmacodynamics of many drugs. However, little is known regarding the effect of obesity on the pharmacokinetics and pharmacodynamics of many broad-spectrum, beta-lactam antibiotics such as piperacillin/tazobactam, meropenem, and cefepime. The objective of this study is to evaluate the population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam, meropenem, and cefepime in hospitalized obese patients in order to determine dosing regimens that provide similar exposures between obese and non-obese patients. ^ For piperacillin/tazobactam, a retrospective analysis was conducted using prospectively collected serum concentration-time data from two previous studies (Study …

Elucidation Of Pharmacologically Manipulated Responding In The Delay Discounting Task In High Alcohol Preferring Mice, Meredith Halcomb

Open Access Dissertations

Impulsive behavior is the hallmark of many psychopathologies. Uncovering the neurobiological mechanisms driving impulsivity is paramount in the development of through the delay discounting (DD) task in both human and animal models. The present study is an examination of the predictive validity of the two primary types of DD procedures in animals, the Adjusting Amounts (AA) and within session Increasing Delays (ID) tasks. Methods:Subjects were administered either1.25 mg/kg d-amphetamine (AMP), 1.5 g/kg ethanol (EtOH) or saline and tested in either the AA or ID method for 15 days to evaluate drug effects on impulsive behavior. Results: Stimulant administration resulted …

Soil Total Organic Carbon And Farmers’ Perceptions Associated With Bokashi Application In Cerro Punta, Panama, Emma Searson

Independent Study Project (ISP) Collection

Sustainable use and maintenance of agricultural soils are important for maintaining long-term agricultural productivity and environmental quality. These issues are especially important in Cerro Punta, known as the breadbasket of Panama, which is experiencing severe erosion. While current practices and agrochemical usage damage soil health and function over time, application of organic material improves soil physic-chemical properties such as nutrient and total organic carbon (TOC) content. Bokashi, a fermented organic soil amendment with effective microorganisms (EM), is thought to be especially beneficial due to its ability to augment populations of soil microbes, which deliver plant-available nutrients to crops and improve …

Waste Management And Environmental Initiatives In Accra, Ghana, Aoife Genevieve Duna

Independent Study Project (ISP) Collection

Title: Waste Management and Environmental Initiatives in Accra, Ghana

Author: Aoife Genevieve Duna ([email protected]; Middlebury College, Anthropology and Dance major)

Objective: The objective of this project was fourfold: • To study the current waste management practices by government and private waste companies • To observe the perspectives of residents on waste disposal • To explore environmental initiatives by citizens, NGOs, and student groups • To investigate the potential projects that could reduce waste

Methodology: For my project, I conducted interviews, made observations, participated in daily personal waste management, visited a landfill, and visited a composting project.

Findings: Waste collection is …

Fighting For The Right To Breathe: Exploring Perspectives Of Environmenal Threats In The South Durban Basin, Kayleigh Bhangdia

Independent Study Project (ISP) Collection

The goal of this project is to understand the way in which community members in South Durban perceive the environmental threats that they face. I have contextualized the current environmental injustices present in the wake of the Apartheid legacy. I worked closely with the South Durban Environmental Conservation Alliance in preparing my questions and conducting my interviews. I conducted 24 interviews in three different communities in the South Durban Basin including Wentworth, Merebank, and Clairwood. Following the interviews in Merebank and Clairwood, I engaged the participants in a short participatory mapping exercise in which they highlighted where the pollution was …

The Pelagic Artisanal Fishing Of Mangapwani, Northern Unguja, Shavonne Stanek

Independent Study Project (ISP) Collection

A total of 99 interviews were conducted. Over a period of 28 days from April 5- May 2, 2015, a total of 75 interviews were conducted with 72 fishermen, 2 drying processors and 1 Bwana Diko. During a 5 day preliminary period from March 12-16, 2015, a total of 24 interviews were conducted with 7 fishermen and 14 drying processors. The interviews focused on their work in the local fishing industry, the amount of fish caught and dried, and their opinions on the sustainability of their industry. The interviews were conducted using a translator who relayed the responses in English …

Hybrid Computational Toxicology Models For Regulatory Risk Assessment, Prachi Pradeep

Dissertations (1934 -)

Computational toxicology is the development of quantitative structure activity relationship (QSAR) models that relate a quantitative measure of chemical structure to a biological effect. In silico QSAR tools are widely accepted as a faster alternative to time-consuming clinical and animal testing methods for regulatory risk assessment of xenobiotics used in consumer products. However, different QSAR tools often make contrasting predictions for a new xenobiotic and may also vary in their predictive ability for different class of xenobiotics. This makes their use challenging, especially in regulatory applications, where transparency and interpretation of predictions play a crucial role in the development of …

An Evaluation Of Carbon Concentrations Associated With Biodiesel Particulate Matter In An Underground Metal Mine, David Evans

Graduate Theses & Non-Theses

Exposure to diesel particulate matter from diesel exhaust has been shown to have adverse health effects in humans. In 2012 The International Agency for Research on Cancer classified diesel exhaust as a group 1 know human carcinogen. Because of the associated health effects, there has been a strong push to reduce the amount of diesel exhaust present in the mining industry. Biodiesel is one to the more common and promising control options used to reduce the amount of diesel particulate matter that is generated during fuel combustion. The use of biodiesel over petroleum diesel has been shown to reduce not …

Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications In Apoe-/- Mice, Hasiyeti Maimaitiyiming, Kate Clemons, Qi Zhou, Heather Norman, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight …

Engineering Nanoparticles To Silence Bacterial Communication, Kristen P. Miller, Lei Wang, Yung-Pin Chen, Perry J. Pellechia, Brian C. Benicewicz, Alan W. Decho

Faculty Publications

The alarming spread of bacterial resistance to traditional antibiotics has warranted the study of alternative antimicrobial agents. Quorum sensing (QS) is a chemical cell-to-cell communication mechanism utilized by bacteria to coordinate group behaviors and establish infections. QS is integral to bacterial survival, and therefore provides a unique target for antimicrobial therapy. In this study, silicon dioxide nanoparticles (Si-NP) were engineered to target the signaling molecules [i.e., acylhomoserine lactones (HSLs)] used for QS in order to halt bacterial communication. Specifically, when Si-NP were surface functionalized with β-cyclodextrin (β-CD), then added to cultures of bacteria (Vibrio fischeri), whose luminous output depends upon …

Impact Of Antimalarial Treatment And Chemoprevention On The Drug Sensitivity Of Malaria Parasites Isolated From Ugandan Children, Patrick Tumwebaze, Melissa D. Conrad, Andrew Walakira, Norbert Leclair, Oswald Byaruhanga, Christine Nakazibwe, Benjamin Kozak, Jessica Bloome, Jaffer Okiring, Abel Kakuru, Victor Bigira, James Kapisi, Jennifer Legac, Jiri Gut, Roland A. Cooper, Moses R. Kamya, Diane V. Havlir, Grant Dorsey, Bryan Greenhouse, Samuel L. Nsobya, Philip J. Rosenthal

Collected Faculty Scholarship

Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. …

Cd47 Deficiency Protects Mice From Diet-Induced Obesity And Improves Whole Body Glucose Tolerance And Insulin Sensitivity, Hasiyeti Maimaitiyiming, Heather Norman, Qi Zhou, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were …

Increasing Expression Of Hepatitis B Surface Antigen In Maize Through Breeding, Erin Suzanne Miller

Master's Theses

The hepatitis B virus (HBV) is a common virus, with two billion people infected worldwide. It causes approximately 600,000 deaths each year, despite the availability of an effective vaccine since 1982. Maize as a platform for oral vaccination can supply a heat stable vaccine, which does not require syringes or trained personnel to administer. The Hepatitis B Surface antigen was transformed into maize and this seed was used to evaluate expression levels through the breeding process. The transgene was transferred into two elite maize inbreds by backcrossing. Highest expressing ears were selected each generation until approximately 99% commercial parent was …

Optimisation Of Isolation Methods For The Aza Group Of Marine Biotoxins And The Development Of Accurate And Precise Methods Of Analysis, Jane Kilcoyne

Doctoral

The two main groups of biotoxins which affect the Irish shellfish industry are azaspiracids (AZAs) and the okadaic acid (OA) group (OA, DTX2, DTX1 and their esters) toxins. Since AZAs were first identified in 1998, well over 30 analogues have been reported. Structural and toxicological data have been described for AZA1–5 (isolated from shellfish). LC-MS/MS is the EU reference method for detection of the AZAs (AZA1, -2 and -3) and the OA group toxins in raw shellfish with the regulatory limit set at 160 μg/kg for each toxin group. Limited supplies of purified toxins for certified reference materials (CRMs) were …

Upregulation Of Mir21 And Repression Of Grhl3 By Leptin Mediates Sinusoidal Endothelial Injury In Experimental Nonalcoholic Steatohepatitis, Sahar Pourhoseini, Ratanesh K. Seth, Suvarthi Das, Diptadip Dattaroy, Maria B. Kadiiska, Guanhua Xie, Gregory A. Michelotti, Mitzi Nagarkatti, Anna Mae Diehl, Saurabh Chatterjee

Faculty Publications

Sinusoidal endothelial dysfunction (SED) has been found to be an early event in nonalcoholic steatohepatitis (NASH) progression but the molecular mechanisms underlying its causation remains elusive. We hypothesized that adipokine leptin worsens sinusoidal injury by decreasing functionally active nitric oxide synthase 3 (NOS)3 via miR21. Using rodent models of NASH, and transgenic mice lacking leptin and leptin receptor, results showed that hyperleptinemia caused a 4-5 fold upregulation of hepatic miR21 as assessed by qRTPCR. The upregulation of miR21 led to a time-dependent repression of its target protein Grhl3 levels as shown by western blot analyses. NOS3-p/NOS3 ratio which is controlled …

Hyperbaric Oxygen Therapy Alters Vascular Reactivity Independent Of Elevations In Atp, Benjamin M. Hake, Cole Waggener, Benjamin Eovaldi, Claude Zanetti, Francis Sylvester

Peer Reviewed Articles

Hyperbaric oxygen (HBO) is a pharmacologic therapy used treat a variety of medical conditions. The underlying mechanisms of HBOs effect on vascular reactivity are poorly understood. The purpose of this study was to record the acute effects of HBO on vascular reactivity and determine the potential role of ATP in mediating these effects. Porcine mesenteric arteries were dissected and mounted in isolated organ baths to record changes in tension in response to potassium chloride (KCl, 15-60 mM), phenylephrine (PHE, 10-7-10-4 M), and sodium nitroprusside (SNP, 10-7-10-4 M) following a 2-hour exposure to HBO (1.75 ATA). HBO augmented responses to KCl …

Concomitant Uptake Of Antimicrobials And Salmonella In Soil And Into Lettuce Following Wastewater Irrigation, J. Brett Sallach, Yuping Zhang, Laurie Hodges, Daniel D. Snow, Xu Li, Shannon L. Bartelt-Hunt

Department of Civil and Environmental Engineering: Faculty Publications

The use of wastewater for irrigation may introduce antimicrobials and human pathogens into the food supply through vegetative uptake. The objective of this study was to investigate the uptake of three antimicrobials and Salmonella in two lettuce cultivars. After repeated subirrigation with synthetic wastewater, lettuce leaves and soil were collected at three sequential harvests. The internalization frequency of Salmonella in lettuce was low. A soil horizon-influenced Salmonella concentration gradient was determined with concentrations in bottom soil 2 log CFU/g higher than in top soil. Lincomycin and sulfamethoxazole were recovered from lettuce leaves at concentrations as high as 822 ng/g and …

Activation Of The Nf-Κb Pathway As A Mechanism Of Alcohol Enhanced Progression And Metastasis Of Human Hepatocellular Carcinoma, Fei Wang, Jin-Lian Yang, Ke-Ke Yu, Mei Xu, You-Zhi Xu, Li Chen, Yan-Min Lu, Hao-Shu Fang, Xin-Yi Wang, Zhong-Qian Hu, Fei-Fei Li, Lixin Kan, Jia Luo, Si-Ying Wang

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC.

METHODS AND RESULTS: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in …

Pact/Rax Regulates The Migration Of Cerebellar Granule Neurons In The Developing Cerebellum, Yue Yong, Ya Meng, Hanqing Ding, Zhiqin Fan, Yifen Tang, Chenghua Zhou, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during the postnatal development of the mouse cerebellum and its role in the migration of cerebellar granule neurons (CGNs). High expression of RAX was observed in the cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from the external granule layer (EGL) to the internal granule layer (IGL). The migration of the EGL …

The Effects Of Environmental Prompts On Stair Usage, Lori Andersen, Tim Bungum, Sheniz Moonie Phd

Nevada Journal of Public Health

Experts have advocated exercise with little success, and have turned to encouraging physical activity by incorporating it into daily activities such as taking the stairs over elevators. Much literature exists suggesting that environmental prompts can encourage the use of stairs and literature has established that some messages may be more effective than others. This study aimed to assess the effects of selected signage prompts on stair usage. Methods: Stair and elevator use were monitored in three, two-story buildings. One building served as a control, while a fitness message was placed in another building, and the final building received a weight …