Pharmacology, Toxicology and Environmental Health Commons^™

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …

Cd151-Α3Β1 Integrin Complexes Are Prognostic Markers Of Glioblastoma And Cooperate With Egfr To Drive Tumor Cell Motility And Invasion, Pengcheng Zhou, Sonia Erfani, Zeyi Liu, Changhe Jia, Yecang Chen, Bingwei Xu, Xinyu Deng, Jose E. Alfáro, Li Chen, Dana L. Napier, Michael Lu, Jian-An Huang, Chunming Liu, Olivier Thibault, Rosalind Segal, Binhua P. Zhou, Natasha Kyprianou, Craig Horbinski, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based …

Mercury Emissions From Coal-Fired Powerplants, Divya Gade

Environmental Management & Risk Assessment (PH 560)

Mercury is a neurotoxic heavy metal that pose a risk to the public as well as the environmental health. It is a naturally occurring element that is released into the environment from the natural or anthropogenic emissions. Among the anthropogenic emissions, coal-fired powerplants account for approximately 50 percent of the emissions because of the lack of regulations for the emissions from these facilities. The other larger sources of mercury emissions such as municipal waste combustors and medical waste incinerators are subjected to the stringent regulations thereby minimizing their total contribution. Mercury is a natural component of coal and is released …

Relationship Between Emissions Of Human Activities And Ozone Layer Depletion, Umer Murtaza

Environmental Management & Risk Assessment (PH 560)

Ozone depletion always holds an importance being a protective shield to humans and environment as well. Human activities and man-made substances are playing major role to this depletion which is increasing day by day. In this paper influence of man-made substances on ozone depletion and consequences of this depletion have been discussed. Role of chlorofluorocarbons as depleting agents is more comparatively other substances. Due to ozone depletion life on earth is affecting which are resulting different consequences like skin cancer, eye diseases and destruction of crops and aquatic life. EPA has worked a lot to save the ozone and many …

Blood Pressure Changes In Relation To Arsenic Exposure In A U.S. Pregnancy Cohort, Shohreh F. Farzan, Yu Chen, Fen Wu, Jieying Jiang, Mengling Liu, Emily Baker, Susan A. Korrick, Margaret R. Karagas

Dartmouth Scholarship

Background:

Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy.

Objectives:

We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population.

Methods:

The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which > 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by …

Mutations In The Plasmodium Falciparum Chloroquine Resistance Transporter, Pfcrt, Enlarge The Parasite's Food Vacuole And Alter Drug Sensitivities, Serena Pulcini, Henry M. Staines, Andrew H. Lee, Sarah H. Shafik, Guillaume Bouyer, Catherine M. Moore, Daniel A. Daley, Matthew J. Hoke, Lindsey M. Altenhofen, Heather J. Painter, Jianbing Mu, David J. P. Ferguson, Manuel Llinas, Rowen E. Martin, David A. Fidock, Roland Cooper, Sanjeev Krishna

Collected Faculty Scholarship

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction …

Intracellular Na+ Concentration ([Na+]I) Is Elevated In Diabetic Hearts Due To Enhanced Na+–Glucose Cotransport, Rebekah Lambert, Sarah Srodulski, Xiaoli Peng, Kenneth B. Margulies, Florin Despa, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Intracellular Na⁺ concentration ([Na⁺]i) regulates Ca²⁺ cycling, contractility, metabolism, and electrical stability of the heart. [Na⁺]i is elevated in heart failure, leading to arrhythmias and oxidative stress. We hypothesized that myocyte [Na⁺]i is also increased in type 2 diabetes (T2D) due to enhanced activity of the Na⁺-glucose cotransporter.

METHODS AND RESULTS: To test this hypothesis, we used myocardial tissue from humans with T2D and a rat model of late-onset T2D (HIP rat). Western blot analysis showed increased Na⁺-glucose cotransporter expression in failing hearts from T2D patients compared …

Nanotechnology In The Real World: Redeveloping The Nanomaterial Consumer Products Inventory, Marina E. Vance, Todd Kuiken, Eric P. Vejerano, Sean P. Mcginnis, Michael F. Hochella Jr., David Rejeski, Matthew S. Hull

Faculty Publications

To document the marketing and distribution of nano-enabled products into the commercial marketplace, the Woodrow Wilson International Center for Scholars and the Project on Emerging Nanotechnologies created the Nanotechnology Consumer Products Inventory (CPI) in 2005. The objective of this present work is to redevelop the CPI by leading a research effort to increase the usefulness and reliability of this inventory. We created eight new descriptors for consumer products, including information pertaining to the nanomaterials contained in each product. The project was motivated by the recognition that a diverse group of stakeholders from academia, industry, and state/federal government had become highly …

Lack Of Artemisinin Resistance In Plasmodium Falciparum In Uganda Based On Parasitological And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal

Collected Faculty Scholarship

We evaluated markers of artemisinin resistance in Plasmodium falciparum isolated in Kampala in 2014. By standard in vitro assays, all isolates were highly sensitive to dihydroartemisinin (DHA). By the ring-stage survival assay, after a 6-h DHA pulse, parasitemia was undetectable in 40 of 43 cultures at 72 h. Two of 53 isolates had nonsynonymous K13-propeller gene polymorphisms but did not have the mutations associated with resistance in Asia. Thus, we did not see evidence for artemisinin resistance in Uganda.

Association Between Arsenic Exposure From Drinking Water And Longitudinal Change In Blood Pressure Among Heals Cohort Participants, Jieying Jiang, Mengling Liu, Faruque Parvez, Binhuan Wang, Fen Wu, Mahbub Eunus, Sripal Bangalore, Jonathan D. Newman, Alauddin Ahmed, Tariqul Islam, Muhammed Rakibuz-Zaman, Rabiul Hasan, Golam Sarwar, Diane Levy, Vesna Slavkovich, Maria Argos, Molly Scannell Bryan, Shohreh F. Farzan, Richard B. Hayes, Joseph H. Graziano, Habibul Ahsan, Yu Chen

Dartmouth Scholarship

Background:

Cross-sectional studies have shown associations between arsenic exposure and prevalence of high blood pressure; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking.

Method:

We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every 2 years after baseline. Mixed-effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with annual change in blood pressure …

Nitric Oxide-Releasing Aspirin Suppresses Nf-Κb Signaling In Estrogen Receptor Negative Breast Cancer Cells In Vitro And In Vivo, Niharika Nath, Mitali Chattopadhyay, Deborah B. Rodes, Anna Nazarenko, Ravinder Kodela, Khosrow Kashfi

Publications and Research

Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model …

Placental Dna Methylation Related To Both Infant Toenail Mercury And Adverse Neurobehavioral Outcomes, Jennifer Zeynab Joukhadar Maccani, Devin C. Koestler, Barry Lester, E Andres Houseman, David A. Armstrong, Karl T. Kelsey, Carmen J. Marsit

Dartmouth Scholarship

Background:

Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly.

Objectives:

We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.

Methods:

The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU …

Modification Of Traffic-Related Respiratory Response By Asthma Control In A Population Of Car Commuters, Maria C. Mirabelli, Rachel Golan, Roby Greenwald, Amit U. Raysoni, Fernando Holguin, Priya Kewada, Andrea Winquist, W Dana Flanders, Jeremy A. Sarnat

School of Earth, Environmental, & Marine Sciences Faculty Publications

Background: Effects of traffic-related exposures on respiratory health are well documented, but little information is available about whether asthma control influences individual susceptibility. We analyzed data from the Atlanta Commuter Exposure study to evaluate modification of associations between rush-hour commuting, in- vehicle air pollution, and selected respiratory health outcomes by asthma control status.

Methods: Between 2009 and 2011, 39 adults participated in Atlanta Commuter Exposure, and each conducted two scripted rush-hour highway commutes. In-vehicle particulate components were measured during all commutes. Among adults with asthma, we evaluated asthma control by questionnaire and spirometry. Exhaled nitric oxide, forced expiratory volume in …

In Vitro And In Vivo Evaluation Of Infestation Deterrents Against Lice, Kyong-Sup Yoon, Jennifer K. Ketzis, Samuel W. Andrewes, Christopher S. Wu, Kris Honraet, Dorien Staljanssens, Bart Rossel, J Marshall Clark

SIUE Faculty Research, Scholarship, and Creative Activity

The human head louse is a cosmopolitan ectoparasite and frequently infests many people, particularly school-age children. Due to widespread pyrethroid resistance and the lack of efficient resistance management, there has been a considerable interest in the protection of uninfested people and prevention of reinfestation by disrupting lice transfer. In this study, two nonclinical model systems (in vitro and in vivo) were used to determine the efficacy of the infestation deterrents, Elimax lotion and Elimax shampoo, against human head lice or poultry chewing lice, respectively. With in vitro assessments, female head lice exhibited significantly higher avoidance responses to hair tufts treated …

The Associations Between Environmental Quality And Preterm Birth In The United States, 2000–2005: A Cross-Sectional Analysis, Kristen M. Rappazzo, Lynne C. Messer, Jyotsna S. Jagai, Christine L. Gray, Shannon C. Grabich, Danelle T. Lobdell

Community Health Faculty Publications and Presentations

Background: Many environmental factors have been independently associated with preterm birth (PTB). However, exposure is not isolated to a single environmental factor, but rather to many positive and negative factors that co-occur. The environmental quality index (EQI), a measure of cumulative environmental exposure across all US counties from 2000—2005, was used to investigate associations between ambient environment and PTB.

Methods: With 2000–2005 birth data from the National Center for Health Statistics for the United States (n = 24,483,348), we estimated the association between increasing quintiles of the EQI and county-level and individual-level PTB; we also considered environmental domain-specific (air, …

Iarc Monographs: 40 Years Of Evaluating Carcinogenic Hazards To Humans, Neil Pearce, Aaron Blair, Paolo Vineis, Wolfgang Ahrens, Aage Andersen, Melissa J. Perry, +Several Additional Authors

Environmental and Occupational Health Faculty Publications

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.

Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process …

The Cognition-Enhancing Effects Of Psychostimulants Involve Direct Action In The Prefrontal Cortex, Robert C. Spencer, David M. Devilbiss, Craig Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. …

Environmental And Food Allergens Reactivity And Its Association With Total Ige, Age And Gender In Karachi, Pakistan, Noreen Abbas, Ahmed Raheem, Farooq Ghani

Department of Pathology and Laboratory Medicine

Aim: The aim of this study is to assess the frequency of food and environmental allergens reactivity and its association in with age, gender and total IgE levels
Material and Methods: The study population consisted of 88 individuals including children and adults (male: 47 and female: 41). The study was conducted in the clinical laboratory, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital from May 2009 till May 2010. Sera of patients positive for total IgE were tested for allergen specific IgE levels by Immulite 2000, 3gAllergyTM. We divided allergens into two panels, namely food and environmental.
Results: …

Examining The Toxicity, Exposure, And Regulatory Approach To Potential Human Health Risks Of The Algal Toxin Domoic Acid, Thomas H. Angus

Graduate Doctoral Dissertations

Domoic acid is a neurotoxin produced by the marine diatom genus Pseudo-nitzschia and causes cell death primarily in the area of the brain responsible for long-term memory. The resulting severe illness has been termed amnesic shellfish poisoning. Domoic acid accumulates in shellfish and planktivorous fish that consume Pseudo-nitzschia, resulting in exposure to humans through consumption of planktivorous seafood. A regulatory standard in seafood was developed shortly after its discovery in 1987 to protect against acute effects. This regulatory standard has not been revised despite significant recent data in the scientific literature.

This dissertation is divided into four sections: (1) …

A Geospatial Analysis Of Norovirus Outbreaks In California, And An Investigation Of The Impact Of Environmental Variables, Alexandra Groen

Master's Projects and Capstones

Previous studies and empirical evidence suggest norovirus outbreaks in California exhibit correlation with environmental variables and exhibit spatial spread patterns. Few studies have been done looking at what causes norovirus seasonality in temperate climates and more research is needed on the regional level. This study aims to find what relationships exist with outbreak occurrence and environmental variables in California, as well as any spatial patterns of spread or clustering of outbreaks. Spatial analysis tools were used to find any relationships between California norovirus outbreak data and environmental variables. The results showed a south to north spread of outbreaks in California …

Angiotensin Ii Is Required To Induce Exaggerated Salt Sensitivity In Dahl Rats Exposed To Maternal Separation, Analia S. Loria, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

We previously reported that maternal separation, rat model of early life stress, enhances pressor responses to acute and chronic stressors. The aims of this study were to determine whether Dahl salt-sensitive (DS) rats subjected to maternal separation (MatSep-DS) as compared to normally reared DS (Ctl-DS) rats show exaggerated blood pressure responses to acute behavioral stressors, such as restraint stress or air jet stress (AJS), or, hypertensive stimuli including chronic high-salt diet (4% NaCl) and angiotensin II (AngII) infusion (200 ng/Kg/min) during 1 week. MatSep was performed in male DS rats for 3 h/day from postnatal days 2-14. At 8 weeks …

387. Gene Delivery Of Apoe2 Reduces Amyloid Pathology In Transgenic Mouse Models Of Alzheimer's Disease, Lingzhi Zhao, Andrew J. Gottesdiener, Mayur S. Parmar, Christine Grevstad, David Havlicek, Jonathan Rosenberg, Stephen Kaminsky, Maria Chiuchiolo, Dolan Sondhi, Ronald G. Crystal, Steven M. Paul

HPD Articles

The deposition of amyloid β-peptides (Aβ), cleavage products of the amyloid precursor protein (APP) by β- and γ-secretases, in brain represents a pathological hallmark of Alzheimer's disease (AD). Apolipoprotein E (APOE) ε4 allele carriers have an increased risk to develop AD and an earlier age of onset, whereas carriers of the ε2 allele have reduced risk and a delayed age of onset. APOE is also a major determinant of brain Aβ and amyloid burden in humans and in several transgenic mouse models of AD (E4>E3>E2). We have previously reported that lentivirus-mediated intraparenchymal gene delivery of APOE2 significantly reduces …

Lead Hazard Control In Henderson, Nevada: Identifying Critical Areas And The Associated Costs, Khaye Gerazel Arcilla Rufin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lead poisoning is a common, yet preventable childhood health problem in the United States today. Studies show statistically significant (p < .05) associations between higher childhood lead exposure and subsequent negative developmental outcomes. Since 1993, the U.S. Department of Housing and Urban Development (HUD) Lead Hazard Control (LHC) Grant Program has devoted more than $1 billion in funding to several cities.

This study investigated a total of n=75 homes enrolled into the Henderson Lead Hazard Control and Healthy Homes Program (HLHCHHP) from December 2013 – February 2015. A logistic regression was performed to ascertain the frequency of lead-based paint (LBP) found in homes based on the year it was constructed. Of the 75 enrolled and tested for LBP, 58 homes (77.3%) were found to contain LBP and 17 homes (22.7%) did not contain LBP. The significance value of p=0.013 shows that …

The Effect Of Red Maple Leaf Toxicosis On Reduced Glutathione Levels In Equine Erythrocytes In Vitro, Madeline A. Rohl

Undergraduate Honors Thesis Projects

Red maple leaf toxicosis is an equine blood disorder resulting from the consumption of wilted red maple (Acer rubrum L.) leaves by horses. Compounds within the leaves of red maple have oxidative effects on equine erythrocytes and can cause hemolysis of erythrocytes, the conversion of hemoglobin to methemoglobin, and the production of Heinz bodies. Reduced glutathione is important in the protection of equine erythrocytes from these oxidative events; however, in the presence of red maple toxin, glutathione is rapidly oxidized and is unavailable. The objective of this study is to determine whether the presence of vitamin C alters levels …

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 …

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 …

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 …

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 …