Medical Toxicology Commons^™

Comparative Cytotoxicity Study Of Nicotine And Cotinine On Mrc-5 Cell Line, Ana-Maria Vlasceanu, Daniela Luiza Baconi, Bianca Galateanu, Miriana Stan, Cristian Balalau

Journal of Mind and Medical Sciences

Nicotine has several health hazards regarding carcinogenic potential. It also imparts increased risk for respiratory, cardiovascular, and gastrointestinal disorders. Several mechanisms have been proposed for the carcinogenic potential, including effects on cell proliferation, inducing oxidative stress, DNA mutation, or inhibition of apoptosis. The cotinine metabolite is generally thought to have effects similar to nicotine in some experimental systems. The purpose of this study was to assess the nicotine and cotinine cytotoxicity on MRC-5 lung fibroblasts. The pulmonary fibroblasts were treated with various concentrations of nicotine or cotinine (in the range 1 µM – 2 mM) for 24 or 48 h and ...

Wearable Biosensors To Evaluate Recurrent Opioid Toxicity After Naloxone Administration: A Hilbert Transform Approach, Keerthi Kumar. Chintha, Premananda Indic, Brittany Chapman, Edward W. Boyer, Stephanie Carreiro

UMass Center for Clinical and Translational Science Supported Publications

Opioid abuse is a rapidly escalating problem in the United States. Effective opioid reversal is achieved with the antidote naloxone, but often does not last as long as the offending opioid, necessitating in-hospital observation. Continuous physiologic monitoring using wearable biosensors represents a potential option to extend monitoring capability outside the clinical setting across the spectrum of opioid abuse including post- naloxone administration. The present study aims to identify the physiologic change that marks the cessation of naloxone's effect. Eleven participants were recruited in the Emergency Department after naloxone administration for an opioid overdose and continuously monitored using a wearable ...

Parallelization Of A Three-Dimensional Full Multigrid Algorithm To Simulate Tumor Growth, Dylan Goodin, Chin F. Ng, Hermann B. Frieboes

Commonwealth Computational Summit

We present the performance gains of an openMP implementation of a fully adaptive nonlinear full multigrid (FMG) algorithm to simulate three-dimensional multispecies desmoplastic tumor growth on computer systems of varying processing capabilities. The FMG algorithm is applied to solve a recently published thermodynamic mixture model that uses a diffuse interface approach with fourth-order reaction-advection-diffusion PDEs (Cahn-Hilliard-type equations) that are coupled, nonlinear, and numerically stiff. The model includes multiple cell species and extracellular matrix (ECM), with adhesive and elastic energy contributions in chemical potential terms, as well as including blood and lymphatic vessels represented as continuous vasculatures. Advection-reaction-diffusion PDEs are employed ...

Chemotherapy-Induced Tissue Injury: An Insight Into The Role Of Extracellular Vesicles-Mediated Oxidative Stress Responses, Chontida Yarana, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to be instrumental to the role it plays in cardiomyopathy. Dox-induced protein oxidation changes ...

Correlation Between Preconception Maternal Non-Occupational Exposure To Interior Decoration Or Oil Paint Odour And Average Birth Weight Of Neonates: Findings From A Nationwide Cohort Study In China's Rural Areas, Huiting Liu, Shi Chen, Huijuan Zhu, Hongbo Yang, Fengying Gong, Linjie Wang, Yu Jiang, Bill Q. Lian, Chengsheng Yan, Jianqang Li, Qing Wang, Shikun Zhang, Hui Pan

Open Access Articles

BACKGROUND: Birth weight is a critical indicator of neonatal health and foretells people's health in adolescence and even adulthood. Some researchers have warned against the adverse effects on babies' birth weight of exposure to pollutants in interior decoration or oil paint by odour intake. This study evaluated the effects of maternal exposure to such factors before conception on the birth weights of neonates.

METHODS: Data on 213 461 cases in this study were from the database of the free National Pre-pregnancy Checkups Project. Defined as 'exposed' were those women exposed to oil paint odour or interior decoration at home ...

Clinical And Experimental Studies Of A Novel P525r Fus Mutation In Amyotrophic Lateral Sclerosis, Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St. Clair, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models.

Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same ...

Therapeutic Efficacy Of Cerium Oxide Nanoparticles Against Sepsis Induced Multi-Organ Dysfunction Syndrome In Sprague Dawley Rats, Nandini Durga Prasanna Kumar Manne

Nandini Manne

Sepsis is a generalized term that signifies the presence of a pathogen in the blood stream to which the body responds by eliciting a systemic inflammatory response. Although sepsis is the leading cause of death in non-coronary intensive care units in United States, there are currently no FDA approved therapeutic drugs to treat this disorder. Cerium oxide nanoparticles (CeO2) have been shown to exhibit anti-oxidant, anti-inflammatory, and anti-bacterial properties both in vitro and in vivo. Whether CeO2 nanoparticles can be used for the treatment of sepsis is currently unclear. To investigate whether CeO2 nanoparticles can be used to treat moderate ...

A Longitudinal Study Of Peripubertal Serum Organochlorine Concentrations And Semen Parameters In Young Men: The Russian Children's Study, Lidia Minguez-Alarcon, Oleg Sergeyev, Jane S. Burns, Paige L. Williams, Mary M. Lee, Susan A. Korrick, Luidmila Smigulina, Boris Revich, Russ Hauser

Mary M. Lee

BACKGROUND: Exposures to endocrine disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters.

OBJECTIVE: We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men.

METHODS: From 2003 to 2005, 516 boys were enrolled at age 8-9 years and followed for up to ten years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At age 18-19 years, 133 young men provided one or two semen samples (256 samples) collected ...

Oxycodone Ingestion Patterns In Acute Fracture Pain: A Pilot Study Using A Digital Pill, Brendan J. Innes, Peter R. Chai, Stephanie Carreiro, Brittany Chapman, Matthew Griswold, Edward W. Boyer

UMass Center for Clinical and Translational Science Research Retreat

Background: Opioids are prescribed for acute pain as needed, but no data exists on how patients take opioids after discharge from the ED. This places the onus of dosing on the patient and contributes to variable prescribing by ED physicians. ED opioid prescriptions serve as a source for unintentional exposure and contribute to the opioid epidemic. We deployed a digital pill to measure opioid ingestion patterns in individuals discharged after acute fractures.

Methods: This pilot study involved individuals without chronic opioid use (i.e. prescribed opioids > 1 week) who were discharged from the ED following acute fracture. Participants were trained ...

Analytical Testing For Marijuana, Kavita Babu

UMass Center for Clinical and Translational Science Research Retreat

As part of the mini-symposium entitled "The Problems with Marijuana and Driving: Medical, Legal, and Public Health Perspectives," Dr. Babu describes the state of the science on measurement of marijuana in the context of driving impairment.

Characterization Of A Mutant Oncolytic Adenovirus And The Role Of Jnk In Enhancing Virotherapy., Stephen L. Wechman

Electronic Theses and Dissertations

Oncolytic adenoviruses (Ads) have great therapeutic potential for lung cancer treatment. Cancer selective E1b-deleted Ads are safe; however, their clinical cancer therapeutic efficacy remains limited. The limited efficacy of Ad virotherapy is due to many factors including inefficient cancer cell lysis, Ad release and spread. Progress in overcoming these barriers to Ad virotherapy are hampered by limited knowledge of the genes associated with enhanced Ad release and spread and the dearth of understanding of the mechanisms by which E1b-deleted Ads cause cancer cell lysis. The role of c-JNK n- terminal kinase (JNK) phosphorylation in this process remains unknown ...

The Effects Of Moderate Alcohol Consumption And Inflammation On The Hepatic Matrisome And The Renal Cortex Proteome., Christine E. Dolin

Electronic Theses and Dissertations

Background. The association of chronic ethanol (EtOH) consumption with extracellular matrix (ECM) changes in alcoholic liver disease (ALD) is well established in the context of hepatic fibrosis. However, it is becoming increasingly understood that the hepatic ECM responds dynamically to stress well before fibrosis. The term “transitional tissue remodeling” describes qualitative and quantitative ECM changes in response to injury that do not alter the overall architecture of the organ; these ECM changes may contribute to early disease initiation and/or progression. The nature and magnitude of these changes to the ECM are currently poorly understood. In contrast to the liver ...

The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Importantly ...

Lkb1 Inactivation Drives Lung Cancer Lineage Switching Governed By Polycomb Repressive Complex 2, Haikuo Zhang, Christine Fillmore Brainson, Shohei Koyama, Amanda J. Redig, Ting Chen, Shuai Li, Manav Gupta, Carolina Garcia-De-Alba, Margherita Paschini, Grit S. Herter-Sprie, Gang Lu, Xin Zhang, Bryan P. Marsh, Stephanie J. Tuminello, Chunxiao Xu, Zhao Chen, Xiaoen Wang, Esra A. Akbay, Mei Zheng, Sangeetha Palakurthi, Lynette M. Sholl, Anil K. Rustgi, David J. Kwiatkowski, J. Alan Diehl, Adam J. Bass, Norman E. Sharpless, Glenn Dranoff, Peter S. Hammerman, Hongbin Ji, Nabeel Bardeesy, Dieter Saur, Hideo Watanabe, Carla F. Kim, Kwok-Kin Wong

Toxicology and Cancer Biology Faculty Publications

Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low ...

Effects Of Storage Time On Glycolysis In Donated Human Blood Units, Zhen Qi, John D. Roback, Eberhard O. Voit

Toxicology and Cancer Biology Faculty Publications

Background: Donated blood is typically stored before transfusions. During storage, the metabolism of red blood cells changes, possibly causing storage lesions. The changes are storage time dependent and exhibit donor-specific variations. It is necessary to uncover and characterize the responsible molecular mechanisms accounting for such biochemical changes, qualitatively and quantitatively; Study Design and Methods: Based on the integration of metabolic time series data, kinetic models, and a stoichiometric model of the glycolytic pathway, a customized inference method was developed and used to quantify the dynamic changes in glycolytic fluxes during the storage of donated blood units. The method provides a ...

Latexin Inactivation Enhances Survival And Long-Term Engraftment Of Hematopoietic Stem Cells And Expands The Entire Hematopoietic System In Mice, Yi Liu, Cuiping Zhang, Zhenyu Li, Chi Wang, Jianhang Jia, Tianyan Gao, Gerhard C. Hildebrandt, Daohong Zhou, Subbarao Bondada, Peng Ji, Daret K. St. Clair, Jinze Liu, Chang-Guo Zhan, Hartmut Geiger, Shuxia Wang, Ying Liang

Toxicology and Cancer Biology Faculty Publications

Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1) was a potential ...

A Novel Redox Regulator, Mntnbuoe-2-Pyp5+, Enhances Normal Hematopoietic Stem/Progenitor Cell Function, Yanming Zhao, Dustin W. Carroll, Y. You, Luksana Chaiswing, R. Wen, I. Batinic-Haberle, Subbarao Bondada, Ying Liang, Daret K. St Clair

Toxicology and Cancer Biology Faculty Publications

The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP⁵⁺(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs. Mechanistically, MnP reduces superoxide to hydrogen peroxide, which activates intracellular ...

Digital Pills To Measure Opioid Ingestion Patterns In Emergency Department Patients With Acute Fracture Pain: A Pilot Study, Peter R. Chai, Stephanie Carreiro, Brendan J. Innes, Rochelle K. Rosen, Conall O'Cleirigh, Kenneth Mayer, Edward W. Boyer

UMass Center for Clinical and Translational Science Supported Publications

BACKGROUND: Nonadherence to prescribed regimens for opioid analgesic agents contributes to increasing opioid abuse and overdose death. Opioids are frequently prescribed on an as-needed basis, placing the responsibility to determine opioid dose and frequency with the patient. There is wide variability in physician prescribing patterns because of the lack of data describing how patients actually use as-needed opioid analgesics. Digital pill systems have a radiofrequency emitter that directly measures medication ingestion events, and they provide an opportunity to discover the dose, timing, and duration of opioid therapy.

OBJECTIVE: The purpose of this study was to determine the feasibility of a ...

Nucleotide Excision Repair: Impacts Of Environmental Carcinogens And Its Role In Cancer Susceptibility In Appalachian Kentucky, Nathaniel C. Holcomb

Theses and Dissertations--Toxicology and Cancer Biology

Lung cancer is a particularly devastating disease, accounting for the most deaths among all cancer types in the United States. Despite a reduction in the country’s smoking rates, cigarette smoking remains the number one risk factor for lung cancer. Additionally arsenic exposure, which occurs primarily through contaminated drinking water in the U.S., is associated with increased lung cancer incidence. The nucleotide excision repair (NER) pathway is critical for maintenance of genomic fidelity, removing DNA lesions that could otherwise promote DNA mutations and drive carcinogenesis. Tobacco smoking introduces significant amounts of DNA damage and produces characteristic DNA mutations found ...

Changes In Mitochondrial Homeostasis And Redox Status In Astronauts Following Long Stays In Space, Hiroko P. Indo, Hideyuki J. Majima, Masahiro Terada, Shigeaki Suenaga, Kazuo Tomita, Shin Yamada, Akira Higashibata, Noriaki Ishioka, Takuro Kanekura, Ikuya Nonaka, Clare L. Hawkins, Michael J. Davies, Daret K. St Clair, Chiaki Mukai

Toxicology and Cancer Biology Faculty Publications

The effects of long-term exposure to extreme space conditions on astronauts were investigated by analyzing hair samples from ten astronauts who had spent six months on the International Space Station (ISS). Two samples were collected before, during and after their stays in the ISS; hereafter, referred to as Preflight, Inflight and Postflight, respectively. The ratios of mitochondrial (mt) to nuclear (n) DNA and mtRNA to nRNA were analyzed via quantitative PCR. The combined data of Preflight, Inflight and Postflight show a significant reduction in the mtDNA/nDNA in Inflight, and significant reductions in the mtRNA/nRNA ratios in both the ...