Medicine and Health Sciences Commons^™

Distribution Of Culicoides Sonorensis (Diptera: Ceratopogonidae) In Nebraska, South Dakota, And North Dakota: Clarifying The Epidemiology Of Bluetongue Disease In The Northern Great Plains Region Of The United States, E. T. Schmidtmann, M. V. Herrero, A. L. Green, D. A. Dargatz, J. M. Rodriquez, T. E. Walton

Zoonotics and Wildlife Disease: Publications

The presence or absence of the biting midge Culicoides sonorensis Wirth & Jones (Diptera: Ceratopogonidae), a primary vector of bluetongue viruses (genus Orbivirus, family Reoviridae, BTV) in North America, was assessed on ranches and farms across the Northern Great Plains region of the United States, specifically Nebraska, South Dakota, and North Dakota, as part of a 2-yr regional study of BTV exposure among cattle. Blacklight/suction trap samples totaling 280 2-night intervals were taken at 140 aquatic sites (potential larval habitat for C. sonorensis) on 82 livestock operations (ranches and farms) that span a south-to-north gradient of expected decreasing …

International Federation For Emergency Medicine Model Curriculum For Medical Student Education In Emergency Medicine, Cherri Hobgood, Venkataraman Anantharaman, Glen Bandiera, Peter Cameron, Pinchas Halperin, James Holliman, Nicholas Jouriles, Darren Kilroy, Terrence Mulligan, Andrew Singer

Uniformed Services University of the Health Sciences

There is a critical and growing need for emergency physicians and emergency medicine resources worldwide. To meet this need, physicians must be trained to deliver time-sensitive interventions and life-saving emergency care. Currently, there is no internationally recognized, standard curriculum that defines the basic minimum standards for emergency medicine education. To address this lack, the International Federation for Emergency Medicine (IFEM) convened a committee of international physicians, health professionals and other experts in emergency medicine and international emergency medicine development, to outline a curriculum for foundation training of medical students in emergency medicine. This curriculum document represents the consensus of recommendations …

Incidence Of Tricyclic Antidepressant-Like Complications After Cyclobenzaprine Overdose, Vikhyat S. Bebarta, Joseph Maddry, Douglas J. Borys, David L. Morgan

Uniformed Services University of the Health Sciences

Background: The cyclobenzaprine structure is similar to amitriptyline; however, tricyclic antidepressant (TCA)-like wide complex dysrhythmia has not been reported. Our objective was to determine the incidence of TCA-like effects in cyclobenzaprine overdoses as reported to 6 poison centers for 2 years. We compared the incidence of these effects to amitriptyline overdoses collected during the same period.

Methods: We performed a retrospective review of 2 years of cases as reported to the Texas Poison Center Network. We identified sole ingestions of cyclobenzaprine and of amitriptyline. Cases had a recorded clinical outcome and clinical effect. A trained reviewer used a standard data …

Educating Clerkship Students In The Era Of Resident Duty Hour Restrictions, L. James Nixon, Meenakshy Aiyer, Steven Durning, Chris Gouveia, Jennifer R. Kogan, Valerie J. Lang, Olle Ten Cate, Karen E. Hauer

Uniformed Services University of the Health Sciences

In 2003, the Accreditation Council for Graduate Medical Education defined for the first time an upper limit on the number of hours that residents can work. This initial reduction in work hours was made with the goal of improving patient safety, resident education, and resident well-being. Now, 8 years later, further duty hour restrictions are slated to take effect July 1, 2011. These new reductions are largely a response to growing public concern about the effects of sleep deprivation on residents. Educators and residents alike have mixed opinions about the effects of prior and future duty hour restrictions on resident …

The Case For Simulation As Part Of A Comprehensive Patient Safety Program, Cynthia H. Argani, Melissa Eichelberger, Shad Deering, Andrew J. Satin

Uniformed Services University of the Health Sciences

Simulation in obstetrics allows us to practice in a safe environment. Simulations can improve the performance of individuals and obstetric teams. The evidence is overwhelming that, with simulated practice, obstetricians improve their technical and communication skills. Evidence is emerging that simulation ultimately may improve clinical outcomes. It stands to reason that simulation in obstetrics should be incorporated into comprehensive patient safety programs.

The United States Army Ocular Teleconsultation Program 2004 Through 2009, Michael J. Mines, Kraig S. Bower, Charles M. Lappan, Robert A. Mazzoli, Ronald K. Poropatich

Uniformed Services University of the Health Sciences

PURPOSE: To describe the United States Army Ocular Teleconsultation program and all consultations received from its inception in July 2004 through December 2009.

DESIGN: Retrospective, noncomparative, consecutive case series.

METHODS: All 301 consecutive ocular teleconsultations received were reviewed. The main outcome measures were differential diagnosis, evacuation recommendations, and origination of consultation. Secondary measures included patient demographics, reason for consultation, and inclusion of clinical images.

RESULTS: The average response time was 5 hours and 41 minutes. Most consultations originated from Iraq (58.8%) and Afghanistan (18.6%). Patient care-related requests accounted for 94.7% of consultations; nonphysicians submitted 26.3% of consultations. Most patients (220/285; …

Malignant Hyperthermia — Human Stress Triggering, Gerald A. Gronert, Joseph R. Tobin, Sheila Muldoon

Uniformed Services University of the Health Sciences

Letter to the Editor concerns the question of a discussion of awake porcine malignant hyperthermia that erroneously omits the awake human stress reaction of malignant hyperthermia.

How To Develop An Effective Obstetric Checklist, M. Bardett Fausett, Anthony Propst, Karin Van Doren, Benjamin T. Clark

Uniformed Services University of the Health Sciences

Checklists to guide critical procedures are becoming an increasingly important part of medical practice. These tools have proved effective in improving outcome in a variety of medical settings, including obstetrics. In this review, we outline essential principles of successful checklist creation and implementation and review our experience with checklist development in a worldwide, multiinstitutional health care delivery system.

Pre-Clinical Screening Of Immunomodulatory Compounds Using The Parent-Into-F1 Model, Charles S. Via

Uniformed Services University of the Health Sciences

Activation of the innate immune system by toll-like receptors (TLR) provides an early response to pathogens and shapes the subsequent antigen-specific adaptive immune response. Unmethylated cytosine-guanine dinucleotide (CpG)motifs present in bacterial DNA, but not vertebrate DNA, can be detected by Toll like receptor 9 (TLR9)—bearing DC and B cells resulting in a pro-inflammatory Th1 response. Synthetic oligodeoxynucleotides (ODN) expressing these CpG motifs exhibit similar in vivo biologic activity and have been shown to reduce disease severity for selected pathogens, to promote vaccine responses and to enhance anti-tumor responses (reviewed in Ref.). Conversely, suppressive DNA sequences have also been identified. TTAGGG …

Morphine-Induced Modulation Of Ltd At Gabaergic Synapses In The Ventral Tegmental Area, Matthieu Dacher, Fereshteh S. Nugent

Uniformed Services University of the Health Sciences

Adaptive behaviors often require the learning of appropriate responses to rewarding stimuli, yet aberrant learning processes can lead to serious diseases such as addiction. Dopamine (DA) neurons of the ventral tegmental area (VTA) play an essential role in the treatment of rewarding stimuli, and they exhibit plasticity in response to such stimuli, but also to drugs of abuse. Previously we discovered a form of presynaptic nitric oxide (NO)-mediated long-term potentiation (LTP_GABA) at GABAergic synapses onto VTA DA neurons that is prevented with morphine in vivo 24 h after exposure. Here we investigated whether the same GABAergic synapses are …

Anti-Fcεr1 Antibody Injections Activate Basophils And Mast Cells And Delay Type 1 Diabetes Onset In Nod Mice, Marc P. Hübner, David Larson, Marina N. Torrero, Ellen Mueller, Yinghui Shi, Kristin E. Killoran, Edward Mitre

Uniformed Services University of the Health Sciences

Mounting evidence suggests that helminth infections protect against autoimmune diseases. As helminths cause chronic IgE-mediated activation of basophils and mast cells we hypothesized that continuous activation of these cells could prevent diabetes onset in nonobese diabetic (NOD) mice in the absence of infection. Anti-FcεR1 activated basophils and mast cells and resulted in the release of IL-4 and histamine into the bloodstream. Anti-FcεR1-treated NOD mice showed a type 2 shift in insulin-specific antibody production and exhibited significant delays in diabetes onset. IL-4 responses played a partial role as the protective effect of anti-FcεR1 therapy was diminished in IL-4-deficient NOD mice. In …

Opiates And Plasticity, Matthieu Dacher, Fereshteh S. Nugent

Uniformed Services University of the Health Sciences

Opiates are among the most powerful analgesics and pain-relieving agents. However, they are potentially extremely addictive thereby limiting their medical use, making them exceedingly susceptible to abuse and adding to the global drug problem. It is believed that positive memories associated with the pleasurable effects of opiates and negative memories associated with dysphoria during opiate withdrawal contribute to compulsive opiate-seeking behavior characterizing addiction. There is a vast amount of available data regarding the neuroadaptations in response to opiates during opiate tolerance, dependence and withdrawal that contribute to opiate addiction, yet it is still a major challenge to identify the neurobiological …

Accelerated Lymphocyte Reconstitution And Long-Term Recovery After Transplantation Of Lentiviral-Transduced Rhesus Cd34+ Cells Mobilized By G-Csf And Plerixafor, Naoya Uchida, Aylin Bonifacino, Allen E. Krouse, Mark E. Metzger, Gyorgy Csako, Agnes Lee-Stroka, Ross M. Fasano, Susan F. Leitman, Joseph J. Mattapallil, Matthew M. Hsieh, John F. Tisdale, Robert E. Donahue

Uniformed Services University of the Health Sciences

Objective. Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34⁺ cells in rhesus macaques. We sought to evaluate whether these CD34⁺ cells can stably reconstitute blood cells with lentiviral gene marking.

Materials and Methods. We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34⁺ cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization.

Results. G-CSF and plerixafor mobilization resulted in CD34⁺ cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) …

Arachidonyl Trifluoromethyl Ketone Ameliorates Experimental Autoimmune Encephalomyelitis Via Blocking Peroxynitrite Formation In Mouse Spinal Cord White Matter, Adam C. Vana, Shihe Li, Rachel Ribeiro, Flaubert Tchantchou, Yumin Zhang

Uniformed Services University of the Health Sciences

Inhibition of phospholipase A₂ (PLA₂) has recently been found to attenuate the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis (MS). However, the protective mechanisms that underlie PLA₂ inhibition are still not well understood. In this study, we found that cytosolic PLA₂ (cPLA₂) was highly expressed in infiltrating lymphocytes and macrophages/microglia in mouse spinal cord white matter. Although cPLA₂ is also expressed in spinal cord neurons and oligodendrocytes, there were no differences observed in these cell types between EAE and control animals. Arachidonyl trifluoromethyl ketone (AACOCF3), …

Low-Dose Human Chorionic Gonadotropin May Improve In Vitro Fertilization Cycle Outcomes In Patients With Low Luteinizing Hormone Levels After Gonadotropin-Releasing Hormone Antagonist Administration, Anthony M. Propst, Micah J. Hill, Gordon Wright Bates, Michelle Palumbo, Anne K. Van Horne, Matthew G. Retzloff

Uniformed Services University of the Health Sciences

Objective: To evaluate the effect of low levels of endogenous luteinizing hormone (LH) and low-dose human chorionic gonadotropin (hCG) supplementation on in vitro fertilization (IVF) cycle outcomes in a gonadotropinreleasing hormone (GnRH) antagonist protocol.

Design: Retrospective study. Setting: Military medical center. Patient(s): General in vitro fertilization/embryo transfer (IVF-ET) population.

Intervention(s): Addition of low-dose urinary hCG to IVF stimulations using a recombinant follicle-stimulating hormone (FSH) and GnRH antagonist protocol. Main

Outcome Measure(s): Implantation and live-birth rates.

Result(s): As part of a larger cohort of 239 patients, 42 patients with LH levels ≤0.5 mIU/mL were evaluated. In the larger cohort, there were …

Acr Appropriateness Criteria® On Cerebrovascular Disease, Robert L. Delapaz, Franz J. Wippold Ii, Rebecca S. Cornelius, Sepideh Amin-Hanjani, Edgardo J. Angtuaco, Daniel F. Broderick, Douglas C. Brown, Jeffrey L. Creasy, Patricia C. Davis, Charles F. Garvin, Brian L. Hoh, Charles T. Mcconnell Jr, Laszlo L. Mechtler, David J. Seidenwurm, James G. Smirniotopoulos, Paul J. Tobben, Alan D. Waxman, Greg J. Zipfel

Uniformed Services University of the Health Sciences

Stroke is the sudden onset of focal neurologic symptoms due to ischemia or hemorrhage in the brain. Current FDA-approved clinical treatment of acute ischemic stroke involves the use of the intravenous thrombolytic agent recombinant tissue plasminogen activator given >3 hours after symptom onset, following the exclusion of intracerebral hemorrhage by a noncontrast CT scan. Advanced MRI, CT, and other techniques may confirm the stroke diagnosis and subtype, demonstrate lesion location, identify vascular occlusion, and guide other management decisions but, within the first 3 hours after ictus, should not delay or be used to withhold recombinant tissue plasminogen activator therapy after …

Acr Appropriateness Criteria® Chronic Chest Pain—High Probability Of Coronary Artery Disease, James P. Earls, Richard D. White, Pamela K. Woodard, Suhny Abbara, Michael K. Atalay, J. Jeffrey Carr, Linda B. Haramati, Robert C. Hendel, Vincent B. Ho, Udo Hoffman, Arfa R. Khan, Leena Mammen, Edward T. Martin, Anna Rozenshtein, Thomas Ryan, Joseph Schoeph, Robert M. Steiner, Charles S. White

Uniformed Services University of the Health Sciences

Imaging is valuable in determining the presence, extent, and severity of myocardial ischemia and the severity of obstructive coronary lesions in patients with chronic chest pain in the setting of high probability of coronary artery disease. Imaging is critical for defining patients best suited for medical therapy or intervention, and findings can be used to predict long-term prognosis and the likely benefit from various therapeutic options. Chest radiography, radionuclide single photon-emission CT, radionuclide ventriculography, and conventional coronary angiography are the imaging modalities historically used in evaluating suspected chronic myocardial ischemia. Stress echocardiography, PET, cardiac MRI, and multidetector cardiac CT have …

An Unusual Presentation Of A Right Ovarian Dermoid Cyst, Justin B. Williams, Scott C. Orr

Uniformed Services University of the Health Sciences

Dermoid cyst, or mature cystic teratoma, is the most common type of ovarian germ cell tumor. It is frequently multi-cystic, and contains sebaceous fluid as well as hair, teeth, bone, and skin. Dermoid cyst is a relatively common ovarian tumor that is an infrequent cause of abdominal and flank pain.

Book Review: Why People Get Lost: The Psychology And Neuroscience Of Spatial Cognition By Paul A. Dudchenko, Ilana R. Yurkiewicz, Jack W. Tsao

Uniformed Services University of the Health Sciences

Why People Get Lost demands no specialized knowledge of neuroscience, as its inside flap advertises. This is true to an extent; the book is an academic behemoth of research and data, but Dudchenko guides the reader through it with engaging anecdotes that inject a personal flair into the hard science. He writes with a refreshing directness, beginning each new subject with an introduction that tells the reader: this is what you are going to learn, this is how I am going to show you, and this is why you should care. If wayfinding intrigues you without preamble, it may not …

Comparison Of Combat Gauze And Traumastat In Two Severe Groin Injury Models, Françoise Arnaud, Kohsuke Teranishi, Tomoaki Okada, Dione Parreño-Sacdalan, Daniel Hupalo, George Mcnamee, Walter Carr, David Burris, Richard Mccarron

Uniformed Services University of the Health Sciences

Background. Fabric-like hemostatic dressings offer promise for hemorrhage control in noncompressible areas, especially given their similarity in form to standard gauze currently in use. Recently, two such products, Combat Gauze (CBG) and TraumaStat (TMS), were introduced. Their performance is evaluated in two vascular injury models.

Materials andMethods. The dressings were evaluated in anesthetized Yorkshire pigs, hemorrhaged by full transection of the femoral vasculature with 2 min free bleeding period (CBG = 6, TMS = 6) or by 4 mm femoral arterial puncture with 45 s free bleeding period (CBG = 8, TMS = 8). After injury, dressings were applied, followed …

Effectiveness Of Battlefield-Ethics Training During Combat Deployment: A Programme Assessment, Christopher H. Warner, George N. Appenzeller, Angela Mobbs, Jessica R. Parker, Carolynn M. Warner, Thomas Grieger, Charles W. Hoge

Uniformed Services University of the Health Sciences

Background Breakdowns in the ethical conduct of soldiers towards non-combatants on the battlefi eld are of grave concern in war. Evidence-based training approaches to prevent unethical conduct are scarce. We assessed the eff ectiveness of battlefi eld-ethics training and factors associated with unethical battlefi eld conduct.

Methods The training package, based on movie vignettes and leader-led discussions, was administered 7 to 8 months into a 15-month high-intensity combat deployment in Iraq, between Dec 11, 2007, and Jan 30, 2008. Soldiers from an infantry brigade combat team (total population about 3500) were randomly selected, on the basis of company and the …

Startle Response Related Genes, Lei Zhang, Xian-Zhang Hu, He Li, Xiaoxia Li, Stanley Smerin, David M. Benedek, Robert Ursano

Uniformed Services University of the Health Sciences

The startle reaction (also known as the startle response, the startle reflex, or the alarm reaction) is the psychological and physiological response to a sudden unexpected stimulus, such as a flash of light, a loud noise (acoustic startle reflex), or a quick movement near the face. Abnormalities of startle response have been observed in many stress-related mental disorders, such as schizophrenia and post-traumatic stress disorder (PTSD). However, the molecular mechanisms of startle in stress-associated conditions – for example, whether the startle reaction is associated with any gene variance – is still unknown. In this paper, we will carry out a …

Liposome-Induced Complement Activation And Related Cardiopulmonary Distress In Pigs: Factors Promoting Reactogenicity Of Doxil And Ambisome, János Szebeni, Péter Bedőcs, Zoltán Rozsnyay, Zsóka Weiszhár, Rudolf Urbanics, László Rosivall, Rivka Cohen, Olga Garbuzenko, György Báthori, Miklós Tóth, Rolf Bünger, Yechezkel Barenholz

Uniformed Services University of the Health Sciences

Hypersensitivity reactions to liposomal drugs, often observed with Doxil and AmBisome, can arise from activation of the complement (C) system by phospholipid bilayers. To understand the mechanism of this adverse immune reaction called C activation-related pseudoallergy (CARPA), we analyzed the relationship among liposome features, C activation in human serum in vitro, and liposome-induced cardiovascular distress in pigs, a model for human CARPA. Among the structural variables (surface charge, presence of saturated, unsaturated, and PEGylated phospholipids, and cisplatin vs. doxorubicin inside liposomes), high negative surface charge and the presence of doxorubicin were significant contributors to reactogenicity both in vitro and …

Fibroblast Growth Factor 1 (Fgfr1) Modulation Regulates Repair Capacity Of Oligodendrocyte Progenitor Cells Following Chronic Demyelination, Yong-Xing Zhou, Ravinder Pannu, Tuan Q. Le, Regina C. Armstrong

Uniformed Services University of the Health Sciences

The adult mammalian brain contains multiple populations of endogenous progenitor cell types. However, following CNS trauma or disease, the regenerative capacity of progenitor populations is typically insufficient and may actually be limited by non-permissive or inhibitory signals in the damaged parenchyma. Remyelination is the most effective and simplest regenerative process in the adult CNS yet is still insufficient following repeated or chronic demyelination. Our previous in vitro studies demonstrated that fibroblast growth factor receptor 1 (FGFR1) signaling inhibited oligodendrocyte progenitor (OP) differentiation into mature oligodendrocytes. Therefore, we questioned whether FGFR1 signaling may inhibit the capacity of OP cells to generate …

Cannabinoid Receptor Expression And Phosphorylation Are Differentially Regulated Between Male And Female Cerebellum And Brain Stem After Repeated Stress: Implication For Ptsd And Drug Abuse, Guoqiang Xing, Janis Carlton, Lei Zhang, Xiaolong Jiang, Carol Fullerton, He Li, Robert Ursano

Uniformed Services University of the Health Sciences

Recent study demonstrated a close relationship between cerebellum atrophy and symptom severity of pediatric maltreatment-related posttraumatic stress disorder (PTSD). It has also been known that females are more vulnerable than males in developing anxiety disorders after exposure to traumatic stress. The mechanisms are unknown. Because cannabinoid receptors (CB₁ and CB₂) are neuroprotective and highly expressed in the cerebellum, we investigated cerebellar CB expression in stressed rats. Young male and female Sprague-Dawley rats were given 40 unpredictable electric tail-shocks for 2 h daily on 3 consecutive days. CB₁ and CB₂ mRNA and protein levels in rat …

Valproic Acid Inhibits Neurosphere Formation By Adult Subventricular Cells By A Lithium-Sensitive Mechanism, Q. Zhou, C. L. Dalgard, C. Wynder, M. L. Doughty

Uniformed Services University of the Health Sciences

The mood stabilizer valproic acid (VPA) decreases neural progenitor proliferation and promotes neurogenesis in the adult hippocampus. However, the effects of VPA on progenitor cells in the adult subventricular zone (SVZ) are not as well characterized. Here we report VPA blocks neurosphere formation and inhibits DNA synthesis in cultured NSCs from the SVZ of adult mice. Inhibition of DNA synthesis is associated with the up-regulation of the differentiation transcription factors Egr1 and Neurod1 and down-regulation of transcription factors associated with “stemness”. Co-treatment of VPA with the mood stabilizer lithium antagonizes the anti-proliferative effects of VPA on adult NSCs and abolishes …

Distinct Role Of Nitric Oxide And Peroxynitrite In Mediating Oligodendrocyte Toxicity In Culture And In Experimental Autoimmune Encephalomyelitis, S. Li, A. C. Vana, R. Ribeiro, Y. Zhang

Uniformed Services University of the Health Sciences

Nitric oxide has been implicated in the pathogenesis of multiple sclerosis. However, it is still unclear whether nitric oxide plays a protective role or is deleterious. We have previously shown that peroxynitrite, a reaction product of nitric oxide and superoxide, is toxic to mature oligodendrocytes (OLs). The toxicity is mediated by intracellular zinc release, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), activation of 12-lipoxygenase (12-LOX) and the formation of reactive oxygen species (ROS). In this study, we found that the donors of nitric oxide, dipropylenetriamine NONOate (DPT NONOate) and diethylenetriamine NONOate (DETA NONOate), protected OLs from peroxynitrite or zinc-induced toxicity. …

Regulation Of C-Type Natriuretic Peptide Expression, Donald F. Sellitti, Nancy Koles, Maria C. Mendonça

Uniformed Services University of the Health Sciences

C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid …

Epr Measurements Of Fingernails In Q-Band, Alex Romanyukha, François Trompier, Ricardo A. Reyes, Mark A. Melanson

Uniformed Services University of the Health Sciences

Results of a feasibility study for the use of the Q-band EPR measurements of fingernails are presented. Details of the first protocol developed for Q-band (34 GHz) EPR dose measurements in fingernails and preliminary results of a dosimetry study in comparison with the commonly-used X-band (9 GHz) are reported. It was found that 1-5 mg sample mass was sufficient for EPR measurements in fingernails in the Q-band, which is significantly less than the 15-30 mg needed for the X-band. This finding makes it possible to obtain sufficient fingernail sample for dose measurements, practically from every finger of any person. Another …

In Vitro Profiling Of Epigenetic Modifications Underlying Heavy Metal Toxicity Of Tungsten-Alloy And Its Components, Ranjana Verma, Xiufen Xu, Manoj K. Jaiswal, Cara Olsen, David Mears, Giuseppina Caretti, Zygmunt Galdzicki

Uniformed Services University of the Health Sciences

Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma(SKNMC), and mousemyoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50–200 μg/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calciumchannel …