Digital Commons Network^™

Store-Operated Ca(2+) Entry (Soce) Contributes To Normal Skeletal Muscle Contractility In Young But Not In Aged Skeletal Muscle, Angela M. Thornton, Xiaoli Zhao, Noah Weisleder, Leticia S. Brotto, Sylvain Bougoin, Thomas M. Nosek, Michael B. Reid, Brian Hardin, Zui Pan, Jianjie Ma, Jerome Parness, Marco Brotto

Physiology Faculty Publications

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular …

Forage News [2011-06], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• American Forage and Grassland Council Annual Meeting
• UK All Commodity Field Day
• Equine Exhibit Expanded for UK All Commodity Field Day
• Clover PowerPoint Released
• Kentucky Grazing School
• Alfalfa Intensive Training Seminar
• New Page added to Forage Website
• New Native Warm-Season Grasses Publications Available
• Filming Completed on Forage DVD
• Harvesting and Managing Flooded Forage
• Spraying Roundup Ready Alfalfa
• Net Wrap Cuts Losses, Saves Time
• Keys to a Profitable Forage Program

Role Of Phosphoinositide 3-Kinase – Akt Signaling Pathway In The Age-Related Cytokine Dysregulation In Splenic Macrophages Stimulated Via Tlr-2 Or Tlr-4 Receptors, Mosoka Papa Fallah, R. Lakshman Chelvarajan, Beth A. Garvy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Age-associated defects in both B-lymphocytes and macrophages in elderly result in a reduction in the efficacy of vaccines to many Gram positive bacteria like Streptococcus pneumoniae. Splenic macrophages from aged mice have been shown to have a defect in production of pro-inflammatory cytokines (IL-6, IL-12, IL-1β, TNF-α) but exhibit increased production of IL-10 upon TLR4 ligation. Here we showed that aged macrophages demonstrate similar cytokine dysregulation phenotype upon stimulation with TLR2 ligands, or killed S. pneumoniae. We hypothesized that an age-associated increase in activity of phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway may be playing a causal role in …

Lipid Phosphate Phosphatase 3 Enables Efficient Thymic Egress, Béatrice Bréart, Willy D. Ramos-Perez, Alejandra Mendoza, Abdelghaffar K. Salous, Michael Gobert, Yong Huang, Ralf H. Adams, Juan J. Lafaille, Diana Escalante-Alcalde, Andrew J. Morris, Susan R. Schwab

Gill Heart & Vascular Institute Faculty Publications

The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for …

Nogo-B Receptor Is Necessary For Cellular Dolichol Biosynthesis And Protein N-Glycosylation., Kenneth D Harrison, Eon Joo Park, Ningguo Gao, Andrew Kuo, Jeffrey S. Rush, Charles J Waechter, Mark A Lehrman, William C Sessa

Molecular and Cellular Biochemistry Faculty Publications

Dolichol monophosphate (Dol-P) functions as an obligate glycosyl carrier lipid in protein glycosylation reactions. Dol-P is synthesized by the successive condensation of isopentenyl diphosphate (IPP), with farnesyl diphosphate catalysed by a cis-isoprenyltransferase (cis-IPTase) activity. Despite the recognition of cis-IPTase activity 40 years ago and the molecular cloning of the human cDNA encoding the mammalian enzyme, the molecular machinery responsible for regulating this activity remains incompletely understood. Here, we identify Nogo-B receptor (NgBR) as an essential component of the Dol-P biosynthetic machinery. Loss of NgBR results in a robust deficit in cis-IPTase activity and Dol-P production, leading to diminished levels of …

Synaptic Reorganization Of Inhibitory Hilar Interneuron Circuitry After Traumatic Brain Injury In Mice, Robert F. Hunt, Stephen W. Scheff, Bret N. Smith

Physiology Faculty Publications

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found …

Forage News [2011-05], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Alfalfa Conference Photos
• 32nd Kentucky Alfalfa Conference Date Set
• Grazing Conference set for Bowling Green
• American Forage & Grassland Council Annual Meeting
• Grazing School
• Mob Grazing Misconceptions
• Letter to the Editor
• Kentucky Land Values and Rental Rates
• Economic Study Proves Value of Legumes & Non-toxic Fescue in Pastures
• Low Soil pH Reduces Fertilizer Efficiency
• Terminology for Grazing Lands and Grazing Animals

Methods And Animal Model For Analyzing Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.

Oxidative Stress Accumulates In Adipose Tissue During Aging And Inhibits Adipogenesis, Hannes M. Findeisen, Kevin J. Pearson, Florence Gizard, Yue Zhao, Hua Qing, Karrie L Jones, Dianne Cohn, Elizabeth B. Heywood, Rafael De Cabo, Dennis Bruemmer

Saha Cardiovascular Research Center Faculty Publications

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at …

Expression Stability Of Putative Reference Genes In Equine Endometrial, Testicular, And Conceptus Tissues, Claudia Klein, Josep Rutllant, Mats H. T. Troedsson

Veterinary Science Faculty Publications

BACKGROUND: Quantitative RT-PCR data are commonly normalized using a reference gene. A reference gene is a transcript which expression does not differ in the tissue of interest independent of the experimental condition. The objective of this study was to evaluate the stability of mRNA expression levels of putative reference genes in three different types of equine tissue, endometrial, testicular, and conceptus tissue.

FINDINGS: The expression stability of four (uterine tissue) and six (testicular and conceptus tissue) was assessed using descriptive data analysis and the software programs Normfinder and geNorm. In uterine samples, 18S showed the largest degree of variation in …

7 Things You Should Know About The Modern Learning Commons, Joan Lippincott, Stacey Greenwell

Library Faculty and Staff Publications

The learning commons, sometimes called an "information commons," has evolved from a combination library and computer lab into a full-service learning, research, and project space. As a place where students can meet, talk, study, and use "borrowed" equipment, the learning commons brings together the functions of libraries, labs, lounges, and seminar areas in a single community gathering place. The cost of a learning commons can be an obstacle, but for institutions that invest in a sophisticated learning commons, the new and expanded partnerships across disciplines facilitate and promote greater levels of collaboration. The commons invites students to devise their own …

Phenethyl Isothiocyanate Exhibits Antileukemic Activity In Vitro And In Vivo By Inactivation Of Akt And Activation Of Jnk Pathways, N. Gao, Amit Budhraja, S. Cheng, E.-H. Liu, J. Chen, Z. Yang, D. Chen, Zhuo Zhang, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Deep Sleep And Parietal Cortex Gene Expression Changes Are Related To Cognitive Deficits With Age, Heather M. Buechel, Jelena Popovic, James L. Searcy, Nada M. Porter, Olivier Thibault, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruption's well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep's relationship to cognitive aging.

METHODOLOGY: We measured sleep stages in young adult and aged F344 rats during inactive (enhanced sleep) and active (enhanced wake) periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken.

PRINCIPAL FINDINGS: Water maze performance was impaired, and inactive period deep sleep was decreased with age. However, increased deep sleep during the …

Obesity And Hepatosteatosis In Mice With Enhanced Oxidative Dna Damage Processing In Mitochondria, Haihong Zhang, Chenghui Xie, Horace J. Spencer, Chunlai Zuo, Masahiro Higuchi, Gouri Ranganathan, Philip A. Kern, Ming W. Chou, Qin Huang, Bartosz Szczesny, Sankar Mitra, Amanda J. Watson, Geoffrey P. Margison, Chun-Yang Fan

Clinical and Translational Science Faculty Publications

Mitochondria play critical roles in oxidative phosphorylation and energy metabolism. Increasing evidence supports that mitochondrial DNA (mtDNA) damage and dysfunction play vital roles in the development of many mitochondria-related diseases, such as obesity, diabetes mellitus, infertility, neurodegenerative disorders, and malignant tumors in humans. Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) transgenic (TG) mice were produced by nuclear microinjection. Transgene integration was analyzed by PCR. Transgene expression was measured by RT-PCR and Western blot analysis. Mitochondrial DNA damage was analyzed by mutational analyses and measurement of mtDNA copy number. Total fat content was measured by a whole-body scan using dual-energy X-ray absorptiometry. The …

Structure/Function Assessment Of Synapses At Motor Nerve Terminals, Andrew Fredericks Moser Johnstone, Kert Viele, Robin L. Cooper

Biology Faculty Publications

The release of transmitter at neuromuscular junctions (NMJ) of the opener muscle in crayfish is quantal in nature. This NMJ offers the advantage of being able to record quantal events at specific visually identified release sites, thus allowing measurement of the physiological parameters of vesicle release and its response to be directly correlated with synaptic structure.

These experiments take advantage of areas between the varicosities on the nerve terminal that we define as "stems." Stems were chosen as the region to study because of their low synaptic output due to fewer synaptic sites. Through 3D reconstruction from hundreds of serial …

Argonaute10 And Argonaute1 Regulate The Termination Of Floral Stem Cells Through Two Micrornas In Arabidopsis, Lijuan Ji, Xigang Liu, Jun Yan, Wenming Wang, Rae Eden Yumul, Yun Ju Kim, Thanh Theresa Dinh, Jun Liu, Xia Cui, Binglian Zheng, Manu Agarwal, Chunyan Liu, Xiaofeng Cao, Guiliang Tang, Xuemei Chen

Plant and Soil Sciences Faculty Publications

Stem cells are crucial in morphogenesis in plants and animals. Much is known about the mechanisms that maintain stem cell fates or trigger their terminal differentiation. However, little is known about how developmental time impacts stem cell fates. Using Arabidopsis floral stem cells as a model, we show that stem cells can undergo precise temporal regulation governed by mechanisms that are distinct from, but integrated with, those that specify cell fates. We show that two microRNAs, miR172 and miR165/166, through targeting APETALA2 and type III homeodomain-leucine zipper (HD-Zip) genes, respectively, regulate the temporal program of floral stem cells. In particular, …

P53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel Mechanism For Chemotherapy-Induced Cardiac Injury, Joyce M. Velez, Sumitra Miriyala, Ramaneeya Nithipongvanitch, Teresa Noel, Chotiros D. Plabplueng, Terry Oberley, Paiboon Jungsuwadee, Holly Van Remmen, Mary Vore, Daret K. St Clair

Toxicology and Cancer Biology Faculty Publications

The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin (DOX), a potent cancer chemotherapeutic drug. The production of ROS by DOX has been linked to DNA damage, nuclear translocation of p53, and mitochondrial injury; however, the causal relationship and molecular mechanisms underlying these events are unknown. The present study used wild-type (WT) and p53 homozygous knock-out (p53(-/-)) mice to investigate the role of p53 in the crosstalk between mitochondria and nucleus. Injecting mice with DOX (20 mg/kg) causes oxidative stress …

Differential Levels Of Glutamate Dehydrogenase 1 (Glud1) In Balb/C And C57bl/6 Mice And The Effects Of Overexpression Of The Glud1 Gene On Glutamate Release In Striatum, Kevin N. Hascup, Xiaodong Bao, Erin R. Hascup, Dongwei Hui, Wenhao Xu, Francois Pomerleau, Peter Huettl, Mary L. Michaelis, Elias K. Michaelis, Greg A. Gerhardt

Neuroscience Faculty Publications

We have previously shown that overexpression of the Glud1 (glutamate dehydrogenase 1) gene in neurons of C57BL/6 mice results in increased depolarization-induced glutamate release that eventually leads to selective neuronal injury and cell loss by 12 months of age. However, it is known that isogenic lines of Tg (transgenic) mice produced through back-crossing with one strain may differ in their phenotypic characteristics from those produced using another inbred mouse strain. Therefore, we decided to introduce the Glud1 transgene into the Balb/c strain that has endogenously lower levels of GLUD1 (glutamate dehydrogenase 1) enzyme activity in the brain as compared with …

In Vitro Amplification Of Misfolded Prion Protein Using Lysate Of Cultured Cells, Charles E. Mays, Jihyun Yeom, Hae-Eun Kang, Jifeng Bian, Vadim Khaychuk, Younghwan Kim, Jason C Bartz, Glenn C Telling, Chongsuk Ryou

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Protein misfolding cyclic amplification (PMCA) recapitulates the prion protein (PrP) conversion process under cell-free conditions. PMCA was initially established with brain material and then with further simplified constituents such as partially purified and recombinant PrP. However, availability of brain material from some species or brain material from animals with certain mutations or polymorphisms within the PrP gene is often limited. Moreover, preparation of native PrP from mammalian cells and tissues, as well as recombinant PrP from bacterial cells, involves time-consuming purification steps. To establish a convenient and versatile PMCA procedure unrestricted to the availability of substrate sources, we attempted to …

Increased Population Sampling Confirms Low Genetic Divergence Among Pteropus (Chiroptera: Pteropodidae) Fruit Bats Of Madagascar And Other Western Indian Ocean Islands, Lauren M. Chan, Steven M. Goodman, Michael D. Nowak, David W. Weisrock, Anne D. Yoder

Biology Faculty Publications

Fruit bats of the genus Pteropus occur throughout the Austral-Asian region west to islands off the eastern coast of Africa. Recent phylogenetic analyses of Pteropus from the western Indian Ocean found low sequence divergence and poor phylogenetic resolution among several morphologically defined species. We reexamine the phylogenetic relationships of these taxa by using multiple individuals per species. In addition, we estimate population genetic structure in two well-sampled taxa occurring on Madagascar and the Comoro Islands (P. rufus and P. seychellensis comorensis). Despite finding a similar pattern of low sequence divergence among species, increased sampling provides insight into the phylogeographic history …

Poster Session, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Fate of Stable Isotope Label During Predation of 15N-Tagged Wild-Type Escherichia coli by Protozoa, Ashley Barton and Alan Fryar, Dept Earth and Environmental Sciences, UK
• Cane Run Watershed Assessment and Restoration – Phase One Accomplishments, Amanda Gumbert and others, UK Cooperative Extension Service
• Improving Water Quality: Riparian Edge versus River Channel, Renee Kirtman and Kristy Hopfensperger, Biological Sciences, Northern Kentucky University
• Microscopic Population Dynamics and their Relationships to the Activated Sludge Process in a 30 MGD Wastewater Treatment Plant, Maria Lundin and David Price, LFUCG Division of Water Quality
• Southern Region Down-Well Camera Project, Glynn …

Session 2c, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Comparing the Kentucky Phosphorus Index with the P Loss Calculated with a Process-Based Model, Carl Bolster, USDA-ARS, AWMRU, Bowling Green, KY
• Kentucky Nutrient Criteria Development and Reduction Strategy, Clark Dorman, Water Quality Branch, KY DOW
• Genotypic Diversity of Escherichia coli Isolates from Environmental Sources and the Influence on Transport Behavior, Kimberly Cook and others, USDA-ARS, AWMRU, Bowling Green, KY
• A Multiparameter Approach for the Identification of Leaking and Overflowing Sanitary Sewers in the Wolf Run Watershed, Tricia Coakley and Gail Brion, Depts of Earth and Environmental Sciences and Civil Engineering, UK

Session 2b, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Building Support for Protecting and Restoring Plain, Frumpy, Dowdy Streams, Barry Tonning, Tetra Tech, Mt. Sterling, KY
• Monitoring Water Quality in Hinkston Creek: Providing Information for Action, Brian Reeder and April Haight, Center for Environmental Education, Morehead State University
• The Story of the Hinkston Creek Watershed Data, Gregory Sousa and others, Tetra Tech
• Implementation of Watershed Based Plans in the Dix River Watershed, Caroline Walz and Malissa McAlister, OSM/VISTA Dix River Watershed Coordinator and KWRRI

Session 1c, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Bush Honeysuckle Induced Aquatic Hypoxia, Stephanie Hayes and Richard Durtsche, Dept of Biological Sciences, NKU
• A Laboratory Scale, Continuous Flow Bioreactor for the Removal of Manganese in Water Supplies, Michael Snyder and Y.T. Wang, Dept of Civil Engineering, UK
• Flood Impact Due to Dam Failure: An Assessment of Current Studies and the Appropriateness of the Methodologies Applied to the Dix Dam, Allen Cantrell and Scott Yost, Dept of Civil Engineering, UK
• Development of a Comprehensive Sediment Transport Method in First Order Watersheds with Contour Coal Mining, Darren Martin and Jimmy Fox, Dept of Civil Engineering, UK

Session 1b, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Land-Use, Stream Channel Dynamics, and Macroinvertebrate Community Responses: A Northern Kentucky Case Study, Bob Hawley and others, Sustainable Streams, LLC
• Kentucky LiDAR Meets NAIP Multispectral Imagery: Toward Data Fusion in the Assessment of Watershed Change, Demetrio Zourarakis, Kentucky Div of Geographic Information, Frankfort
• Seasonal Variation in Water Quality and Dissolved Methane of Barren River Lake, John Loughrin and Carl Bolster, USDA-ARS, AWMRU, Bowling Green, KY
• Water Quality Investigation in the Eastern Kentucky Coalfields, Lisa Underwood and Lisa Hicks, USACE and KY DOW

Session 1a, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Pilot Study to Integrate Existing Karst Flow Data for Kentucky in the National Hydrography Dataset Created by the U.S. Geological Survey, Rob Blair and others, KY DOW
• An Evaluation of Physical and Chemical Discharge Parameters from a Spring that Drains the Epikarst, David Jackson, Groundwater Section, KY DOW
• Characterizing Health Risks in Privately Supplied Drinking Water Due to Agricultural Practices in Rural Western Kentucky, Leading to an Intervention Study, Karen Card and E. Glynn Beck, Dept of Epidemiology and KGS, UK
• Aqueous Geochemistry of a CO2-Enhanced Oil Recovery Project in the Sugar Creek Oil Field, Hopkins County, …

Engineered Nanomaterials: Exposures, Hazards, And Risk Prevention, Robert A. Yokel, Robert C. Macphail

Pharmaceutical Sciences Faculty Publications

Nanotechnology presents the possibility of revolutionizing many aspects of our lives. People in many settings (academic, small and large industrial, and the general public in industrialized nations) are either developing or using engineered nanomaterials (ENMs) or ENM-containing products. However, our understanding of the occupational, health and safety aspects of ENMs is still in its formative stage. A survey of the literature indicates the available information is incomplete, many of the early findings have not been independently verified, and some may have been over-interpreted. This review describes ENMs briefly, their application, the ENM workforce, the major routes of human exposure, some …

Safety And Tolerability Of An Ovine-Derived Polyclonal Anti-Tnfα Fab Fragment (Azd9773) In Patients With Severe Sepsis, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Steven G. Simonson, Gordon R. Bernard

Surgery Presentations

Sepsis remains a significant medical problem. TNFα is a central cytokine in sepsis pathophysiology. We conducted a phase IIa trial in patients with severe sepsis to assess the safety and tolerability of an intravenously infused ovine-derived polyclonal anti-TNFα Fab fragment (AZD9773).