Digital Commons Network^™

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

T-Lymphocyte Responses To Intestinally Absorbed Antigens Can Contribute To Adipose Tissue Inflammation And Glucose Intolerance During High Fat Feeding, Yuehui Wang, Jianing Li, Lihua Tang, Yu Wang, Richard Charnigo, Willem De Villiers, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue.

METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, …

Proteoglycans In Health And Disease: Novel Regulatory Signaling Mechanisms Evoked By The Small Leucine-Rich Proteoglycans., Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The small leucine-rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease. They are now being recognized as key signaling molecules with an expanding repertoire of molecular interactions affecting not only growth factors, but also various receptors involved in controlling cell growth, morphogenesis and immunity. The complexity of SLRP signaling and the multitude of affected signaling pathways can be reconciled with a hierarchical affinity-based interaction of various SLRPs in a cell- and tissue-specific context. Here, we review this interacting network, describe new relationships of the SLRPs with tyrosine kinase and Toll-like receptors and critically …

Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4⁺ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …

Polymorphisms In The Macrophage Migration Inhibitory Factor Gene And Bone Loss In Postmenopausal Women, George A. Kuchel, Anne M. Kenny

UCHC Articles - Research

Osteoporosis is a severe condition in postmenopausal women and a common cause of fracture. Osteoporosis is a complex disease with a strong genetic impact, but susceptibility is determined by many genes with modest effects and environmental factors. Only a handful of genes consistently associated with osteoporosis have been identified so far. Inflammation affects bone metabolism by interfering with the interplay between bone resorption and formation, and many inflammatory mediators are involved in natural bone remodeling. The cytokine macrophage migration inhibitory factor (MIF) has been shown to affect bone density in rodents, and polymorphisms in the human MIF promoter are associated …

Transcriptional Suppression Of Mir-29b-1/Mir-29a Promoter By C-Myc, Hedgehog, And Nf-Kappab., Justin L. Mott, Satoshi Kurita, Sophie C. Cazanave, Steven F. Bronk, Nathan W. Werneburg, Martin E. Fernandez-Zapico

Journal Articles: Biochemistry & Molecular Biology

MicroRNAs regulate pathways contributing to oncogenesis, and thus the mechanisms causing dysregulation of microRNA expression in cancer are of significant interest. Mature mir-29b levels are decreased in malignant cells, and this alteration promotes the malignant phenotype, including apoptosis resistance. However, the mechanism responsible for mir-29b suppression is unknown. Here, we examined mir-29 expression from chromosome 7q32 using cholangiocarcinoma cells as a model for mir-29b downregulation. Using 5' rapid amplification of cDNA ends, the transcriptional start site was identified for this microRNA locus. Computational analysis revealed the presence of two putative E-box (Myc-binding) sites, a Gli-binding site, and four NF-kappaB-binding sites …

Marital Behavior, Oxytocin, Vasopressin, And Wound Healing, Jean-Phillipe Gouin, Jeffrey R. Stowell, C. Sue Carter, Hossein Pournajafi-Nazarloo, Ronald Glasser, William B. Malarkey, Timothy J. Loving, Janice K. Kiecoltglaser

Faculty Research and Creative Activity

Animal studies have implicated oxytocin and vasopressin in social bonding, physiological stress responses, and wound healing. In humans, endogenous oxytocin and vasopressin levels covary with perceptions of relationship quality, marital behaviors, and physiological stress responses. To investigate relationships among marital behavior, oxytocin, vasopressin, and wound healing, and to determine the characteristics of individuals with the highest neuropeptide levels, 37 couples were admitted for a 24-hour visit in a hospital research unit. After small blister wounds were created on their forearm, couples participated in a structured social support interaction task. Blister sites were monitored daily following discharge to assess wound repair …

Prolongation Of Carrageenan-Induced Inflammation In Human Colonic Epithelial Cells By Activation Of An Nfκb-Bcl10 Loop, Alip Borthakur, Sumit Bhattacharyya, Arivarasu N. Anbazhagan, Anoop Kumar, Pradeep K. Dudeja, Joanne K. Tobacman

Clinical & Translational Sciences

Carrageenan, a sulfated polysaccharide that is widely used as a food additive, induces inflammatory responses in animal models and human cells. The carrageenan-induced inflammatory cascades involve tolllike receptor (TLR)4- and B-cell leukemia/lymphoma (BCL)10-dependent activation of NF-κB, leading to increased IL-8 production. Translocations involving BCL10 in the mucosa-associated lymphoid tissue (MALT) lymphomas are associated with constitutive activation of NF-κB. This report presents a mechanism by which carrageenan exposure leads to prolonged activation of both BCL10 and NF-κB in human colonic epithelial cells. Study findings demonstrate that nuclear RelA and RelB bind to an NF-κB binding motif in the BCL10 promoter in …

Acid-Sensing Ion Channels And Pain, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Pathophysiological conditions such as inflammation, ischemia, infection and tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggests that ASICs represent essential sensors for tissue acidosis-related pain. This review provides an update on the role of ASICs in pain sensation and discusses their therapeutic potential for pain management.

Effects Of Long-Term Pioglitazone Treatment On Peripheral And Central Markers Of Aging, Eric M. Blalock, Jeremiah T. Phelps, Tristano Pancani, James L. Searcy, Katie L. Anderson, John C. Gant, Jelena Popovic, Margarita G. Avdiushko, Don A. Cohen, Kuey-Chu Chen, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD's actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and …

Lifecourse Socioeconomic Trajectories And C-Reactive Protein Levels In Young Adults: Findings From A Brazilian Birth Cohort, Aydin Nazmi, I. O. Oliveira, Bernardo L. Horta, D. P. Gigante, Cesar G, Victora

Food Science and Nutrition

Socioeconomic factors are associated with cardiovascular disease. C-reactive protein (CRP) is increasingly implicated as a candidate linking conventional risk factors and atherosclerosis. The impact of early- and later-life socioeconomic status (SES) on CRP levels has not been widely investigated and a handful of studies from high-income countries are inconsistent. We set out to examine the associations between lifecourse socioeconomic indicators (family income at birth, maternal education, family income at age 23 and own education) on CRP levels in young adults belonging to the 1982 Pelotas (Brazil) Birth Cohort Study (n = 5914). Early-life SES showed significant and graded associations …

Bone Marrow Stromal Cells Use Tgf-Β To Suppress Allergic Responses In A Mouse Model Of Ragweed-Induced Asthma, K. Nemeth, A. Keane-Myers, J. M. Brown, D. D. Metcalfe, J. D. Gorham

Dartmouth Scholarship

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC- driven immunomodulation is mediated by the suppression of pro- inflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2- dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of …

Determination Of The Pharmacokinetics And Oral Bioavailability Of Salicylamine, A Potent Γ-Ketoaldehyde Scavenger, By Lc/Ms/Ms, Irene Zagol-Ikapitte, Elena Matafonova, Venkataraman Amarnath, Christopher L. Bodine, Olivier Boutaud, Rommel G. Tirona, John A. Oates, L. Jackson Roberts, Sean S. Davies

Paediatrics Publications

Levels of reactive γ-ketoaldehydes derived from arachidonate increase in diseases associated with inflammation and oxidative injury. To assess the biological importance of these γ-ketoaldehydes, we previously identified salicylamine as an effective γ-ketoaldehyde scavenger in vitro and in cells. To determine if salicylamine could be administered in vivo, we developed an LC/MS/MS assay to measure salicylamine in plasma and tissues. In mice, half-life (t1/2) was 62 minutes. Drinking water supplementation (1-10 g/L) generated tissue concentrations (10-500 μM) within the range previously shown to inhibit γ-ketoaldehydes in cells. Therefore, oral administration of salicylamine can be used to assess the contribution of γ-ketoaldehydes …

Deficient Cd40-Traf6 Signaling In Leukocytes Prevents Atherosclerosis By Skewing The Immune Response Toward An Antiinflammatory Profile, Esther Lutgens, Dirk Lievens, Linda Beckers, Erwin Wijnands, Oliver Soehnlein, Alma Zernecke, Tom Seijkens, David Engel, Jack Cleutjens, Anna M. Keller, Shalin H. Naike, Louis Boon, Hafid Ait Oufella, Ziad Mallat, Cory L. Ahonen, Randolph J. Noelle, Menno P. De Winther, Mat J. Daemen, Erik A. Biessen, Christian Weber

Dartmouth Scholarship

The CD40–CD40 ligand (CD40L) signaling axis plays an important role in immunological pathways. Consequently, this dyad is involved in chronic inflammatory diseases, including atherosclerosis. Inhibition of CD40L in apolipoprotein E (Apoe)–deficient ( Apoe - / - ) mice not only reduced atherosclerosis but also conferred a clinically favorable plaque phenotype that was low in inflammation and high in fibrosis. Blockade of CD40L may not be therapeutically feasible, as long-term inhibition will compromise systemic immune responses. Conceivably, more targeted intervention strategies in CD40 signaling will have less deleterious side effects. We report that deficiency in hematopoietic CD40 reduces atherosclerosis and induces …

Long Term Impact Of Neonatal Injury In Male And Female Rats: Sex Differences, Mechanisms And Clinical Implications, Jamie L. Laprairie, Anne Z. Murphy Phd

Neuroscience Institute Faculty Publications

Over the last several decades, the relative contribution of early life events to individual disease susceptibility has been explored extensively. Only fairly recently, however, has it become evident that abnormal or excessive nociceptive activity experienced during the perinatal period may permanently alter the normal development of the CNS and influence future responses to somatosensory input. Given the significant rise in the number of premature infants receiving high‐technology intensive care over the last twenty years, ex‐preterm neonates may be exceedingly vulnerable to the long‐term effects of repeated invasive interventions. The present review summarizes available clinical and laboratory findings on the lasting …

Neurotrophins Regulate Bone Marrow Stromal Cell Il-6 Expression Through The Mapk Pathway, Fariba Rezaee, Stephanie L. Relick, Giovanni Piedimonte, Stephen M. Akers, Heather A. O'Leary, Karen Martin, Michael D. Craig, Laura F. Gibson

Faculty & Staff Scholarship

Background

The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC). As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development.

Methodology/Principal Findings

In the current study we investigated BMSC …

Changes In Colon Gene Expression Associated With Increased Colon Inflammation In Interleukin-10 Gene-Deficient Mice Inoculated With Enterococcus Species, Matthew Pg Barnett, Warren C. Mcnabb, Adrian L. Cookson, Shuotun Zhu, Marcus Davy, Bianca Knoch, Katie Nones, Alison J. Hodgkinson, Nicole Roy

Illawarra Health and Medical Research Institute

Background: Inappropriate responses to normal intestinal bacteria may be involved in the development of Inflammatory Bowel Diseases (IBD, e.g. Crohn's Disease (CD), Ulcerative Colitis (UC)) and variations in the host genome may mediate this process. IL-10 gene-deficient (Il10-/-) mice develop CD-like colitis mainly in the colon, in part due to inappropriate responses to normal intestinal bacteria including Enterococcus strains, and have therefore been used as an animal model of CD. Comprehensive characterization of changes in cecum gene expression levels associated with inflammation in the Il10-/- mouse model has recently been reported. Our aim was to characterize changes in colonic gene …

Emerging Importance Of Neuron-Satellite Glia Interactions Within Trigeminal Ganglia In Craniofacial Pain, Paul L. Durham, F. G. Garrett

College of Natural and Applied Sciences

Pain in the head and face, which can be very severe and debilitating, often involves activation of trigeminal ganglion nerves. The craniofacial symptoms can manifest as acute or transient conditions such as toothaches and headaches, or can transform into more chronic conditions such as migraine, rhinosinusitis, temporomandibular joint (TMJ) disorder, or trigeminal neuralgia. Traditionally, it is known that peripheral tissue injury or inflammation leads to excitation of trigeminal nerves that release inflammatory molecules in the periphery as well as facilitate transmission of nociceptive signals to the central nervous system. However, findings from recent studies have demonstrated that peripheral tissue injury …

Inflammatory Effects Of Inhaled Sulfur Mustard In Rat Lung, Rama Malaviya, Vasanthi R. Sunil, Jessica Cervelli, Dana R. Anderson, Wesley W. Holmes, Michele L. Conti, Ronald E. Gordon, Jeffrey D. Laskin, Debra L. Laskin

US Army Research

Inhalation of sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating its cytotoxic effects are unknown and were investigated in the present studies. Male rats Crl:CD(SD) were anesthetized, and then intratracheally intubated and exposed to 0.7–1.4 mg/kg SM by vapor inhalation. Animals were euthanized 6, 24, 48 h or 7 days post-exposure and bronchoalveolar lavage fluid (BAL) and lung tissue collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including focal ulceration and detachment of the trachea and bronchial epithelia from underlying …

Combined Therapy Of Dietary Fish Oil And Stearoyl-Coa Desaturase 1 Inhibition Prevents The Metabolic Syndrome And Atherosclerosis, J. Mark Brown, Soonkyu Chung, Janet K. Sawyer, Chiara Degirolamo, Heather M. Alger, Tam M. Nguyen, Xuewei Zhu, My-Ngan Duong, Amanda L. Brown, Caleb Lord, Ramesh Shah, Matthew A. Davis, Kathryn Kelley, Martha D. Wilson, Jennifer Madenspacher, Michael B. Fessler, John S. Parks, Lawrence L. Rudel

Department of Nutrition and Health Sciences: Faculty Publications

Background—Stearoyl-CoA desaturase 1 (SCD1) is a critical regulator of energy metabolism and inflammation. We have previously reported that inhibition of SCD1 in hyperlipidemic mice fed a saturated fatty acid (SFA)-enriched diet prevented development of the metabolic syndrome, yet surprisingly promoted severe atherosclerosis. In this study we tested whether dietary fish oil supplementation could prevent the accelerated atherosclerosis caused by SCD1 inhibition.

Methods and Results—LDLr^-/-, ApoB^100/100 mice were fed diets enriched in saturated fat or fish oil in conjunction with antisense oligonucleotide (ASO) treatment to inhibit SCD1. As previously reported, in SFA-fed mice, SCD1 inhibition dramatically protected against …

Plasmid Injection And Application Of Electric Pulses Alter Endogenous Mrna And Protein Expression In B16.F10 Mouse Melanomas, L. C. Heller, Y. L. Cruz, B. Ferraro, H. Yang, R. Heller

Bioelectrics Publications

The application of electric pulses to tissues causes cell membrane destabilization, allowing exogenous molecules to enter the cells. This delivery technique can be used for plasmid gene therapy. Reporter gene expression after plasmid delivery with eight representative published protocols was compared in B16.F10 mouse melanoma tumors. This expression varied significantly based on the pulse parameters utilized for delivery. To observe the possible influence of plasmid injection and/or pulse application on endogenous gene expression, levels of stress-related mRNAs 4 and 24 h after delivery were determined by PCR array. Increases in mRNA levels for several inflammatory chemokines and cytokines were observed …