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| 1 | Gene expression profiling and endothelin in acute experimental pancreatitis显示文摘AIM:To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists.METHODS:Dibutyltin dichloride(DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer,biocide in agriculture,antifouling agent in paint and fabric.DBTC induces an acute pancreatitis flare through generation of reactive oxygen species.Lewis-inbred rats received a single i.v.injection with either DBTC or vehicle.Spinal cord and dorsal root ganglia(DRG) were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific genes.In a second study,groups of animals with DBTC-induced pancreatitis were treated with endothelin(ET) receptor antagonists [ET-A(BQ123) and ET-B BQ788)].Spontaneous pain related mechanical and thermal hypersensitivity were measured.Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal segments.RESULTS:Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies(edema in parenchyma,loss of pancreatic architecture and islets,infiltration of inflammatory cells,neutrophil and mononuclear cells,degeneration,vacuolization and necrosis of acinar cells) and the painrelated behaviors(cutaneous secondary mechanical and thermal hypersensitivity).Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control group.Over 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families:circulatory/acute phase/immunomodulatory;extracellular matrix;structural;channel/receptor/transporter;signaling transduction;transcription/translation-related;antioxidants/chaperones/heat shock;pancreatic and other enzymes.ET-1 was among the 52 candidate genes upregulated greater than 2-fold in animals with pancreatic inflammation and visceral pain-related behavior.Treatments with the ET-A(BQ123) and ET-B(BQ-788) antagonists revealed significant protection against inflammatory pain related mechanical and thermal hypersensitivity behaviors in animals with pancreatitis(P < 0.05).Open field spontaneous behavioral activity(at baseline,day 6 and 30 min after drug treatments(BQ123,BQ788) showed overall stable activity levels indicating that the drugs produced no undesirable effects on normal exploratory behaviors,except for a trend toward reduction of the active time and increase in resting time at the highest dose(300 μmol/L).Immunocytochemical localization revealed that expression of ET-A and ET-B receptors increased in DRG from animals with pancreatitis.Endothelin receptor localization was combined in dual staining with neuronal marker NeuN,and glia marker,glial fibrillary acidic protein.ET-A was expressed in the cell bodies and occasional nuclei of DRG neurons in na ve animals.However,phenotypic expression of ET-A receptor was greatly increased in neurons of all sizes in animals with pancreatitis.Similarly,ET-B receptor was localized in neurons and in the satellite glia,as well as in the Schwann cell glial myelin sheaths surrounding the axons passing through the DRG.CONCLUSION:Endothelin-receptor antagonists protect against inflammatory pain responses without interfering with normal exploratory behaviors.Candidate genes can serve as future biomarkers for diagnosis and/or targeted gene therapy. | Helieh S Oz Ying Lu Louis P Vera-Portocarrero Pei Ge Ada Silos-Santiago Karin N Westlund | 2012 | World Journal of Gastroenterology2012，18，32： | 6 |
| 2 | Selective RNA editing and subunit assembly of native glutamate receptors 显示文摘 | LOUIS J C BROSE N | 1994 | Neuron1994，13，1： | 1 |
| 3 | The 2007 WHO clas- sification of turnouts of the central nervous system显示文摘 | Louis D N Ohgaki H Wiestler O D | 2007 | Acta Neu- ropathol2007，114，2： | 1 |
| 4 | The 2007 WHO classifications of tumors of the central nervous system 显示文摘 | LOUIS D N OHGAKI H WIESTLER O D | 2007 | Acta Neuropathol2007，114，2： | 1 |
| 5 | Cell death and cancer: replacement of apoptotic genes and inactivation of deathsuppressor genes in therapy 显示文摘 | Favrot M Coll JL Louis N | 1998 | Gene Ther1998，5，： | 1 |
| 6 | Using real- world data tbr coverage and payment decisions: the ISPOR real- world data task force report 显示文摘 | LOUIS P G J PETER J N PENNIFER E | 2007 | Value Health2007，10，5： | 1 |
| 7 | Tracheostomal stenosis following laryngectomy显示文摘 | MYERS E N LOUIS J G | 1982 | Ann Otol Rhinol Laryngol1982，91，4： | 1 |
| 8 | The 2007 WHO classi- fication of tumours of the central nervous system显示文摘 | Louis D N Ohgaki H Wiestler O D | 2007 | Aeta Neuro- pathol2007，114，2： | 1 |
| 9 | The 2007WHO classification of tumours of the central nervous system显示文摘 | Louis D N Ohgaki H Wiestler O D | 2007 | Acta Neuro-pathol2007，114，2： | 1 |
| 10 | In Vitro and In Vivo Activities of Moxifloxacin and Clinafloxacin against Mycobacterium tuberculosis 显示文摘 | Baohong J Louis N Maslo C | 1998 | Antimicrob Agents Chemother1998，42，8： | 1 |
| 11 | Cell death and cancer: Replacement of apoptotic genes and inactivation of death suppressor genes in therapy 显示文摘 | Coll JL Louis N Negoescu A | 1998 | Gene Ther1998，5，： | 1 |
| 12 | Actuators for active flow conla'ol显示文摘 | Louis N Cattafesta L Sheplak M | 2011 | Annual Review of Fluid Mechanics2011，43，： | 1 |
| 13 | Foramen magnum syndrome secondary to calcium pyrophosphate crystal deposition in the transverse ligament of the atlas显示文摘 | Assaker R Louis E Boutry N | 2001 | Spine2001，26，12： | 1 |
| 14 | Trpcl channel mod- ulates PI3K/Akt pathway during myoblast differentiation and muscle regeneration显示文摘 | Zanou N Schakman O Louis P | 2012 | J Biol Chem2012，6，： | 1 |
| 15 | Optimising monitoring in the management of Crohn’s disease: A physician’s perspective显示文摘 | Pavol Papay Ana Ignjatovic Konstantinos Karmiris Heda Amarante Pal Milheller Brian Feagan Geert D’Haens Philippe Marteau Walter Reinisch Andreas Sturm Flavio Steinwurz Laurence Egan Julián Panés Edouard Louis Jean-Frédéric Colombel Remo Panaccione | 2013 | Journal of Crohn’s and Colitis2013，，： | 1 |
| 16 | The 2007 WHO classification of tumours of the central nervous system显示文摘 | LOUIS D N OHGAKI H WIESTLER O D | 2007 | Acta Neuropathol2007，114，2： | 1 |
| 17 | Virtual angioscopy and 3D navigation: a new technique for analysis of the aortic arch after vascular surgery 显示文摘 | Louis N Bruguiere E Kobeiter H | 2010 | Eur J Vasc Endovasc Surg2010，40，： | 1 |
| 18 | Net economic value of deer hunting in Idaho显示文摘 | Louis J N | 1986 | USDA Forest Service Resource llulhtion1986，14，2： | 1 |
| 19 | Insider trading returns and dividend signals显示文摘 | Cheng Louis T W Wallace N Davidson III Leung T Y | 2011 | International Review of Economics and Finance2011，20，： | 1 |
| 20 | The 2007 WHO classification of turnouts of the central nervous sys- tem显示文摘 | Louis D N Ohgaki H Wiestler O D | 2007 | Acta Neuropathol2007，114，2： | 1 |
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