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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 | Vibrational spectra of some cyclic polysulfide 显示文摘 | Charles P Nash W Kenneth musker ADA P-J Lam | 1988 | Applied spectro-scopy1988，42，3： | 1 |
| 3 | Factors af- fecting the success of a construction project显示文摘 | ALBERT P C C DAVID S ADA P L C | 2004 | Jour- nal of Construction Engineering and Management2004，130，1： | 1 |
| 4 | Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases显示文摘 | Kara?niewicz-?ada M Danielak D Burchardt P | 2014 | Clin Pharmcokinet2014，53，2： | 1 |
| 5 | Mesenchymal stem cells can facilitate engrantment across MHC barriers and can rescue lethally irradiated recipients显示文摘 | David P Ada M Phyllis N | 2002 | Blood2002，100，11： | 1 |
| 6 | Screening ^-fructofuranosidases mutant libraries to enhance thetransglycosylation rates of /^-(2-*6) fructooligosaccharides显示文摘 | MIGUEL ADA MIGUEL A B FRANCISCO J P | 2011 | Combinatorial Chemistry and High Throughput Screening2011，14，8： | 1 |
| 7 | Acute aortic syndrome:a new look at an old conundrum显示文摘 | Vilacosta I Aragoncillo P Ca(n)adas V | | 0，，14： | 1 |
| 8 | Selection of oxygen carriers for chemical-looping combustion 显示文摘 | Ada'nez J de Diego L F Garcl'a-Labiano F Gayan P Abad A Palacios J M | 2004 | Energy Fuels2004，18，2： | 1 |
| 9 | Predicting seat belt use显示文摘 | Salzberg P Y am ada A Saibel C | 2002 | Accid Anal Prew2002，34，： | 1 |
| 10 | Factors Affecting the success of a construction project 显示文摘 | Albert P C Chan David Scott Ada P L Chan | 2004 | Journal of Construction Engineering and Management2004，130，1： | 1 |
| 11 | Evaluation of sustainability of organic,integrated and conventional farming systems:a farm and field-scale analysis显示文摘 | Cesare P Ada W Qerord G | 2003 | Agriculture Ecosystems and Environment2003，95，： | 1 |
| 12 | New serotypes of Riemerella anatipestifer isolated from ducks in Thailand 显示文摘 | Pathanasophon P Saw ada T Tanticharoenyos T | 1995 | Avian Pathology1995，24，： | 1 |
| 13 | Wireless power trans- fer to deep-tissue microimplants 显示文摘 | JOHN S H ALEXANDER J Y ADA P | 2014 | Proceedings of the National Academy of Sciences2014，111，22： | 1 |
| 14 | The immune response to influenza infection显示文摘 | Ada G L Jonds P D | 1986 | Curr Top Microbiol Immunol1986，128，： | 1 |
| 15 | Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases显示文摘 | Kara?niewicz-?ada M Danielak D Burchardt P | 2014 | Clin Pharmacokinet2014，53，2： | 1 |
| 16 | Prevalence and risk factors associated with peripheral arterial disease in the hearts of Brazil Project 显示文摘 | Makdisse M Pereira Ada C Brasil Dde P | 2008 | Arq Bras Cardiol2008，91，6： | 1 |
| 17 | Novel application of polyelectrolyte multilayers as nanoscopic closures with hermetic sealing显示文摘 | Marcott S A Ada S Gibson P | 2012 | ACS Applied Materials&Interfaces2012，4，3： | 1 |
| 18 | Acute aortic syn- drome:a new look at an old conundrum显示文摘 | Vilacosta I Aragoncillo P Ca? adas V | 2009 | Heart2009，95，14： | 1 |
| 19 | New se- rotypes of Riemerella anatipestifer isolated from ducks in Thailand 显示文摘 | Pathanasophon P Saw ada T Tanticharoenyos T | 1995 | Avian Pathology1995，24，： | 1 |
| 20 | Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases显示文摘 | Kara?niewicz-?ada M Danielak D Burchardt P | 2014 | Clin Pharmacokinet2014，53，2： | 1 |
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