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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 | Social Capital and Total Factor Productivity: Evidence from Chinese Provinces显示文摘在经济开发的社会资本的影响被学者广泛地学习了。然而,在中国上下文的研究是相对稀罕的。从中国一般社会调查利用数据,我们的结果建议全部的因素生产率上的社会资本的提高的效果在中国的情况中是很有限的。社会资本的网络尺寸在分享的 OLS 评价,和信任以及社会资本的参予尺寸仅仅是重要的别越过所有评价施加影响。我们的解释是这是部分内在地由于信任,价值和标准在民用的社会形成了的事实是困难的传给市场部门。而且,当物理资本在生产起一个重要作用时,经济性能上的社会资本的影响被破坏。我们因此建议经济性能上的社会资本的效果取决于局部性的社会、经济的条件。 | Ailun Xion Hans Westlund Hongyi Li Yongjian Pu | 2017 | China & World Economy2017，25，4： | 3 |
| 3 | Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain’s pain circuitry显示文摘BACKGROUND Acute pancreatitis(AP)and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis.The validated caerulein-(CAE)induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study.AIM To determine efficacy of acetyl-L-carnitine(ALC)to reduce pain-related behaviors and brain microglial activation along the pain circuitry in CAE-pancreatitis.METHODS Pancreatitis was induced with 6 hly intraperitoneal(i.p.)injections of CAE(50μg/kg),3 d a week for 6 wk in male C57BL/6J mice.Starting in week 4,mice received either vehicle or ALC until experiment’s end.Mechanical hypersensitivity was assessed with von Frey filaments.Heat hypersensitivity was determined with the hotplate test.Anxiety-like behavior was tested in week 6 using elevated plus maze and open field tests.Microglial activation in brain was quantified histologically by immunostaining for ionized calcium-binding adaptor molecule 1(Iba1).RESULTS Mice with CAE-induced pancreatitis had significantly reduced mechanical withdrawal thresholds and heat response latencies,indicating ongoing pain.Treatment with ALC attenuated inflammation-induced hypersensitivity,but hypersensitivity due to abdominal wall injury caused by repeated intraperitoneal injections persisted.Animals with pancreatitis displayed spontaneous anxiety-like behavior in the elevated plus maze compared to controls.Treatment with ALC resulted in increased numbers of rearing activity events,but time spent in“safety”was not changed.After all the abdominal injections,pancreata were translucent if excised at experiment’s end and opaque if excised on the subsequent day,indicative of spontaneous healing.Post mortem histopathological analysis performed on pancreas sections stained with Sirius Red and Fast Green identified wide-spread fibrosis and acinar cell atrophy in sections from mice with CAE-induced pancreatitis that was not rescued by treatment with ALC.Microglial Iba1 immunostaining was significantly increased in hippocampus,thalamus(intralaminar nuclei),hypothalamus,and amygdala of mice with CAE-induced pancreatitis compared to naïve controls but unchanged in the primary somatosensory cortex compared to naïves.CONCLUSION CAE-induced pancreatitis caused increased pain-related behaviors,pancreatic fibrosis,and brain microglial changes.ALC alleviated CAE-induced mechanical and heat hypersensitivity but not abdominal wall injury-induced hypersensitivity caused by the repeated injections. | Sabrina L McIlwrath Marlene E Starr Abigail E High Hiroshi Saito Karin N Westlund | 2021 | World Journal of Gastroenterology2021，27，9： | 2 |
| 4 | Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats显示文摘AIM:To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices.METHODS:Experimental rats were fed a modified Lieber-De Carli alcohol(6%) and high-fat(65%) diet(AHF) for 10 wk while control animals received a regular rodent chow diet.Weekly behavioral tests determinedmechanical and heat sensitivity.In week 10 a fasting glucose tolerance test was performed,measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal(i.p.) injection of glucose.Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin.Pancreas sections were also stained with Sirius red and fast green to quantify collagen content.Insulinexpressing cells were identified immunohistochemically in separate sections.Tissue staining density was quantified using Image J software.After mechanical and heat sensitivity became stable(weeks 6-10) in the AHF-fed animals,three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity:a Group Ⅱ metabotropic glutamate receptor specific agonist(2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate(APDC,3 mg/kg,ip; Tocris,Bristol,United Kingdom),nociceptin(20,60,200 nmol/kg,ip; Tocris),and morphine sulfate(3 mg/kg,μ-opioid receptor agonist; Baxter Healthcare,Deerfield,IL,United States).RESULTS:Histological analysis of pancreas and liver determined that unlike control rats,AHF fed animals had pancreatic fibrosis,acinar and beta cell atrophy,with steatosis in both organs.Fat vacuolization was significantly increased in AHF fed rats(6.4% ± 1.1% in controls vs 23.8% ± 4.2%,P < 0.05).Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls(127.4 ± 9.2 mg/d L in controls vs 161.0 ± 8.6 mg/d L,P < 0.05).This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters(P < 0.05).Insulin expressing islet of Langerhans cells appeared hypertrophied while islet number and area measurements were not different from controls.Weekly behavioral tests determined that mechanical and heat sensitivities were significantly increased by 4 wk on AHF diet compared to controls.Hypersensitivitywas attenuated with efficacy similar to morphine with single dose treatment of either metabotropic glutamate receptor 2/3 agonist APDC,or nociceptin,the endogenous ligand for opioid-receptor-like 1 receptor.CONCLUSION:The AHF diet induces a chronic alcoholic pancreatitis in rats with measurable features resembling clinical patients with chronic pancreatitis and type 3c diabetes mellitus. | Sabrina L McIlwrath Karin N Westlund | 2015 | World Journal of Gastroenterology2015，21，3： | 2 |
| 5 | Fiber based optical parametric amplifiers and their applications 显示文摘 | HANSRYD J ANDREKSON P A WESTLUND M | 2002 | Journal of Selected Topics in Quantum Electronics2002，8，3： | 1 |
| 6 | Excitatory amino acid receptor involvement in peripheral nociciptive transmission in rats 显示文摘 | LAWAND N B WILLIS W D WESTLUND K N | 1997 | Eur J Pharmacol1997，324，23： | 1 |
| 7 | High-Perfor- mance Optical-Fiber-Nonlinearity-Based Optical Waveform Monitoring 显示文摘 | WESTLUND M ANDREKSON A SUNNERUD H | 2005 | IEEE Journal of Lightwave Technology2005，23，6： | 1 |
| 8 | Measuring environmental impact on society in the EFQM system显示文摘 | Westlund A H | 2001 | Total Quality Management2001，12，1： | 1 |
| 9 | Local Social Capital and Entrepreneurship显示文摘 | Hans Westlund Roger Bolton | 2003 | Small Business Economics2003，，2： | 1 |
| 10 | Descending projections of the locus coeruleus and subeoeruleus/medial parabrachial nu clei in monkey: axonal transport studies and dopamine- betahydroxylase immunocytoehemistry 显示文摘 | Westlund KN Coulter JD | 1980 | Brain Res1980，2，3： | 1 |
| 11 | Neuroanatomy of the pain system and of the pathways that modulate pain 显示文摘 | Willis WD Westlund KN | 1997 | J Clin NeuroPhysiol1997，14，： | 1 |
| 12 | Calcitonin gene-related peptide containing primary afferent fibers synapse on primate spinothalamic tract cells显示文摘 | Westlund KN Zhang D Sorkin LS | 1990 | Neurosci Lett1990，109，： | 1 |
| 13 | Chronic inflammation and pain in a tumor necrosis factor receptor (TNFR) (p55/p75-/-) dual deficient murine model显示文摘 | Karin N. Westlund Liping Zhang Fei Ma Helieh S. Oz | 2012 | Translational Research2012，，1： | 1 |
| 14 | High-performance optical-fiber-nonlinearity-based optical waveform monitoring显示文摘 | WESTLUND M ANDREKSON P A SUNNERUD H | 2005 | J Lightwave Technol2005，23，6： | 1 |
| 15 | Neuroanatomy of the pain system and of the pathways that modulate pain 显示文摘 | Willis WD Westlund K | 1997 | J Clin Neurophysiol1997，14，1： | 1 |
| 16 | Excitatory amino acid receptor involvement in peripher - alnocieiptive transmission in rats 显示文摘 | Lawand NB Willis WD Westlund KN | 1997 | Eur J Pharmaeol1997，324，23： | 1 |
| 17 | Effect of low weekly doses of mifepristone on ovarian function and endometrial development显示文摘 | Gemzell-Danielsson K Westlund P Johannisson E | 1996 | Hum Reprod1996，11，2： | 1 |
| 18 | Dysregulated TNFα promotes cytokine proteome profile increases and bilateral orofacial hypersensitivity显示文摘 | F. Ma L. Zhang H.S. Oz M. Mashni K.N. Westlund | 2015 | Neuroscience2015，，： | 1 |
| 19 | Robustness of Partial Least-Squares Method for Estimating Latent Variable Quality Structures 显示文摘 | Cassel C Hackl P Westlund A H | 1999 | Journal of Applied Statistics1999，26，4： | 1 |
| 20 | Effect of low weekly does of mifepritone on ovarian function and endmetrial development显示文摘 | Gemzell-Danielsson K Westlund P | 1996 | Hum Reprod1996，11，2： | 1 |
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