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| 1 | 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 |
| 2 | Expanding geriatrics into subspeciahy internal medicine healthcare, research and education :caring for older adults and the T显示文摘 | High K P Clayton C P Woolard N | 2002 | Am J Med2002，113，6： | 1 |
| 3 | Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society显示文摘 | Satter E N High W A | 2008 | Pediatr Dermatol2008，，： | 1 |
| 4 | 显示文摘 | Hu X Dong H Y Qiu Z N et aL The effect of high magnetic field characterized by kinetics:Enhancing the biodegradation of acid red 1 with a strain of Bacillus sp | 2007 | International Biodeteriomtion & Biodegradation2007，60，4： | 1 |
| 5 | Two types of 1-D п-conjugated polymers:change transfer and polaronic ferromagnets 显示文摘 | Tyutyulkov N Molecular design of high spin polymers with ferromagnetic coupling among the electrons | 1996 | Pure & Appl Chem1996，68，2： | 1 |
| 6 | 4 of the circumsporozoite protein: signilieance for malarial sporozoite attachment to hepato cytes 显示文摘 | Ancsin JB R Kisilevsky A binding site for highly sullated hepa- ran sulfate is identified in the N terminu | 2004 | J BiolChem2004，279，21： | 1 |
| 7 | IpaB of Shigella flexneri causes entry into epithetical cells and escape from the phago cytic vacuole 显示文摘 | High N Mounier J Prevost M C | 1992 | Embo J1992，11，： | 1 |
| 8 | Presentation,histopathologic findings,and clinical outcomes in 7 cases of melanoma in situ of the nail unit显示文摘 | High WA Quirey RA Guillén DR | 2004 | Arch Dermatol2004，140，9： | 1 |
| 9 | Bacterial coaggregation: an integral process in the development of multi-species biofilms 显示文摘 | Riekard A H Gilbert P High N J Kolenbrander P E Handley P S | 2003 | Trends Microbiol2003，11，2： | 1 |
| 10 | Expanding geriatrics into subspecialty internal medicine healthcare,research and education:caring for older adults and the T显示文摘 | High K P Clayton C P Woolard N | 2002 | Am J Med2002，113，6： | 1 |
| 11 | (Indian mustard) line by antisense suppression of the fad2 gene显示文摘 | SIVARAMAN I ARAMUGAM N SODHI YS et aL Development of high oleic and low linoleic acid transgenics in a zero erucic acid Brassica juncea L | 2004 | Molecular Breeding2004，13，4： | 1 |
| 12 | Corn- study and vitamin C loss kinetics in pasteurised processed reconstituted orange juice显示文摘 | POLYDERA parative shelf life and high pressure Food Engineering A C STOFOROS N G TAOUKIS P S | 2003 | Journal of2003，，60： | 1 |
| 13 | 5 events in the eastern Mediterranean显示文摘 | Kocak M Mihalopoulos N Kubilay Contributions of natural sources to high PM10 and PM2 | 2007 | Atmospheric Environment2007，41，18： | 1 |
| 14 | Extensive evaluation of the instrumentation laboratory IL test D- Dimer immunoturbidimetric assay on the ACL 9000 determines the D-Dimer cutoff value for reliable exclusion of venous thromboembolism显示文摘 | Curtin N Highe G Harris M | 2004 | Lab Hematol2004，10，2： | 1 |
| 15 | provenances显示文摘 | MARCAR N E ZOHAR Y GUO J M CRAWFORD D F Effect of NaCl and high pH on seedling growth of 15 Eucalyptus camaldulensis Dehnh | 2002 | New Forests2002，23，： | 1 |
| 16 | Extensive evaluation of the instrumentation laboratory IL test D-Dimer immunoturbidimetric assay on the ACL 9000 determines the D-Dimer cutoff value for reliable exclusion of venous thrombo embolism显示文摘 | Curtin N Highe G Harris M | 2004 | Lab Hematol2004，10，2： | 1 |
| 17 | The role of licA phase variation in the pathogenesis of invasive disease by Haemophilus influenzae type b显示文摘 | HUMPHRIES H E HIGH N J | 2002 | FEMS Immunol Med Microbiol2002，34，3： | 1 |
| 18 | Fast solution of Vandermonde-like systems involving orthogonal polynomials显示文摘 | HIGH AM N J | 1988 | MMAJ Numer Anal1988，8，： | 1 |
| 19 | Modulation of MMP-9 activity by NGAL显示文摘 | Yan L Borregaard N Kjeldsen L : The high molecular weight urinary matrix metaUoproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL) | 2001 | J Biol Chem2001，276，37： | 1 |
| 20 | Determining the methotrexate concentration in serum with the fluorescence polarization Ly (FPIA)-a comparison with the enzyme immunoassay ( EMIT ) 显示文摘 | Y and high 1986 8 Liappis N | 1986 | Klin Padiatr1986，198，1： | 1 |
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