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Journal of Pharmacy and Pharmacology 2014年第4期2卷 231-242页

作者： Hans Gregersen Asbjorn Mohr Drewes giome Center College of Bioengineering Chongqing University Chongqing 400030 China giome institute GIOME Free Zone Enterprise Ras AI Khaimah 10055 United Arab Emirates Department of Gastroenterology Aalborg University Hospital Aalborg DK 9000 Denmark

Characterizations of pain and other sensory symptoms are very important for diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have developed into a new area for multimodal assessment with electrical, mechanical, thermal and chemical stimulation of pain pathways in the human gut. Stimulation with this technology mimics to a large degree the pain experienced by patients seeking the health system for treatment. Multimodal methods have increased our understanding of peripheral receptors in the gut in health and disease. Combined with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases such as systemic sclerosis and diabetes. Multimodal technology can also be used to unravel central pain mechanisms involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often found in patients with chronic gut pain. Hence methods relying on multimodal pain stimulation may help to understand symptoms in these patients. In addition, multimodal methods have been used to gain more insight into the drug effects against pain. It is expected that multimodal methods represent a maj or step forward in the future characterization and treatment of patients with various gastrointestinal diseases.

关键词： Pain cut experimental allodynia hyperalgesia neurophysiology

Relationships of CDXs and apical sodium-dependent bile acid transporter in Barrett's esophagus

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World Journal of Gastroenterology 2013年第18期19卷 2736-2739页

作者： Jingbo Zhao Hans Gregersen Department of Gastroenterology and Surgery Aalborg University Hospital College of Bioengineering Chongqing University the giome institute DK-8000 Aarhus Denmark

Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells. Ectopic expression of CDX1 and CDX2 occurs in BE. The apical sodium-dependent bile acid transporter (ASBT) is expressed primarily in terminal ileum where it is a key factor for intestinal reabsorption of bile salts. In addition to upregulation of CDX1 and CDX2, ASBT expression is up-regulated in BE. Furthermore, both CDX1/CDX2 and ASBT expressions are down-regulated in high-grade esophageal dysplasia. The alteration of the above-mentioned factors calls for attention: what is the relationship between CDXs and ASBT aberrant expression in BE? In this commentary, we discuss this issue on basis of the recent study done by Ma et al .

关键词： Esophagus Intestinal metaplasia Caudal-related homeodomain transcription factors Apical sodiumdependent bile acid transporter Aberrant expression

Changes of phasic and tonic smooth muscle function of jejunum in type 2 diabetic Goto-Kakizaki rats

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World Journal of Diabetes 2013年第6期4卷 339-348页

作者： Jing-Bo Zhao Peng-Min Chen Hans Gregersen Department of Gastroenterology and Surgery Aalborg University HospitalDK 9000 AalborgDenmark The College of Bioengineering Chongqing University Department of Molecular Biology Institute of Clinical MedicineChina-Japan Friendship Hospital the giome institute GIOME FZERas AlKhaimah 6300United Arab Emirates

AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive ***:Seven diabetic Goto-Kakizaki(GK)male rats,32-wk old(GK group),and 9 age-matched normal Wistar rats(Normal group)were included in the *** segments were distended up to a pressure of10 cm H2O in an organ bath containing 37℃Krebs solution with addition of carbachol(CA).The pressure and outer diameter changes were synchronously *** conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and *** phasic,tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state *** active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive ***:Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group(mucosa,755.8±63.3 vs 633.1±59.1μm,P0.05;stress,0.25±0.03 vs 0.35±0.06 kPa,P>0.05).The amplitude of total phasic,total tonic,active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal ***,the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal *** normalized to muscle layer thickness,the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal *** difference was

关键词： Intestine Diabetes Muscle function Stress-strain curves Carbachol Rat

Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

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World Journal of Diabetes 2015年第4期6卷 662-672页

作者： Peng-Min Chen Hans Gregersen Jing-Bo Zhao Department of Molecular Biology Institute of Clinical MedicineChina-Japan Friendship Hospital giome Center College of BioengineeringChongqing University institute of Clinical Medicine Aarhus University

AIM:To investigate changes in advanced glycation end products(AGEs) and their receptor(RAGE) expression in the gastrointestinal(GI) tract in type 2 diabetic ***:Eight inherited type 2 diabetic rats GotoKakizak(GK) and ten age-matched normal rats were used in the *** 18 wk of age,the body weight and blood glucose were measured every week and 2 wk *** the rats reached 32 wk,twocentimeter segments of esophagus,duodenum,jejunum,ileum,and colon were excised and the wet weight was *** segments were fixed in 10% formalin,embedded in paraffin and five micron sections were *** layer thickness was measured in Hematoxylin and Eosin-stained *** [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis ***:The blood glucose concentration(mmol/L) at 18 wk age was highest in the GK group(8.88 ± 1.87 vs 6.90 ± 0.43,P < 0.001),a difference that continued to exist until the end of the *** wet weight per unit length(mg/cm) increased in esophagus,jejunum and colon from the normal to the GK group(60.64 ± 9.96 vs 68.56 ± 11.69,P < 0.05 for esophagus; 87.01 ± 9.35 vs 105.29 ± 15.45,P < 0.01 for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90,P < 0.05 for colon).Histologically,the layer thickness of the GItract was higher for esophagus,jejunum and colon in the GK group [full thickness(μm):575.37 ± 69.22 vs 753.20 ± 150.41,P < 0.01 for esophagus; 813.51 ± 44.44 vs 884.81 ± 45.31,P < 0.05 for jejunum; 467.12 ± 65.92 vs 572.26 ± 93.60,P < 0.05 for colon].In esophagus,the AGE and RAGE mainly distributed in striated muscle cells and squamous epithelial *** AGE distribution was much stronger in the GK group compared to the normal group both in the striated muscle layer and mucosa layer(immuno-positive area/ total measuring area %:4.52 ± 0.89 vs 10.96 ± 1.34,P < 0.01 for muscle; 8.90 ± 2.62 vs

关键词： Diabetes mellitus Gastrointestinal complications Advanced glycation end products Receptor ofadvanced glycation end products