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The GIOME:Concept and current role in gastrointestinal tract studies

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World Journal of Gastroenterology 2007年第9期13卷 1333-1334页

作者： gregersen, hans

The goal of the Physiome Project is to understand and describe the physiology and pathophysiology of the human organism. Multiscale mathematical and computer models are developed within this concept to help understand human health. From its beginning about 15 years ago, most of the focus has been in the cardiac field (the Cardiome project) but other areas are developing as well now.

关键词： Gastroenterology

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

Viscosity of food boluses affects the axial force in the esophagus

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World Journal of Gastroenterology 2011年第15期17卷 1982-1988页

作者： Flemming Gravesen Niall Behan Asbjorn Drewes hans gregersen Mech-Sense Aalborg Hospital Hobrovej 9000 Aalborg Denmark Vysera Biomedical Ltd. BMR House Parkmore Business Park West Galway Ireland Sino-Danish Center for Education and Research Niels Jensens Vej 28000 Aarhus Denmark

AIM: To study the effect of viscosity on axial force in the esophagus during primary peristalsis using a newly validated impedance-based axial force recording technique. METHODS: A probe able to simultaneously measure both axial force and manometry was positioned above the lower esophageal sphincter. Potable tap water and three thickened fluids were used to create boluses of different viscosities. Water has a viscosity of 1 mPa·s. The three thickened fluids were made with different concentrations of Clinutren Instant thickener. The viscous fluids were in appearance comparable to pudding (2 kPa·s), yogurt (6 kPa·s) and slush ice (10 kPa·s). Six healthy volunteers swallowed 5 and 10 mL of boluses multiple times. RESULTS: The pressure amplitude did not increase with the bolus viscosity nor with the bolus volume whereas the axial force increased marginally with bolus volume (0.1 > P > 0.05). Both techniques showed that contraction duration increased with bolus viscosity (P < 0.01). Association was found between axial force and pressure but the association became weaker withincreasing viscosity. The pressure amplitude did not increase with the viscosity or bolus volume whereas the axial force increased marginally with the bolus size. CONCLUSION: This indicates a discrepancy between the physiological functions that can be recorded with axial force measurements and pressure measurements.

关键词： Axial force Manometry Esophagus Primary peristalsis Viscosity

New technologies in gastrointestinal research

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World Journal of Gastroenterology 2009年第2期15卷 129-130页

作者： Asbjφrn Mohr Drewes hans gregersen Mech-Sense Department of Gastroenterology Aalborg University Hospital DK-9000 Aalborg Denmark

This issue presents different new techniques aiming to increase our understanding of the gastrointestinal system and to improve treatment. The technologies cover selected methods to evoke and assess gut pain, new methods for imaging and physiological measurements, histochemistry, pharmacological modelling etc. There is no doubt that the methods will revolutionize the diagnostic approach in near future.

关键词： Pain Gut Brain Sphincter Imaging Drug

Morphological properties and residual strain along the small intestine in rats

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World Journal of Gastroenterology 2002年第2期8卷 312-317页

作者： hans gregersen Biomechanics Lab Centre for Sensory-Motor InteractionAalborg University and Department of surgery AAalborg HospitalDenmark

AIM: Residual stress and strain are important for gastrointestinal function and relate to the geometric configuration, the loading conditions and the zero-stress state of the gastrointestinal tract. The purpose of this project is to provide morphometric data and residual strains for the rat small intestine ( n =11). METHODS: To approach the no-load state, the intestine was surgically excised, transferred to an organ bath and cut transversely into short ring-shaped segments. Each ring was cut radially for obtaining the zero-stress state. The residual stress can be characterised by an opening angle. The strain difference between the zero-stress state and the no-load state is called residual strain. RESULTS: Large morphometric variations were found along the small intestine. The wall thickness was highest in the proximal duodenum and decreased in distal direction along the axis of the small intestine (P<0.001). The circumferential length of the inner and outer surfaces decreased rapidly along the length of duodenum by 30-50% (P<0.001). The wall area and lumen area showed a similar pattern (P<0.001). In zero-stress state the rings always opened up after making the cut. The experiments resulted in larger inner circumferential length and smaller outer circumferential length when compared to the no-load state. The wall thickness and wall area did not differ between the no-load and zero-stress state. The opening angle and tangent rotation angle increased along the length of the duodenum and had its highest value 30% down the intestine. Further down the intestine it decreased again (P<0.001). The serosal residual strain was tensile with the highest value close to the ligament of Treitz (P<0.001). The mucosal residual strain was compressive in all segments of the small intestine with average values between -0.25 and -0.4 and with the lowest values close to the ligament of Treitz (P<0.001). CONCLUSION: Axial variation in morphometric properties and residual s

关键词： Animals In Vitro Intestine, Small histology Male Rats Rats, Sprague-Dawley Research Support, Non-U.S. Gov't Stress, Mechanical

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

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World Journal of Gastroenterology 2006年第18期12卷 2805-2817页

作者： Asbjφrn Mohr Drewes Lars Arendt-Nielsen Peter Funch-Jensen hans gregersen Center for Visceral Biomechanics and Pain Department of GastroenterologyAalborg Hospitaland Center for Sensory-Motor InteractionsDepartment of Health Science and TechnologyAalborg UniversityDenmark Department of Surgical Gastroenterology L Aarhus HospitalDenmark

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

关键词： Pain Gut Experimental Chest pain Esophagitis

Gastrointestinal tract modelling in health and disease

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World Journal of Gastroenterology 2009年第2期15卷 169-176页

作者： Dong-Hua Liao Jing-Bo Zhao hans gregersen hans gregersen Mech-Sense Aalborg Hospital DK-9100 Aalborg Denmark Institute of Health Technology Aalborg University Denmark Haukeland University Hospital Bergen Norway

The gastrointestinal (GI) tract is the system of organs within multi-cellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. The various patterns of GI tract function are generated by the integrated behaviour of multiple tissues and cell types. A thorough study of the GI tract requires understanding of the interactions between cells, tissues and gastrointestinal organs in health and disease. This depends on knowledge, not only of numerous cellular ionic current mechanisms and signal transduction pathways, but also of large scale GI tissue structures and the special distribution of the nervous network. A unique way of coping with this explosion in complexity is mathematical and computational modelling; providing a computational framework for the multilevel modelling and simulation of the human gastrointestinal anatomy and physiology. The aim of this review is to describe the current status of biomechanical modelling work of the GI tract in humans and animals, which can be further used to integrate the physiological, anatomical and medical knowledge of the GI system. Such modelling will aid research and ensure that medical professionals benefit, through the provision of relevant and precise information about the patient's condition and GI remodelling in animal disease models. It will also improve the accuracy and efficiency of medical procedures, which could result in reduced cost for diagnosis and treatment.

关键词： Gastrointestinal tract Computational modelling Biomechanics Remodelling Disease

Proximal and distal esophageal sensitivity is decreased in patients with Barrett’s esophagus

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World Journal of Gastroenterology 2011年第4期17卷 514-521页

作者： Anne L Kraru Sφren S Olesen Peter Funch-Jensen hans gregersen Asbjφrn M Drewes Mech-Sense Department of Gastroenterology Aalborg Hospital Aarhus University Hospital Department of Surgery L Aarhus University Hospital

AIM: To investigate sensations to multimodal pain stimulation in the metaplastic and normal parts of the esophagus in patients with Barrett’s esophagus (BE). METHODS: Fifteen patients with BE and 15 age-matched healthy volunteers were subjected to mechanical, thermal and electrical pain stimuli of the esophagus. Both the metaplastic part and the normal part (4 and 14 cm, respectively, above the esophago-gastric junction) were examined. At sensory thresholds the stimulation intensity, referred pain areas, and evoked brain potentials were recorded. RESULTS: Patients were hyposensitive to heat stimulation both in the metaplastic part [median stimulation time to reach the pain detection threshold: 15 (12-34) s vs 14 (6-23) s in controls; F = 4.5, P = 0.04] and the normal part of the esophagus [median 17 (6-32) s vs 13 (8-20) s in controls; F = 6.2, P = 0.02]. Furthermore, patients were hyposensitive in the metaplastic part of the esophagus to mechanical distension [median volume at moderate pain: 50 (20-50) mL vs 33 (13-50) mL in controls; F = 5.7, P = 0.02]. No indication of central nervous system abnormalities was present, as responses were comparable between groups to electrical pain stimuli in the metaplastic part [median current evoking moderate pain: 13 (6-26) mA vs 12 (9-24) mA in controls; F = 0.1, P = 0.7], and in the normal part of the esophagus [median current evoking moderate pain: 9 (6-16) mA, vs 11 (5-11) mA in controls; F = 3.4, P = 0.07]. Furthermore, no differences were seen for the referred pain areas (P-values all > 0.3) or latencies and amplitudes for the evoked brain potentials (P-values all > 0.1). CONCLUSION: Patients with BE are hyposensitive both in the metaplastic and normal part of esophagus likely as a result of abnormalities affecting peripheral nerve pathways.

关键词： Barrett’s esophagus Heat Multimodal Pain Sensitivity

High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis

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Regenerative Biomaterials 2016年第4期3卷 257-267页

作者： Yi Wang Juhui Qiu Shisui Luo Xiang Xie Yiming Zheng Kang Zhang Zhiyi Ye Wanqian Liu hans gregersen GuixueWang Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing400030China Taiji Group Co LtdChongqing401147China

Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic *** of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular *** stress(SS)influences the formation and development of *** current review focuses on the vulnerable plaques observed in the high shear stress(HSS)regions,which localizes at the proximal region of the plaque intruding into the *** vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque *** results greatly challenge the established belief that low shear stress is important for expansive remodelling,which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions.

关键词： high shear stress angiogenesis outward remodelling vulnerable plaque vascular smooth muscle cells