The Intestinal Microvasculature as a Therapeutic Target in Inflammatory Bowel Disease
ABSTRACT Chronic inflammation is a complex biologic process which involves immune as well as non-immune cells including the microvasculature and its endothelial lining. Growing evidence suggests that the microvasculature plays an integral role in the pathophysiology of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis). The microvasculature contributes to chronic inflammation through altered leukocyte recruitment, impaired perfusion, and angiogenesis leading to tissue remodeling. These diverse areas of IBD microvascular biology represent therapeutic targets that are currently undergoing investigation.
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- "The microcirculation and its lining endothelium play a central role in the initiation and perpetuation of the inflammatory response, as well as in tissue remodelling during chronic inflammation. Investigation into the cellular and molecular mechanisms in human inflammatory bowel disease , such as ulcerative colitis, has demonstrated a central role for the intestinal microvascular endothelium in both normal mucosal immunity and the dysregulated chronic inflammation that characterizes IBD . There is now increasing evidence to suggest that neovascularization in response to tissue damage may involve bone marrow-derived endothelial progenitor cells . "
ABSTRACT: Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease, characterized by alternating stages of clinically active and inactive disease. UC exhibits several inflammatory characteristics, including immune activation, leukocyte infiltration, and altered vascular density. In UC, many of the upregulated inflammatory cytokines are proangiogenic and are released by diverse cell populations, such as infiltrating immune cells and endothelial cells (EC). Increasing evidences suggest that neovascularisation may involve also endothelial progenitor cells (EPCs). In this study we evaluated EPCs recruitment and homing, assessed by CXCR4 expression, in both acute and remitting phase of UC. We report an overall decrease of EPCs in UC patients (controls = 97,94 ± 37,34 cells/mL; acute = 31,10 ± 25,38 cells/mL; remitting = 30,33 ± 19,02 cells/mL; for both UC groups versus controls). Moreover CXCR4+-EPCs, committed to home in inflammatory conditions, were found to be reduced in acute UC patients compared to both remitting patients and controls (acute = 3,13 ± 4,61 cells/mL; controls = 20,12 ± 14,0; remitting = 19,47 ± 12,83; ). Interestingly, we found that administration of anti-inflammatory drugs in acute UC is associated with an increase in circulating EPCs, suggesting that this therapy may exert a strong influence on the progenitor cells response to inflammatory processes.Gastroenterology Research and Practice 02/2015; 2015:1-6. DOI:10.1155/2015/843980 · 1.75 Impact Factor
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ABSTRACT: A CAPP/PPC scheduling integration model is proposed based on the decentralized decision-making architecture of the Mediator in this paper and it can be used to solve the problem of the dynamic scheduling in practical production. Mediator technology and contract net are effectively combined in this model so that mediator can be used to carry out management and control in process plan and production scheduling integration model and contract net can be used as the bidding tool in dynamic scheduling, while the equipment and the course of concrete processing in production is completed by Agent technology, whereby the task sequence and optimization, bidding process and system evaluation can be realized. The dynamic scheduling can be accomplished under the mechanism of negotiation and coordination, whereby simplifying the reasoning mechanism of Agent and reducing the information lots in communication. The scheduling simulation for a randomly achieved emergent task illustrates that the method is very effective for the dynamic scheduling and rescheduling in production system with the frequently-changed environment.Machine Learning and Cybernetics, 2005. Proceedings of 2005 International Conference on; 09/2005