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10.1177/1535370217703978 http://scihub22266oqcxt.onion/10.1177/1535370217703978 C5661766!5661766 !28409533     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28409533 &cmd=llinks): Failed to open stream: HTTP request failed! 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Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems |pdf=|usr=}}{{28409533 }} gab.com Text Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems JO: Exp Biol Med (Maywood) http://www.kidney.de/pget.php?&tw=1&pmid=28409533 #FOAvip This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, ?1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices. Twit Text FOAVip Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems ????Exp Biol Med (Maywood) http://www.kidney.de/pget.php?&tw=1&pmid=28409533 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28409533 #FOAvip English Wikipedia <ref>{{Cite pmid|28409533 }}</ref> Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems #MMPMID28409533 Lee-Montiel FT ; George SM ; Gough AH ; Sharma AD ; Wu J ; DeBiasio R ; Vernetti LA ; Taylor DL Exp Biol Med (Maywood) 2017[Oct]; 242 (16 ): 1617-1632 PMID28409533 show ga This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, ?1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices. |Acetaminophen/toxicity [MESH] |Cell Line [MESH] |Fatty Liver/pathology [MESH] |Glucose/metabolism [MESH] |Glycolysis/physiology [MESH] |Hepatocytes/*metabolism [MESH] |Humans [MESH] |Interleukin-6/metabolism [MESH] |Lab-On-A-Chip Devices [MESH] |Lipopolysaccharides [MESH] |Liver/*metabolism [MESH] |Macrophages/cytology [MESH] |Microchip Analytical Procedures/*methods [MESH] |Microfluidics/*methods [MESH] |Monocytes/cytology [MESH] |Oxidative Phosphorylation [MESH] |Oxygen Consumption/*physiology [MESH] |Oxygen/*metabolism [MESH] |Tumor Necrosis Factor-alpha/metabolism [MESH]Control of oxygen tension recapitulates zone-specific functions in hum(epmc).pdf DeepDyve Pubget Overpricing