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Start Over Topic liver Publication Year Range Last 50 years Publisher springer us
835 results

1. Transcriptome analysis of fowl adenovirus serotype 4 infection in chickens

Author

Ruiai Chen, Ren Guangcai, Yuanyuan Yan, Fan Liu, Han Wang, and Miaorong Huang

Subjects
Serotype, Hydropericardium–hepatitis syndrome, Adenoviridae Infections, Notch signaling pathway, Peroxisome proliferator-activated receptor, RNA-Seq, Biology, Real-Time Polymerase Chain Reaction, Serogroup, Fowl adenovirus serotype 4, Pathogenesis, Transcriptome, 03 medical and health sciences, Virology, Genetics, Animals, Molecular pathogenesis, Receptor, Molecular Biology, Gene, Poultry Diseases, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Original Paper, 030306 microbiology, Sequence Analysis, RNA, Aviadenovirus, Gene Expression Profiling, General Medicine, chemistry, Liver, Host-Pathogen Interactions, Differentially expressed genes, RNA-seq, Chickens
Abstract

Fowl adenovirus serotype 4 (FAdV-4) is a causative agent of inclusion body hepatitis and hydropericardium–hepatitis syndrome. These diseases cause considerable economic losses in the global poultry industry and are significant stressors for infected chickens. However, the molecular mechanisms of FAdV-4 pathogenesis are poorly understood. In the present study, we identified differentially expressed genes from the livers of FAdV-4-infected chickens using RNA-seq at 7, 14 and 21 days after FAdV-4 infection. We identified 2395 differentially expressed genes at the three time points. These genes were enriched in variety of biological processes and pathways including PPAR and Notch signaling, cytokine–cytokine receptor interactions and Toll-like receptor signaling pathways. The transcriptional data were validated by quantitative real-time PCR. Our results will assist in the understanding of the molecular pathogenesis of FAdV-4 infection and for developing novel antiviral therapies. Electronic supplementary material The online version of this article (10.1007/s11262-019-01676-w) contains supplementary material, which is available to authorized users.

Published
2019

2. Can Population Modelling Principles be Used to Identify Key PBPK Parameters for Paediatric Clearance Predictions? An Innovative Application of Optimal Design Theory

Author

Dick Tibboel, Amin Rostami-Hodjegan, Elke H. J. Krekels, Elisa A. M. Calvier, Catherijne A. J. Knibbe, Thu Thuy Nguyen, Trevor N. Johnson, and Pediatric Surgery

Subjects
Optimal design, Mathematical optimization, Physiologically based pharmacokinetic modelling, population modelling, Computer science, Metabolic Clearance Rate, Population, Pharmaceutical Science, 030226 pharmacology & pharmacy, Models, Biological, paediatrics, 03 medical and health sciences, 0302 clinical medicine, population optimal design, Stochastic simulation, Drug Discovery, Humans, Pharmacology (medical), Computer Simulation, Tissue Distribution, education, Child, Pharmacology, education.field_of_study, Clinical Trials as Topic, Clinical study design, Organic Chemistry, Whole liver, Uncertainty, 3. Good health, Kinetics, Liver, 030220 oncology & carcinogenesis, Key (cryptography), Molecular Medicine, Identifiability, physiologically-based pharmacokinetic, Biotechnology, Research Paper
Abstract

Purpose Physiologically-based pharmacokinetic (PBPK) models are essential in drug development, but require parameters that are not always obtainable. We developed a methodology to investigate the feasibility and requirements for precise and accurate estimation of PBPK parameters using population modelling of clinical data and illustrate this for two key PBPK parameters for hepatic metabolic clearance, namely whole liver unbound intrinsic clearance (CLint,u,WL) and hepatic blood flow (Qh) in children. Methods First, structural identifiability was enabled through re-parametrization and the definition of essential trial design components. Subsequently, requirements for the trial components to yield precise estimation of the PBPK parameters and their inter-individual variability were established using a novel application of population optimal design theory. Finally, the performance of the proposed trial design was assessed using stochastic simulation and estimation. Results Precise estimation of CLint,u,WL and Qh and their inter-individual variability was found to require a trial with two drugs, of which one has an extraction ratio (ER) ≤ 0.27 and the other has an ER ≥ 0.93. The proposed clinical trial design was found to lead to precise and accurate parameter estimates and was robust to parameter uncertainty. Conclusion The proposed framework can be applied to other PBPK parameters and facilitate the development of PBPK models. Electronic supplementary material The online version of this article (10.1007/s11095-018-2487-1) contains supplementary material, which is available to authorized users.

Published
2018
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49. A microfluidic device mimicking acinar concentration gradients across the liver acinus.

Author

Shih MC, Tseng SH, Weng YS, Chu IM, and Liu CH

Subjects
Aspartate Aminotransferases blood, Cell Line, Dimethylpolysiloxanes chemistry, Equipment Design, Humans, Perfusion, Pressure, Shear Strength, Stress, Mechanical, Surface Properties, Liver cytology, Microfluidic Analytical Techniques instrumentation, Microfluidic Analytical Techniques methods
Abstract

The acinus-mimicking microfluidic chip, which simulates the in vivo condition of the liver, was developed and reported in this paper. The gradient microenvironment of the liver acinus is replicated within this proposed microfluidic chip. The advantage of this acinus-mimicking chip is capable of adjusting the concentration gradient in a relatively short period of time at around 10 s. At the same instance the non-linear concentration gradient can be presented in the various zones within this microfluidic chip. The other advantage of this proposed design is in the convenience of allowing the direct injection of the cells into the chip. The environment within the chip is multi-welled and gel-free with high cell density. The multi-row pillar microstructure located at the entrance of the top and bottom flow channels is designed to be able to balance the pressure of the perfusion medium. Through this mechanism the shear stress experienced by the cultured cells can be minimized to reduce the potential damage flow from the perfusion process. The fluorescence staining and the observations of the cell morphology verify the life and death of the cells. The shear stress experienced by the cells in the various zones within the chip can be effectively mapped. The serum glutamic oxaloacetic transaminase (SGOT) collected from the supernatants was used to determine the effects of the degassing process and the shear stress of the medium flow on the cultured cells.

Published
2013
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