Hepatic encephalopathy An imbalance between aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) has been described; this would lead to the generation of false neurotransmitters (such octopamine and 2-hydroxyphenethylamine). Dysregulation of the serotonin system, too, has been reported. Depletion of zinc and accumulation of manganese may play a role. Inflammation elsewhere in the body may precipitate encephalopathy through the action of cytokines and bacterial lipopolysaccharide on astrocytes. The diagnosis of hepatic encephalopathy can only be made in the presence of confirmed liver disease (types A and C) or a portosystemic shunt (type B), as its
Organ-on-a-chip models that replicate aspects of the human body as closely as possible and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multi-organ metabolic interactions. Multi compartment micro fluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models that represent the mass transfer of compounds in compartmental models of the mammalian body, may contribute to improving the drug development process. Mathematical pharmacokinetic (PK) models aim to estimate concentration-time profiles within each organ on the basis of the initial drug dose. Such mathematical models can be