Abstract: Many enzymes and transporters involved in the hepatic clearance of drugs also play an important role in endogenous compound transport. Inhibition of some of these active mechanisms has frequently been shown to be associated with Drug-Induced Liver Injury (DILI). The Extended Clearance Model (ECM) describes the complex interplay between the different processes driving hepatic clearance, namely sinusoidal uptake and efflux, canalicular secretion and intracellular metabolism. Based on the ECM, we have derived an integral concept (referred as 1/R-value approach) to quantitatively describe the overall inhibition potency of potential drug candidates on active processes involved in the transport and metabolism of endogenous and safety-relevant compounds. For a small training set of in-house compounds with largely complete in vitro inhibition and in vivo exposure data, accurate ECM-based prediction of DILI was realized. Additionally, prediction of several cases of DILI for a comprehensive validation set of external compounds was achieved with no major false-positive results. However, due to general incompleteness of the required input information available in the public space (the most probable reason for the large number of false-negatives in the test set) the overall legitimacy of ECM for large-scale prediction of cell stress mediated DILI still needs to be demonstrated. In order to advance and accelerate science in this exciting but complex field, a more transparent and open sharing of data is therefore urgently needed and should be encouraged.Abstract: Many enzymes and transporters involved in the hepatic clearance of drugs also play an important role in endogenous compound transport. Inhibition of some of these active mechanisms has frequently been shown to be associated with Drug-Induced Liver Injury (DILI). The Extended Clearance Model (ECM) describes the complex interplay between the differen...Show More
Abstract: Protein is one of the main nutrients that will be in short supply in the future. Alternative protein sources and production methods are required to fulfil the demand of protein requirements. Proteins from microalgae represent potential raw materials for the generation of protein based food ingredients. Arthospira platensis harbors high protein concentrations and one of the most important factors influencing successful extraction of protein is accessibility of the protein molecules. Process optimization and statistical analysis is necessary to maximize protein extraction. This study attempts to evaluate and compare various methods for their reliability in extracting microalgal proteins. Five different extraction methods namely alkali, enzymatic, thermal, microwave assisted and ultrasonic extraction were performed to obtain protein from A. platensis. Functional properties of the protein isolates were determined at various pH levels. Highest protein yield of 84% was obtained in ultrasound extraction. The lowest solubility of protein was found at pH 5.0 (0.27%) and highest solubility of protein was obtained at pH 9.0 (74.90%). Water holding capacity of protein isolates of S. platensis was in the range of 0.902 – 1.341 gwater/gprotein. The foaming capacity ranged from 19.37 to 41.28%, with the lowest and maximum values obtained at pH 5.0 and 3.0, respectively. Maximum value of foam stability at pH 5.0 was 31.24% and this subsequently decreased when the pH increased. The results revealed that both microwave assisted and ultrasound extraction methods were found suitable to make bioavailability of algal proteins from Arthospira platensis.Abstract: Protein is one of the main nutrients that will be in short supply in the future. Alternative protein sources and production methods are required to fulfil the demand of protein requirements. Proteins from microalgae represent potential raw materials for the generation of protein based food ingredients. Arthospira platensis harbors high protein conc...Show More
