Experimental Validation of Mass Balance Models for in Vitro Cell-Based Bioassays

2019 ◽  
Vol 54 (2) ◽  
pp. 1120-1127 ◽  
Author(s):  
Luise Henneberger ◽  
Marie Mühlenbrink ◽  
Daniel J. Heinrich ◽  
Alexandre Teixeira ◽  
Beate Nicol ◽  
...  
Keyword(s):  
Mass Balance ◽  
Experimental Validation ◽  
Mass Balance Models

scholarly journals Mass Balance, Metabolite Profile, andIn Vitro-In VivoComparison of Clearance Pathways of Deleobuvir, a Hepatitis C Virus Polymerase Inhibitor

2014 ◽  
Vol 59 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Lin-Zhi Chen ◽  
John P. Sabo ◽  
Elsy Philip ◽  
Lois Rowland ◽  
Yan Mao ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Mass Balance ◽  
Metabolite Profile ◽  
Fecal Samples ◽  
Acyl Glucuronide ◽  
Polymerase Inhibitor ◽  
Main Components

ABSTRACTThe pharmacokinetics, mass balance, and metabolism of deleobuvir, a hepatitis C virus (HCV) polymerase inhibitor, were assessed in healthy subjects following a single oral dose of 800 mg of [14C]deleobuvir (100 μCi). The overall recovery of radioactivity was 95.2%, with 95.1% recovered from feces. Deleobuvir had moderate to high clearance, and the half-life of deleobuvir and radioactivity in plasma were ∼3 h, indicating that there were no metabolites with half-lives significantly longer than that of the parent. The most frequently reported adverse events (in 6 of 12 subjects) were gastrointestinal disorders. Two major metabolites of deleobuvir were identified in plasma: an acyl glucuronide and an alkene reduction metabolite formed in the gastrointestinal (GI) tract by gut bacteria (CD 6168), representing ∼20% and 15% of the total drug-related material, respectively. Deleobuvir and CD 6168 were the main components in the fecal samples, each representing ∼30 to 35% of the dose. The majority of the remaining radioactivity found in the fecal samples (∼21% of the dose) was accounted for by three metabolites in which deleobuvir underwent both alkene reduction and monohydroxylation. In fresh human hepatocytes that form biliary canaliculi in sandwich cultures, the biliary excretion for these excretory metabolites was markedly higher than that for deleobuvir and CD 6168, implying that rapid biliary elimination upon hepatic formation may underlie the absence of these metabolites in circulation. The lowin vitroclearance was not predictive of the observedin vivoclearance, likely because major deleobuvir biotransformation occurred by non-CYP450-mediated enzymes that are not well represented in hepatocyte-basedin vitromodels.

Comparison between energy balance and mass balance models for actual evapotranspiration assessment

2009 ◽  
Author(s):  
A. Gentile ◽  
L. Pierce ◽  
G. Ciraolo ◽  
G. Zhang ◽  
G. La Loggia ◽  
...  
Keyword(s):  
Energy Balance ◽  
Mass Balance ◽  
Actual Evapotranspiration ◽  
Mass Balance Models

Investigating Fast- and Slow-settling Phosphorus Fractions in Lakes using Steady-state Modeling

2021 ◽  
Author(s):  
Hamed Khorasani ◽  
Zhenduo Zhu
Keyword(s):  
Steady State ◽  
Mass Balance ◽  
Large Scale ◽  
Hydraulic Residence Time ◽  
Simple Method ◽  
Retention Models ◽  
Mass Balance Models ◽  
Limiting Nutrient ◽  
Fast Settling ◽  
P Retention

<p>Phosphorus (P) is the key and limiting nutrient in the eutrophication of freshwater resources. Modeling P retention in lakes using steady-state mass balance models (i.e. Vollenweider-type models) provides insights into the lake P management and a simple method for large-scale assessments of P in lakes. One of the basic problems in the mass balance modeling of P in lakes is the removal of P from the lake water column by settling. A fraction of the incoming P into the lake from the watershed is associated with fast-settling particles (e.g. sediment particles) that result in the removal of that fraction of P quickly at the lake entrance. However, existing models considering a constant fraction of fast-settling TP for all lakes are shown to result in overestimation of the retention of P in lakes with short hydraulic residence time. In this study, we combine a hypothesis of the fast- and slow-settling P fractions into the steady-state mass balance models of P retention in lakes. We use a large database of lakes to calibrate the model and evaluate the hypothesis. The results of this work can be used for the improvement of the prediction power of P retention models in lakes and help to better understand the processes of P cycling in lakes.</p>

scholarly journals Identification of the Active Constituents and Significant Pathways of Shen-qi-Yi-zhu Decoction on Antigastric Cancer: A Network Pharmacology Research and Experimental Validation

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shuhong Zeng ◽  
Zhibao Yu ◽  
Xintian Xu ◽  
Yuanjie Liu ◽  
Jiepin Li ◽  
...  
Keyword(s):  
Experimental Validation ◽  
Target Genes ◽  
Cell Model ◽  
Network Pharmacology ◽  
Disease Network ◽  
Systematic Method ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Underlying Mechanisms

Shen-qi-Yi-zhu decoction (SQYZD) is an empirical prescription with antigastric cancer (GC) property created by Xu Jing-fan, a National Chinese Medical Master. However, its underlying mechanisms are still unclear. Based on network pharmacology and experimental verification, this study puts forward a systematic method to clarify the anti-GC mechanism of SQYZD. The active ingredients of SQYZD and their potential targets were acquired from the TCMSP database. The target genes related to GC gathered from GeneCards, DisGeNET, OMIM, TTD, and DrugBank databases were imported to establish protein-protein interaction (PPI) networks in GeneMANIA. Cytoscape was used to establish the drug-ingredients-targets-disease network. The hub target genes collected from the SQYZD and GC were parsed via GO and KEGG analysis. Our findings from network pharmacology were successfully validated using an in vitro HGC27 cell model experiment. In a word, this study proves that the combination of network pharmacology and in vitro experiments is effective in clarifying the potential molecular mechanism of traditional Chinese medicine (TCM).

Impact of the choice of surface mass balance models and their calibration on large-scale glacier change projections

2021 ◽  
Author(s):  
Lilian Schuster ◽  
David Rounce ◽  
Fabien Maussion
Keyword(s):  
Mass Balance ◽  
Large Scale ◽  
Model Complexity ◽  
Model Parameters ◽  
Glacier Change ◽  
Surface Mass Balance ◽  
Ice Dynamics ◽  
Surface Mass ◽  
Mass Balance Models ◽  
Intercomparison Study

<p>A recent large model intercomparison study (GlacierMIP) showed that differences between the glacier models is a dominant source of uncertainty for future glacier change projections, in particular in the first half of the century.  Each glacier model has their own unique set of process representations and climate forcing methodology, which makes it impossible to determine the model components that contribute most to the projection uncertainty. This study aims to improve our understanding of the sources of large scale glacier model uncertainty using the Open Global Glacier Model (OGGM), focussing on the surface mass balance (SMB) in a first step. We calibrate and run a set of interchangeable SMB model parameterizations (e.g. monthly vs. daily, constant vs. variable lapse rates, albedo, snowpack evolution and refreezing) under controlled boundary conditions. Based on ensemble approaches, we explore the influence of (i) the parameter calibration strategy and (ii) SMB model complexity on regional to global glacier change. These uncertainties are then put in relation to a qualitative selection of other model design choices, such as the forcing climate dataset and ice dynamics model parameters. </p>

Computational Techniques Application in Environmental Exposure Assessment

2015 ◽  
pp. 471-505
Author(s):  
Karolina Jagiello ◽  
Tomasz Puzyn
Keyword(s):  
Mass Balance ◽  
Exposure Assessment ◽  
Environmental Exposure ◽  
Chemical Properties ◽  
Computational Techniques ◽  
Structure Property ◽  
Mass Balance Models ◽  
Modelling Methodology ◽  
Environmental Exposure Assessment ◽  
Input Variables

In this chapter, the application of computational techniques in environmental exposure assessment was described. The most important groups of these techniques are Multimedia Mass-balance (MM) modelling and Quantitative Structure-Activity/Structure-Property Relationships (QSAR/QSPR) modelling. Multimedia Mass-balance models have been widely utilized for studying Long-Range Transport Potential (LRTP) and overall persistence (POV) of Persistent Organic Pollutants (POPs), regulated by many national and international acts, including the Stockholm Convention on POPs. Recently, a novel modelling methodology that links QSPR and MM has been implemented. According to this approach, the physical/chemical properties required as the input variables for multimedia modelling can be calculated directly from appropriate QSPR models. QSPR models must be previously developed based on the relationships between the chemical structure and the modelled properties (QSPR).

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