scholarly journals Microphysiological Systems: gold standard approach towards in vitro biomimetics and its potential to drive forward the fisheries sector to the next level

2020 ◽  
Vol 8 (2) ◽  
pp. 1095-1101
Author(s):  
Aishwarya Sharma ◽  
Tarang K Shah
Keyword(s):  
Gold Standard ◽  
Standard Approach ◽  
Microphysiological Systems

scholarly journals Evaluation of Fluorescence- and Mass Spectrometry—Based CYP Inhibition Assays for Use in Drug Discovery

2008 ◽  
Vol 13 (5) ◽  
pp. 343-353 ◽  
Author(s):  
Leslie Bell ◽  
Shari Bickford ◽  
Phong Hung Nguyen ◽  
Jianling Wang ◽  
Timothy He ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Gold Standard ◽  
Low Cost ◽  
Liver Microsomes ◽  
Standard Approach ◽  
New Chemical Entities ◽  
Cyp Inhibition ◽  
Inhibitory Potential ◽  
The Impact

The potential for metabolism-related drug-drug interactions by new chemical entities is assessed by monitoring the impact of these compounds on cytochrome P450 (CYP) activity using well-characterized CYP substrates. The conventional gold standard approach for in vitro evaluation of CYP inhibitory potential uses pooled human liver microsomes (HLM) in conjunction with prototypical drug substrates, often quantified by LC-MS/MS. However, fluorescent CYP inhibition assays, which use recombinantly expressed CYPs and fluorogenic probe substrates, have been employed in early drug discovery to provide low-cost, high-throughput assessment of new chemical entities. Despite its greatly enhanced throughput, this approach has been met with mixed success in predicting the data obtained with the conventional gold standard approach (HLM+LC-MS). The authors find that the predictivity of fluorogenic assays for the major CYP isoforms 3A4 and 2D6 may depend on the quality of the test compounds. Although the structurally more optimized marketed drugs yielded acceptable correlations between the fluorogenic and HLM+LC-MS/MS assays for CYPs 3A4, 2D6, and 2C9 ( r 2 = 0.5-0.7; p < 0.005), preoptimization, early discovery compounds yielded poorer correlations ( r 2 ≤ 0.2) for 2 of these major isoforms, CYPs 3A4 and 2D6. Potential reasons for the observed differences are discussed. ( Journal of Biomolecular Screening 2008;343-353)

scholarly journals Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

Biosensors ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 110 ◽  
Author(s):  
Erika Ferrari ◽  
Cecilia Palma ◽  
Simone Vesentini ◽  
Paola Occhetta ◽  
Marco Rasponi
Keyword(s):  
Imaging Techniques ◽  
Biological Models ◽  
Electromechanical Properties ◽  
Human Organs ◽  
Tissue Constructs ◽  
Microphysiological Systems ◽  
Metabolic Activities ◽  
On Chip ◽  
Chip Analysis

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

Microphysiological systems: What it takes for community adoption

2021 ◽  
pp. 153537022110088
Author(s):  
Passley Hargrove-Grimes ◽  
Lucie A Low ◽  
Danilo A Tagle
Keyword(s):  
Rare Diseases ◽  
Development Process ◽  
Emerging Technology ◽  
National Institutes Of Health ◽  
Drug Development Process ◽  
Microphysiological Systems ◽  
Pediatric Populations ◽  
Neural Disorders ◽  
Future Path

Microphysiological systems (MPS) are promising in vitro tools which could substantially improve the drug development process, particularly for underserved patient populations such as those with rare diseases, neural disorders, and diseases impacting pediatric populations. Currently, one of the major goals of the National Institutes of Health MPS program, led by the National Center for Advancing Translational Sciences (NCATS), is to demonstrate the utility of this emerging technology and help support the path to community adoption. However, community adoption of MPS technology has been hindered by a variety of factors including biological and technological challenges in device creation, issues with validation and standardization of MPS technology, and potential complications related to commercialization. In this brief Minireview, we offer an NCATS perspective on what current barriers exist to MPS adoption and provide an outlook on the future path to adoption of these in vitro tools.

An Animal Protection Sponsor's View of MEIC

1997 ◽  
Vol 25 (3) ◽  
pp. 343-345
Author(s):  
Ethel Thurston
Keyword(s):  
Gold Standard ◽  
Animal Cell ◽  
Scientific Evidence ◽  
In Vitro Cytotoxicity ◽  
In Vitro Tests ◽  
Blood Concentrations ◽  
Animal Protection ◽  
Animal Tests ◽  
Lethal Blood

The Multicenter Evaluation of In Vitro Cytotoxicity programme is most important to animal protection, since it has validated 64 in vitro tests using advanced human data for 50 chemicals as the “gold standard”. Therefore, it has been able to compare animal cell tests, human cell tests and whole-animal tests fairly with unbiased scientific evidence. Added bonuses have included the identification and development of missing in vitro information (“missing tests”), publication of time-related lethal blood concentrations for all 50 chemicals, and some preliminary plans to resolve the 50,000 untested (or poorly tested) chemicals in the chemical mountain.

scholarly journals Engineering cardiac microphysiological systems to model pathological extracellular matrix remodeling

2018 ◽  
Vol 315 (4) ◽  
pp. H771-H789 ◽  
Author(s):  
Nethika R. Ariyasinghe ◽  
Davi M. Lyra-Leite ◽  
Megan L. McCain
Keyword(s):  
Cardiovascular Disease ◽  
Extracellular Matrix ◽  
Myocardial Function ◽  
Myocardial Cell ◽  
Three Dimensions ◽  
Model Systems ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Microphysiological Systems

Many cardiovascular diseases are associated with pathological remodeling of the extracellular matrix (ECM) in the myocardium. ECM remodeling is a complex, multifactorial process that often contributes to declines in myocardial function and progression toward heart failure. However, the direct effects of the many forms of ECM remodeling on myocardial cell and tissue function remain elusive, in part because conventional model systems used to investigate these relationships lack robust experimental control over the ECM. To address these shortcomings, microphysiological systems are now being developed and implemented to establish direct relationships between distinct features in the ECM and myocardial function with unprecedented control and resolution in vitro. In this review, we will first highlight the most prominent characteristics of ECM remodeling in cardiovascular disease and describe how these features can be mimicked with synthetic and natural biomaterials that offer independent control over multiple ECM-related parameters, such as rigidity and composition. We will then detail innovative microfabrication techniques that enable precise regulation of cellular architecture in two and three dimensions. We will also describe new approaches for quantifying multiple aspects of myocardial function in vitro, such as contractility, action potential propagation, and metabolism. Together, these collective technologies implemented as cardiac microphysiological systems will continue to uncover important relationships between pathological ECM remodeling and myocardial cell and tissue function, leading to new fundamental insights into cardiovascular disease, improved human disease models, and novel therapeutic approaches.

scholarly journals Performance in vitro of apex locators in determining root length in primary molars

2016 ◽  
Vol 64 (3) ◽  
pp. 244-249
Author(s):  
Fernanda Mara Paiva BERTOLI ◽  
Carolina Dea BRUZAMOLIN ◽  
Flares BARATTO FILHO ◽  
Débora Andrade da SILVA ◽  
Flávia Fagundes Sens TOMAZINHO ◽  
...  
Keyword(s):  
Correlation Coefficient ◽  
Digital Radiography ◽  
Root Canal ◽  
Gold Standard ◽  
Root Length ◽  
Root Resorption ◽  
Primary Molars ◽  
Visual Examination ◽  
Length Determination

ABSTRACT Objective: The aim of the study was to evaluate performance of digital radiographic and two electronic apex locators, Propex II and Root ZX in root canal length determination in primary molars. Methods: 25 primary molars were divided into two groups, G1 without root resorption and G2 with root resorption. The exams were performed using all methods by two experienced examiners, with 1-week interval. The gold standard was determined by visual examination. The methods were statistically analyzed regarding the values of reproducibility and correlated with the gold standard by Pearson´s correlation coefficient. Results: The root canal length determination coincided with gold standard in 22.7% for Root ZX, 17.5% for Propex II and 12.5% for digital radiography. Correlation values were higher in G1, the Root ZX presented the highest values. In G2 the digital radiography showed the lowest correlation. In G1, the intra-examiner reproducibility values ranged from 0.925 to 0.523, and interexaminer 0.863 to 0.670. In G2, the values of intra-examiner reproducibility ranges from 0.864 to 0.097, and inter was 0.774 to 0.379. Conclusion: It was concluded that the methods performance varying according to examiner's experience. The Root ZX presented the highest reproducibility and accuracy.

scholarly journals Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies

2017 ◽  
Vol 19 (5) ◽  
pp. 1499-1512 ◽  
Author(s):  
Nikolaos Tsamandouras ◽  
Wen Li Kelly Chen ◽  
Collin D. Edington ◽  
Cynthia L. Stokes ◽  
Linda G. Griffith ◽  
...  
Keyword(s):  
Pharmacokinetic Studies ◽  
Microphysiological Systems

scholarly journals Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Junio Dort ◽  
Zakaria Orfi ◽  
Paul Fabre ◽  
Thomas Molina ◽  
Talita C. Conte ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gold Standard ◽  
Therapeutic Potential ◽  
Preclinical Study ◽  
Myogenic Cells ◽  
Inflammatory Phenotype ◽  
Myogenic Factors ◽  
Myogenic Progenitor Cells

AbstractLack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by dampening the chronic and excessive inflammatory process; however, they also have numerous harmful side effects that hamper their therapeutic potential. Here, we investigated Resolvin-D2 as a new therapeutic alternative having the potential to target multiple key features contributing to the disease progression. Our in vitro findings showed that Resolvin-D2 promotes the switch of macrophages toward their anti-inflammatory phenotype and increases their secretion of pro-myogenic factors. Moreover, Resolvin-D2 directly targets myogenic cells and promotes their differentiation and the expansion of the pool of myogenic progenitor cells leading to increased myogenesis. These effects are ablated when the receptor Gpr18 is knocked-out, knocked-down, or blocked by the pharmacological antagonist O-1918. Using different mouse models of DMD, we showed that Resolvin-D2 targets both inflammation and myogenesis leading to enhanced muscle function compared to glucocorticoids. Overall, this preclinical study has identified a new therapeutic approach that is more potent than the gold-standard treatment for DMD.

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