Development of in vivo biotransformation enzyme assays for ecotoxicity screening: In vivo measurement of phases I and II enzyme activities in freshwater planarians

2016 ◽  
Vol 130 ◽  
pp. 19-28 ◽  
Author(s):  
Mei-Hui Li
2020 ◽  
Vol 21 (13) ◽  
pp. 4708
Author(s):  
Hannu Raunio ◽  
Olli Pentikäinen ◽  
Risto O. Juvonen

in vivo methods, such as spectrophotometric, fluorometric, mass spectrometric,and radioactivity-based techniques. In fluorescence-based assays, the reaction produces a fluorescentproduct from a nonfluorescent substrate or vice versa. Fluorescence-based enzyme assays areusually highly sensitive and specific, allowing measurements on small specimens of tissues withlow enzyme activities. Fluorescence assays are also amenable to miniaturization of the reactionmixtures and can thus be done in high throughput. 7-Hydroxycoumarin and its derivatives arewidely used as fluorophores due to their desirable photophysical properties. They possess a large -conjugated system with electron-rich and charge transfer properties. This conjugated structure leadsto applications of 7-hydroxycoumarins as fluorescent sensors for biological activities. We describe inthis review historical highlights and current use of coumarins and their derivatives in evaluatingactivities of the major types of xenobiotic-metabolizing enzyme systems. Traditionally, coumarinsubstrates have been used to measure oxidative activities of cytochrome P450 (CYP) enzymes. For thispurpose, profluorescent coumarins are very sensitive, but generally lack selectivity for individual CYPforms. With the aid of molecular modeling, we have recently described several new coumarin-basedsubstrates for measuring activities of CYP and conjugating enzymes with improved selectivity.


Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Margit Biehl ◽  
Philipp Damm ◽  
Adam Trepczynski ◽  
Stefan Preiss ◽  
Gian Max Salzmann

Abstract Purpose Despite practised for decades, the planning of osteotomy around the knee, commonly using the Mikulicz-Line, is only empirically based, clinical outcome inconsistent and the target angle still controversial. A better target than the angle of frontal-plane static leg alignment might be the external frontal-plane lever arm (EFL) of the knee adduction moment. Hypothetically assessable from frontal-plane-radiograph skeleton dimensions, it might depend on the leg-alignment angle, the hip-centre-to-hip-centre distance, the femur- and tibia-length. Methods The target EFL to achieve a medial compartment force ratio of 50% during level-walking was identified by relating in-vivo-measurement data of knee-internal loads from nine subjects with instrumented prostheses to the same subjects’ EFLs computed from frontal-plane skeleton dimensions. Adduction moments derived from these calculated EFLs were compared to the subjects’ adduction moments measured during gait analysis. Results Highly significant relationships (0.88 ≤ R2 ≤ 0.90) were found for both the peak adduction moment measured during gait analysis and the medial compartment force ratio measured in vivo to EFL calculated from frontal-plane skeleton dimensions. Both correlations exceed the respective correlations with the leg alignment angle, EFL even predicts the adduction moment’s first peak. The guideline EFL for planning osteotomy was identified to 0.349 times the epicondyle distance, hence deducing formulas for individualized target angles and Mikulicz-Line positions based on full-leg radiograph skeleton dimensions. Applied to realistic skeleton geometries, widespread results explain the inconsistency regarding correction recommendations, whereas results for average geometries exactly meet the most-consented “Fujisawa-Point”. Conclusion Osteotomy outcome might be improved by planning re-alignment based on the provided formulas exploiting full-leg-radiograph skeleton dimensions.


2006 ◽  
Vol 142 (6) ◽  
pp. 748-750 ◽  
Author(s):  
V. A. Mamisashvili ◽  
N. T. Mchedlishvili ◽  
E. T. Chachanidze ◽  
K. N. Urotadze ◽  
M. V. Gongadze

2021 ◽  
pp. 135245852110017
Author(s):  
Lisa Eunyoung Lee ◽  
Irene M Vavasour ◽  
Adam Dvorak ◽  
Hanwen Liu ◽  
Shawna Abel ◽  
...  

Background: Myelin water imaging (MWI) was recently optimized to provide quantitative in vivo measurement of spinal cord myelin, which is critically involved in multiple sclerosis (MS) disability. Objective: To assess cervical cord myelin measurements in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (ProgMS) participants and evaluate the correlation between myelin measures and clinical disability. Methods: We used MWI data from 35 RRMS, 30 ProgMS, and 28 healthy control (HC) participants collected at cord level C2/C3 on a 3 T magnetic resonance imaging (MRI) scanner. Myelin heterogeneity index (MHI), a measurement of myelin variability, was calculated for whole cervical cord, global white matter, dorsal column, lateral and ventral funiculi. Correlations were assessed between MHI and Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9HPT), timed 25-foot walk, and disease duration. Results: In various regions of the cervical cord, ProgMS MHI was higher compared to HC (between 9.5% and 31%, p ⩽ 0.04) and RRMS (between 13% and 26%, p ⩽ 0.02), and ProgMS MHI was associated with EDSS ( r = 0.42–0.52) and 9HPT ( r = 0.45–0.52). Conclusion: Myelin abnormalities within clinically eloquent areas are related to clinical disability. MWI metrics have a potential role for monitoring subclinical disease progression and adjudicating treatment efficacy for new therapies targeting ProgMS.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Brett H. Hokr ◽  
Joel N. Bixler

AbstractDynamic, in vivo measurement of the optical properties of biological tissues is still an elusive and critically important problem. Here we develop a technique for inverting a Monte Carlo simulation to extract tissue optical properties from the statistical moments of the spatio-temporal response of the tissue by training a 5-layer fully connected neural network. We demonstrate the accuracy of the method across a very wide parameter space on a single homogeneous layer tissue model and demonstrate that the method is insensitive to parameter selection of the neural network model itself. Finally, we propose an experimental setup capable of measuring the required information in real time in an in vivo environment and demonstrate proof-of-concept level experimental results.


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