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Seward B. Rutkove - One of the best experts on this subject based on the ideXlab platform.
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modeling and reproducibility of twin concentric electrical impedance Myography
IEEE Transactions on Biomedical Engineering, 2021Co-Authors: Marti Martinez De Morentin Cardoner, Seward B. Rutkove, Janice A Nagy, Hyeuknam Kwon, Hilda Victoria Gutierrez Pulido, Benjamin SanchezAbstract:Objective: Electrical impedance Myography (EIM) is a recent technology to assess muscle health. As of today, the clinical application of EIM has been applied only to evaluate muscle condition using non-invasive surface electrodes in contact with the skin; however, intermediate tissues at the recording site introduce confounding artifacts which reduce the technique's performance as a biomarker of neuromuscular disorders (NMD). Here, we develop and test in humans a new approach using two concentric needles for intramuscular EIM recordings. Methods: First, we study the recording characteristics of dual concentric needle EIM via analytical models and finite element models (FEMs). Next, the validity of the models is verified by performing experiments on saline and agar phantoms. Finally, 8 subjects with various neuromuscular diseases were studied measuring tibialis anterior, biceps, deltoid, adductor pollicis brevis, first dorsal interosseous and flexor carpi radialis muscles. Results: Analytical and FEM simulations are in good agreement with a maximum experimental discrepancy <8% and <9% using gauge needles 26 and 30, respectively. The inter-session reproducibility, as measured by the intraclass correlation coefficients for all muscles studied, was 0.926, which is comparable or exceeds the reproducibility of other well-established electrophysiological tests to assess muscle health. Conclusion: The reproducibility of the technique support future clinical application of needle EIM for assessment of disease status, either as part of standard patient care or as biomarker measure in clinical trials. Significance: Needle EIM has the potential of becoming a valuable diagnostic tool to evaluate NMD in adult population.
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reducing sample size requirements for future als clinical trials with a dedicated electrical impedance Myography system
Amyotrophic Lateral Sclerosis, 2018Co-Authors: Jeremy M Shefner, Seward B. Rutkove, James B Caress, Michael Benatar, William S David, Michael S Cartwright, Eric A Macklin, Jose L BohorquezAbstract:Objective: In this longitudinal multicenter cohort study, we evaluated the potential of a dedicated electrical impedance Myography (EIM) device to assess ALS progression and the system’s basic repr...
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electrical impedance Myography as a biomarker of myostatin inhibition with actriib mfc a study in wild type mice
Future Science OA, 2018Co-Authors: Janice A Nagy, Kush Kapur, Rebecca S Taylor, Benjamin Sanchez, Seward B. RutkoveAbstract:Aim: We sought to determine the sensitivity of electrical impedance Myography (EIM) to myofiber hypertrophy induced by treatment with various doses of ActRIIB-mFc, an inhibitor of myostatin signali...
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electrical impedance Myography detects age related muscle change in mice
PLOS ONE, 2017Co-Authors: David W Arnold, Rebecca S Taylor, Janice A Nagy, Benjamin Sanchez, Seward B. RutkoveAbstract:Loss of muscle mass and strength represents one of the most significant contributors to impaired function in older adults. Convenient and non-invasive biomarkers are needed that can readily identify and track age-related muscle change. Previous data has suggested electrical impedance Myography (EIM) has the potential to serve in this capacity. In this study we investigated how changes in EIM compared with other standard measures of muscle structure and function in aged compared with young mice. A total of 19 male mice aged approximately 25 months and 19 male mice aged 3 months underwent surface multifrequency EIM of the right gastrocnemius muscle using standard methods. Fore and hind limb grip strength, sciatic compound muscle action potential amplitude, and in-situ force of the gastrocnemius were also measured; after sacrifice, gastrocnemius myofiber size was assessed using standard histology. Spearman correlation coefficients were calculated to investigate the association between EIM and muscle characteristics. EIM in aged animals demonstrated significantly lower 50 kHz impedance phase (p<0.001) and reactance (p<0.01) values as well as reduced multifrequency parameters. In contrast, absolute gastrocnemius muscle mass was no different between young and aged mice (p = 0.58) but was reduced in aged mice after normalization to body mass (p<0.001). Median myofiber size in the aged mice was not different from that of young mice (p = 0.72). Aged mice showed reduced muscle function on the basis of normalized fore limb (p<0.001) and normalized hind limb (p<0.001) grip strength, as well as normalized gastrocnemius twitch (p<0.001) and normalized maximal isometric force (p<0.001). Sciatic compound muscle action potential amplitude was reduced in aged mice (p<0.05). EIM parameters showed good correlation with reduced standard physiological and electrophysiological measures of muscle health. Our study suggests that EIM is sensitive to aged-related muscle change and may represent a convenient and valuable method of quantifying loss of muscle health.
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electrical impedance Myography for assessment of duchenne muscular dystrophy
Annals of Neurology, 2017Co-Authors: Seward B. Rutkove, Amy Pasternak, Craig M Zaidman, Kush Kapur, Lavanya Madabusi, Sung Yim, Adam Pacheck, Heather Szelag, Tim Harrington, Basil T DarrasAbstract:Objective: Sensitive, objective and easily applied methods for evaluating disease progression and response to therapy are needed for clinical trials in Duchenne muscular dystrophy (DMD). In this study, we evaluated whether electrical impedance Myography (EIM) could serve this purpose. Methods: In this non-blinded study, 36 boys with DMD and 29 age-similar healthy boys underwent multifrequency EIM measurements for up to 2 years on 6 muscles unilaterally along with functional assessments. A linear mixed-effects model with random intercept and slope terms was used for the analysis of multifrequency EIM values and functional measures. Seven DMD boys were initiated on corticosteroids; these data were analyzed using a piecewise linear mixed-effects model. Results: In boys >7.0 years, a significant difference in the slope of EIM phase-ratio trajectories in the upper extremity was observed by 6 months of -0.074/month, p=0.023, 95% confidence interval (CI)[-0.013,-0.14]); at two years, this difference was -0.048/month, p<0.0001 95%CI[-0.028,-0.068]. In boys ≤7.0 years, differences appeared at 6 months in gastrocnemius (EIM phase-slope -0.83°/kHz-month, p=0.007 95%CI[-0.26,-1.40]). EIM outcomes showed significant differences earlier than functional tests. Initiation of corticosteroids significantly improved the slope of EIM phase-ratio (0.057/month, p=0.00019 95%CI[0.028,0.086]) and EIM phase-slope (0.14°/kHz-month, p=0.013 95%CI[0.028,0.25]), consistent with corticosteroids' known clinical benefit. Interpretation: EIM detects deterioration in muscles of both younger and older boys by 6 months; it also identifies the therapeutic effect of corticosteroid initiation. Since EIM is rapid to apply, painless, and requires minimal operator training, the technique deserves to be further evaluated as a biomarker in DMD clinical therapeutic trials. This article is protected by copyright. All rights reserved.
Basil T Darras - One of the best experts on this subject based on the ideXlab platform.
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electrical impedance Myography for assessment of duchenne muscular dystrophy
Annals of Neurology, 2017Co-Authors: Seward B. Rutkove, Amy Pasternak, Craig M Zaidman, Kush Kapur, Lavanya Madabusi, Sung Yim, Adam Pacheck, Heather Szelag, Tim Harrington, Basil T DarrasAbstract:Objective: Sensitive, objective and easily applied methods for evaluating disease progression and response to therapy are needed for clinical trials in Duchenne muscular dystrophy (DMD). In this study, we evaluated whether electrical impedance Myography (EIM) could serve this purpose. Methods: In this non-blinded study, 36 boys with DMD and 29 age-similar healthy boys underwent multifrequency EIM measurements for up to 2 years on 6 muscles unilaterally along with functional assessments. A linear mixed-effects model with random intercept and slope terms was used for the analysis of multifrequency EIM values and functional measures. Seven DMD boys were initiated on corticosteroids; these data were analyzed using a piecewise linear mixed-effects model. Results: In boys >7.0 years, a significant difference in the slope of EIM phase-ratio trajectories in the upper extremity was observed by 6 months of -0.074/month, p=0.023, 95% confidence interval (CI)[-0.013,-0.14]); at two years, this difference was -0.048/month, p<0.0001 95%CI[-0.028,-0.068]. In boys ≤7.0 years, differences appeared at 6 months in gastrocnemius (EIM phase-slope -0.83°/kHz-month, p=0.007 95%CI[-0.26,-1.40]). EIM outcomes showed significant differences earlier than functional tests. Initiation of corticosteroids significantly improved the slope of EIM phase-ratio (0.057/month, p=0.00019 95%CI[0.028,0.086]) and EIM phase-slope (0.14°/kHz-month, p=0.013 95%CI[0.028,0.25]), consistent with corticosteroids' known clinical benefit. Interpretation: EIM detects deterioration in muscles of both younger and older boys by 6 months; it also identifies the therapeutic effect of corticosteroid initiation. Since EIM is rapid to apply, painless, and requires minimal operator training, the technique deserves to be further evaluated as a biomarker in DMD clinical therapeutic trials. This article is protected by copyright. All rights reserved.
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optimizing electrical impedance Myography measurements by using a multifrequency ratio a study in duchenne muscular dystrophy
Clinical Neurophysiology, 2015Co-Authors: Stefan Schwartz, Tom R Geisbush, Aleksandar S Mijailovic, Amy Pasternak, Basil T Darras, Seward B. RutkoveAbstract:Objective Electrical impedance Myography (EIM) is an electrophysiological technique for neuromuscular evaluation that is impacted by subcutaneous fat (SF). Exploiting the differing frequency dependences of muscle and fat, we assessed a 2-frequency EIM phase ratio in Duchenne muscular dystrophy (DMD) boys.
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cross sectional evaluation of electrical impedance Myography and quantitative ultrasound for the assessment of duchenne muscular dystrophy in a clinical trial setting
Pediatric Neurology, 2014Co-Authors: Seward B. Rutkove, Tom R Geisbush, Aleksandar S Mijailovic, Irina Shklyar, Amy Pasternak, Nicole Visyak, Craig M Zaidman, Basil T DarrasAbstract:Abstract Background Electrical impedance Myography and quantitative ultrasound are two noninvasive, painless, and effort-independent approaches for assessing neuromuscular disease. Both techniques have potential to serve as useful biomarkers in clinical trials in Duchenne muscular dystrophy. However, their comparative sensitivity to disease status and how they relate to one another are unknown. Methods We performed a cross-sectional analysis of electrical impedance Myography and quantitative ultrasound in 24 healthy boys and 24 with Duchenne muscular dystrophy, aged 2 to 14 years with trained research assistants performing all measurements. Three upper and three lower extremity muscles were studied unilaterally in each child, and the data averaged for each individual. Results Both electrical impedance Myography and quantitative ultrasound differentiated healthy boys from those with Duchenne muscular dystrophy ( P P = 0.029), whereas electrical impedance Myography did not (rho = −0.31; P = 0.14). However, electrical impedance Myography phase correlated with age in healthy boys (rho = 0.51; P = 0.012), whereas quantitative ultrasound did not (rho = −0.021; P = 0.92). In Duchenne muscular dystrophy boys, electrical impedance Myography phase correlated with the North Star Ambulatory Assessment (rho = 0.65; P = 0.022); quantitative ultrasound revealed a near-significant association (rho = −0.56; P = 0.060). The two technologies trended toward a moderate correlation with one another in the Duchenne muscular dystrophy cohort but not in the healthy group (rho = −0.40; P = 0.054 and rho = −0.32; P = 0.13, respectively). Conclusions Electrical impedance Myography and quantitative ultrasound are complementary modalities for the assessment of boys with Duchenne muscular dystrophy; further study and application of these two modalities alone or in combination in a longitudinal fashion are warranted.
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electrical impedance Myography in spinal muscular atrophy a longitudinal study
Muscle & Nerve, 2012Co-Authors: Seward B. Rutkove, Matt Gregas, Basil T DarrasAbstract:Introduction: New approaches for assessing disease progression in spinal muscular atrophy (SMA) are needed. In this study, we evaluate whether electrical impedance Myography (EIM) can detect disease progression in SMA compared with a group of healthy children of similar age. Methods: Twenty-eight children with SMA and 20 normal children underwent repeated EIM testing in four muscles at regular intervals for up to 3 years. An average rate of change of EIM was calculated for each subject and normalized to subcutaneous fat thickness and muscle girth. Results: Multiple EIM parameters showed a change in normal subjects over a mean of 16.7 months; however, no change was found in SMA patients over this period. Conclusions: EIM could detect non–mass-dependent muscle maturation in healthy children. In contrast, the muscle in children with SMA, as measured by EIM, was virtually static, showing no evidence of growth or active deterioration. Muscle Nerve, 2012
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characterizing spinal muscular atrophy with electrical impedance Myography
Muscle & Nerve, 2010Co-Authors: Seward B. Rutkove, Jeremy M Shefner, Patricia M Fogerson, Connie Lin, Matt Gregas, Hailly Butler, Jayson Caracciolo, Phillip Mongiovi, Basil T DarrasAbstract:Electrical impedance Myography (EIM) is a non-invasive, painless technique for the evaluation of neuromuscular disease, and here we evaluate its potential application in spinal muscular atrophy (SMA). Twenty-one SMA patients and 18 healthy children underwent EIM of biceps brachii and tibialis anterior using a commercially available impedance device. Hand-held dynamometry and ultrasound assessment of subcutaneous fat thickness were also performed. All EIM parameters differed significantly between both SMA patients and normal subjects and between type 2 and type 3 SMA patients. In addition, EIM had an accuracy level as high as 93% for correctly categorizing patients as type 2 or type 3. Multiple regression analyses confirmed a strong association between EIM and dynamometry. These results confirm that EIM can accurately categorize patients with SMA. Because EIM requires no patient effort and is rapid to apply, it may serve a useful role in future SMA clinical trials.
Carlo Menon - One of the best experts on this subject based on the ideXlab platform.
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towards the investigation on the effect of the forearm rotation on the wrist fmg signal pattern using a high density fmg sensing matrix
Cogent engineering, 2020Co-Authors: Zhen G Xiao, Carlo MenonAbstract:Force Myography (FMG) is an emerging technique to predict extremity movement. The FMG signals captured near the wrist can be used to predict many hand gestures. However, the wrist FMG pattern of a ...
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a review of force Myography research and development
Sensors, 2019Co-Authors: Zhen Gang Xiao, Carlo MenonAbstract:Information about limb movements can be used for monitoring physical activities or for human-machine-interface applications. In recent years, a technique called Force Myography (FMG) has gained ever-increasing traction among researchers to extract such information. FMG uses force sensors to register the variation of muscle stiffness patterns around a limb during different movements. Using machine learning algorithms, researchers are able to predict many different limb activities. This review paper presents state-of-art research and development on FMG technology in the past 20 years. It summarizes the research progress in both the hardware design and the signal processing techniques. It also discusses the challenges that need to be solved before FMG can be used in an everyday scenario. This paper aims to provide new insight into FMG technology and contribute to its advancement.
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regressing grasping using force Myography an exploratory study
Biomedical Engineering Online, 2018Co-Authors: Rana Sadeghi Chegani, Carlo MenonAbstract:Partial hand amputation forms more than 90% of all upper limb amputations. This amputation has a notable effect on the amputee’s life. To improve the quality of life for partial hand amputees different prosthesis options, including externally-powered prosthesis, have been investigated. The focus of this work is to explore force Myography (FMG) as a technique for regressing grasping movement accompanied by wrist position variations. This study can lay the groundwork for a future investigation of FMG as a technique for controlling externally-powered prostheses continuously. Ten able-bodied participants performed three hand movements while their wrist was fixed in one of six predefined positions. The angle between Thumb and Index finger ( $$\theta _{TI}$$ ), and Thumb and Middle finger ( $$\theta _{TM}$$ ) were calculated as measures of grasping movements. Two approaches were examined for estimating each angle: (i) one regression model, trained on data from all wrist positions and hand movements; (ii) a classifier that identified the wrist position followed by a separate regression model for each wrist position. The possibility of training the system using a limited number of wrist positions and testing it on all positions was also investigated. The first approach had a correlation of determination ( $$R^2$$ ) of 0.871 for $$\theta _{TI}$$ and $$R^2_{\theta _{TM}} = 0.941$$ . Using the second approach $$R^2_{\theta _{TI}}=0.874$$ and $$R^2_{\theta _{TM}}=0.942$$ were obtained. The first approach is over two times faster than the second approach while having similar performance; thus the first approach was selected to investigate the effect of the wrist position variations. Training with 6 or 5 wrist positions yielded results which were not statistically significant. A statistically significant decrease in performance resulted when less than five wrist positions were used for training. The results indicate the potential of FMG to regress grasping movement, accompanied by wrist position variations, with a regression model for each angle. Also, it is necessary to include more than one wrist position in the training phase.
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a wearable gait phase detection system based on force Myography techniques
Sensors, 2018Co-Authors: Xianta Jiang, Kelvin Ht Chu, Mahta Khoshnam, Carlo MenonAbstract:(1) Background: Quantitative evaluation of gait parameters can provide useful information for constructing individuals’ gait profile, diagnosing gait abnormalities, and better planning of rehabilitation schemes to restore normal gait pattern. Objective determination of gait phases in a gait cycle is a key requirement in gait analysis applications; (2) Methods: In this study, the feasibility of using a force Myography-based technique for a wearable gait phase detection system is explored. In this regard, a force Myography band is developed and tested with nine participants walking on a treadmill. The collected force Myography data are first examined sample-by-sample and classified into four phases using Linear Discriminant Analysis. The gait phase events are then detected from these classified samples using a set of supervisory rules; (3) Results: The results show that the force Myography band can correctly detect more than 99.9% of gait phases with zero insertions and only four deletions over 12,965 gait phase segments. The average temporal error of gait phase detection is 55.2 ms, which translates into 2.1% error with respect to the corresponding labelled stride duration; (4) Conclusions: This proof-of-concept study demonstrates the feasibility of force Myography techniques as viable solutions in developing wearable gait phase detection systems.
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force exertion affects grasp classification using force Myography
IEEE Transactions on Human-Machine Systems, 2018Co-Authors: Xianta Jiang, Lukaskarim Merhi, Carlo MenonAbstract:This paper describes a study that explores the force exertion effect on the classification of grasps using a force Myography (FMG) technology. Nine participants were recruited to the study; each performed a set of 16 different grasps from a grasp taxonomy using eight different levels of force, respectively. Their wrist muscle pressure was recorded using an array of 16 force sensing resistors. A linear discriminant analysis model was trained by grasps at a single force level using the natural grasping force to classify grasps generated by eight different levels of force. The results show that the grasping force significantly affects the accuracy of grasp classification such that a grasping force closer to the natural force achieves a higher accuracy. A still acceptable classification performance can be achieved for approximately half of the natural grasping force. The findings of this study help the understanding of how force exertion can affect grasp recognition using FMG. Knowledge gained from this study will provide guidance for the implementation of gesture control interfaces in terms of grasping force variations.
Lars Edvinsson - One of the best experts on this subject based on the ideXlab platform.
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Contractile Changes in the Vasculature After Subchronic Smoking: A Comparison Between Wild Type and Surfactant Protein D Knock-Out Mice.
Nicotine & Tobacco Research, 2015Co-Authors: Kristian Agmund Haanes, Lars S Kruse, Helle Wulf-johansson, Christian Støttrup, Grith Lykke Sørensen, Lars EdvinssonAbstract:Introduction: Cigarette smoking is a well-known risk factor for developing cardiovascular diseases, but the underlying mechanisms are largely unknown. Recent data suggest that vasocontractile receptor modulation could be an important factor. Surfactant protein D (SP-D) is important in the particle clearance in the lungs and knock-out (KO) mice for this protein develop emphysema. SP-D is also weakly expressed in the vasculature. We aimed to investigate whether SP-D was important in the cardiovascular response to cigarette smoke exposure (CSE), by utilizing SP-D KO mice and a myograph setup. Methods: Wild type (WT) and SP-D KO mice were exposed to cigarette smoke (CS) or room air for 12 weeks. The pulmonary artery, left anterior descending coronary artery, and basilar artery (BA) were isolated and mounted in wire myographs. Contractile concentration response curves to endothelin-1 and UDP were obtained. Results: CSE caused a leftward shift in the concentration response curves for endothelin-1 in the BA for both WT and SP-D KO. UDP, acting on the purinergic P2Y6 receptor, caused reduced contraction in the left descending artery and increased contraction in the BA in the CSE WT mice. SP-D KO mice displayed no smoke induced changes, but were surprisingly similar to the CSE WT. Conclusion: The contractility to UDP was altered in the brain and heart vasculature of CSE mice. SP-D KO (both control and CSE) and CSE WT had similar changes in contractility compared to control WT. Implications: These results show that sub-chronic smoking induces vascular changes in the WT, mainly for the purinergic P2Y6 receptor together with minor changes for the endothelin-1 receptor. SP-D KO (both control and CSE) does not show any further changes compared to CSE WT.
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dural administration of inflammatory soup or complete freund s adjuvant induces activation and inflammatory response in the rat trigeminal ganglion
Journal of Headache and Pain, 2015Co-Authors: Melinda Lukacs, Zs Majlath, Karin Warfvinge, János Tajti, Kristian Agmund Haanes, Laszlo Vecsei, Lars EdvinssonAbstract:Migraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has previously been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation together with direct activation of the TG. We asked whether local inflammation of dura mater induces inflammatory activation in the trigeminal ganglion. We performed topical administration of inflammatory soup (IS) or Complete Freund’s Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7 days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot. Both CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen in the satellite glial cells, while IL-1β reactivity was observed in the neuronal cytoplasm, close to the cell membrane, seemingly as sign of neuro-glial interaction. The CGRP expression in the neurons and nerve fibres was enhanced after the application of either inflammatory agent. Myography resulted in a strong vasoconstrictor response to IS, but not to CFA. These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system.
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contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat
Journal of Headache and Pain, 2007Co-Authors: Peer Tfelthansen, Elisabeth Nilsson, Lars EdvinssonAbstract:The vasomotor effects of ergotamine and dihydroergotamine (DHE) on the middle cerebral artery (MCA) of rats were studied using the pressurised arteriography method and in vitro myographs. MCAs from Sprague–Dawley rats were mounted on two glass micropipettes using the arteriograph, pressurised to 85 mmHg and luminally perfused. All vessels used attained spontaneous contractile tone (34.9±1.8% of resting tone) and responded to luminal adenosine triphosphate (ATP) with dilatation (24.1±4.0%), which showed functioning endothelium. Luminally added ergotamine or DHE induced maximal contractions of 16.8+8% and 22.4±0.9%, respectively, compared to the resting diameter, with a pEC50 of 8.7±0.1 for ergotamine and 9.0±0.1 for DHE. Abluminal application of ergotamine and DHE also caused concentration-dependent contractions of the perfused MCA by 21.4±2.1% and 23.1±7.0%, respectively, with pEC50 values of 7.6±0.2 for ergotamine and 8.4±0.5 for DHE. The responses were blocked by the 5-HT2A receptor antagonist ketanserin (concentration 10−12 to 10−5 M) and partially with the 5-HT1B receptor antagonist BRL-11557PM-B. The 5-HT1D receptor antagonist SB-224289-A had no significant effect. Using a myograph technique, isolated ring segments of the MCA with intact endothelium were mounted on two metal wires. Neither agonist caused relaxation of resting vessels, however, they both responded by weak contractile responses (26±3% of submaximal contractile capacity relative to 60 mM potassium). The contractions were typically slow in on and off set (about 30–60 min). The long duration of ergots should be investigated further in an attempt to design drugs with less recurrence.
E S Vanzant - One of the best experts on this subject based on the ideXlab platform.
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contractile response of bovine lateral saphenous vein to ergotamine tartrate exposed to different concentrations of molecularly imprinted polymer
Toxins, 2018Co-Authors: Manoj Bojappa Kudupoje, J L Klotz, Alexandros Yiannikouris, Karl A Dawson, K R Mcleod, E S VanzantAbstract:Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo Myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50) (−log [ETA]) of 6.66 ± 0.17 M). Although sample preparation time affected contractile response (p 0.05). Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg−1 and affinity between 0.51 and 0.57 mg (R2: 0.83–0.92) for both polymers, with no significant difference between polymers (p > 0.05). No significant differences in maximum inhibitory (p = 0.96) and IC50 responses (p = 0.163) between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2 = 0.87, p < 0.01), for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media.
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Contractile Response of Bovine Lateral Saphenous Vein to Ergotamine Tartrate Exposed to Different Concentrations of Molecularly Imprinted Polymer
MDPI AG, 2018Co-Authors: Manoj Bojappa Kudupoje, J L Klotz, Alexandros Yiannikouris, Karl A Dawson, K R Mcleod, E S VanzantAbstract:Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo Myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50) (−log [ETA]) of 6.66 ± 0.17 M). Although sample preparation time affected contractile response (p < 0.001), pre-myograph incubation temperature (39 vs. 21 °C, 1 h) had no effect (p > 0.05). Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg−1 and affinity between 0.51 and 0.57 mg (R2: 0.83–0.92) for both polymers, with no significant difference between polymers (p > 0.05). No significant differences in maximum inhibitory (p = 0.96) and IC50 responses (p = 0.163) between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2 = 0.87, p < 0.01), for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media
