Characterization of Cholinesterases From Multiple Large Animal Species for Medical Countermeasure Development Against Chemical Warfare Nerve Agents

2019 ◽  
Vol 174 (1) ◽  
pp. 124-132 ◽  
Author(s):  
Kevin G McGarry ◽  
Kevin E Schill ◽  
Tyson P Winters ◽  
Erin E Lemmon ◽  
Carol L Sabourin ◽  
...  
Keyword(s):  
Animal Models ◽  
Cholinergic Neurons ◽  
The United States ◽  
Nerve Agents ◽  
Chemical Warfare ◽  
Cholinesterase Inhibition ◽  
Kinetic Properties ◽  
Large Animal ◽  
Large Animal Models

Abstract Organophosphorus (OP) compounds, which include insecticides and chemical warfare nerve agents (CWNAs) such as sarin (GB) and VX, continue to be a global threat to both civilian and military populations. It is widely accepted that cholinesterase inhibition is the primary mechanism for acute OP toxicity. Disruption of cholinergic function through the inhibition of acetylcholinesterase (AChE) leads to the accumulation of the neurotransmitter acetylcholine. Excess acetylcholine at the synapse results in an overstimulation of cholinergic neurons which manifests in the common signs and symptoms of OP intoxication (miosis, increased secretions, seizures, convulsions, and respiratory failure). The primary therapeutic strategy employed in the United States to treat OP intoxication includes reactivation of inhibited AChE with the oxime pralidoxime (2-PAM) along with the muscarinic acetylcholine receptor antagonist atropine and the benzodiazepine, diazepam. CWNAs are also known to inhibit butyrylcholinesterase (BChE) without any apparent toxic effects. Therefore, BChE may be viewed as a “bioscavenger” that stoichiometrically binds CWNAs and removes them from circulation. The degree of inhibition of AChE and BChE and the effectiveness of 2-PAM are known to vary among species. Animal models are imperative for evaluating the efficacy of CWNA medical countermeasures, and a thorough characterization of available animal models is important for translating results to humans. Thus, the objective of this study was to compare the circulating levels of each of the cholinesterases as well as multiple kinetic properties (inhibition, reactivation, and aging rates) of both AChE and BChE derived from humans to AChE and BChE derived from commonly used large animal models.

scholarly journals Markers for Characterization of Bone Marrow Multipotential Stromal Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sally A. Boxall ◽  
Elena Jones
Keyword(s):  
Bone Marrow ◽  
Animal Models ◽  
Stromal Cells ◽  
Cartilage Tissue ◽  
Proliferative Potential ◽  
Large Animal ◽  
Native Bone ◽  
Large Animal Models

Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs), in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native) bone marrow (BM) MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1) may have the strongest translational value. Whereas small animal models are needed to discover thein vivofunction on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering.

scholarly journals Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence

2021 ◽  
Vol 22 (11) ◽  
pp. 6092
Author(s):  
Bastian Amend ◽  
Niklas Harland ◽  
Jasmin Knoll ◽  
Arnulf Stenzl ◽  
Wilhelm K. Aicher
Keyword(s):  
Urinary Incontinence ◽  
Stress Urinary Incontinence ◽  
Animal Models ◽  
Clinical Situation ◽  
Surgical Instruments ◽  
Health Concern ◽  
Large Animal ◽  
Knock Out ◽  
Cell Therapies ◽  
Large Animal Models

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.

Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes

2017 ◽  
Vol 28 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Lan Huang ◽  
Fengyan Zhao ◽  
Yi Qu ◽  
Li Zhang ◽  
Yan Wang ◽  
...  
Keyword(s):  
Animal Models ◽  
Small Animal ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Large Animal ◽  
Large Animal Models ◽  
Neurological Research ◽  
Serious Disease ◽  
Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models.

Echocardiography Evaluation of a Novel Stable Ovine Heart Failure Model Suitable for Cardiovascular Device Testing

2011 ◽  
Author(s):  
Peter W. Walsh ◽  
Craig S. McLachlan ◽  
Leigh Ladd ◽  
Arie Blitz ◽  
R. Mark Gillies ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Models ◽  
Large Animal ◽  
Failure Model ◽  
Large Animal Models ◽  
Surgical Model ◽  
Coronary Ligation ◽  
Rapid Ventricular Pacing ◽  
Heart Failure Model ◽  
Underlying Pathology

Numerous large animal models of chronic cardiac ischemia have been developed to explore either pathological mechanisms and or device interventions in developed heart failure models. Traditionally chronic heart failure in large animal models such as sheep or pigs has been induced by either coronary ligation with or without reperfusion. Coronary ligation is often attempted in the open chest surgical model or more recently in the closed chest animal via angiography [1]. Both techniques can be challenging and also induce high mortality with the risk of myocardial stunning and resultant shock and or lethal arrhythmias. There is also difficulty in developing stable heart failure across cases where infarct sizes can be variable. One strategy to over come this variability has been via rapid ventricular pacing, however inducing heart failure does not induce sustained heart failure in many cases if the pacing is switched off, and additionally pacing does not induce some of the underlying pathology seen in the development of heart failure [1].

scholarly journals Review: Tissue Engineering of Small-Diameter Vascular Grafts and Their In Vivo Evaluation in Large Animals and Humans

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 713
Author(s):  
Shu Fang ◽  
Ditte Gry Ellman ◽  
Ditte Caroline Andersen
Keyword(s):  
Animal Models ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Large Animal ◽  
Large Animal Models ◽  
Graft Outcome ◽  
Limited Success ◽  
Large Animals

To date, a wide range of materials, from synthetic to natural or a mixture of these, has been explored, modified, and examined as small-diameter tissue-engineered vascular grafts (SD-TEVGs) for tissue regeneration either in vitro or in vivo. However, very limited success has been achieved due to mechanical failure, thrombogenicity or intimal hyperplasia, and improvements of the SD-TEVG design are thus required. Here, in vivo studies investigating novel and relative long (10 times of the inner diameter) SD-TEVGs in large animal models and humans are identified and discussed, with emphasis on graft outcome based on model- and graft-related conditions. Only a few types of synthetic polymer-based SD-TEVGs have been evaluated in large-animal models and reflect limited success. However, some polymers, such as polycaprolactone (PCL), show favorable biocompatibility and potential to be further modified and improved in the form of hybrid grafts. Natural polymer- and cell-secreted extracellular matrix (ECM)-based SD-TEVGs tested in large animals still fail due to a weak strength or thrombogenicity. Similarly, native ECM-based SD-TEVGs and in-vitro-developed hybrid SD-TEVGs that contain xenogeneic molecules or matrix seem related to a harmful graft outcome. In contrast, allogeneic native ECM-based SD-TEVGs, in-vitro-developed hybrid SD-TEVGs with allogeneic banked human cells or isolated autologous stem cells, and in-body tissue architecture (IBTA)-based SD-TEVGs seem to be promising for the future, since they are suitable in dimension, mechanical strength, biocompatibility, and availability.

Production of Adeno-Associated Virus Vectors in Cell Stacks for Preclinical Studies in Large Animal Models

10.3791/62727 ◽  
2021 ◽  
Author(s):  
Amira D. Rghei ◽  
Brenna A. Y. Stevens ◽  
Sylvia P. Thomas ◽  
Jacob G. E. Yates ◽  
Benjamin M. McLeod ◽  
...  
Keyword(s):  
Animal Models ◽  
Large Animal ◽  
Preclinical Studies ◽  
Adeno Associated Virus ◽  
Virus Vectors ◽  
Large Animal Models

Large animal models for the study of ovarian follicular dynamics in women

2012 ◽  
Vol 78 (8) ◽  
pp. 1733-1748 ◽  
Author(s):  
G.P. Adams ◽  
J. Singh ◽  
A.R. Baerwald
Keyword(s):  
Animal Models ◽  
Large Animal ◽  
Large Animal Models ◽  
Follicular Dynamics
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