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Toxins
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Assessment of Animal Toxin Function with Novel Viscoelastic Methods
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Assessment of Animal Toxin Function with Novel Viscoelastic Methods

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 15111

Special Issue Editor

Prof. Dr. Vance G. Nielsen

E-Mail Website
Guest Editor
Department of Anesthesiology, University of Arizona College of Medicine, Tucson, AZ 85719, USA
Interests: coagulation; thrombelastography; snake venom; heme mediated regulation; heavy metals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This issue will include works that assess the effects of snake or insect venom and other toxins on whole blood or plasmatic coagulation. Venoms typically contain numerous enzymes and compounds, but these biochemical entities all have different kinetic rates of action. Usually one enzyme or class of enzymes will predominate, resulting in a procoagulant or anticoagulant effect. A method of assessment of these venom-mediated effects that is rapidly gaining interest is viscoelastic, which is determined by a thrombelastograph or similar device that records the coagulation kinetics of forming thrombi. By assessing the onset of coagulation, velocity of clot growth and final clot strength, the nature of toxins and the inhibition of toxins by unique inhibitors can be characterized. Of critical interest, some toxins that mediate neurotoxicity also affect coagulation, allowing the opportunity to assess their function with in vitro viscoelastic methods rather than the use of in vivo models that would require animal utilization. In summary, this issue seeks to examine the hemotoxic and by extension neurotoxic effects of venoms with novel viscoelastic and other similar physical chemistry methods.

Prof. Vance G Nielsen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • thrombelastography
  • thromboelastimetry
  • phospholipase
  • metalloproteinase
  • serine protease
  • 3-finger toxin
  • snake venom
  • insect venom
  • neurotoxin

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Published Papers (3 papers)

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Research

11 pages, 1940 KiB  
Article
Factor XII-Deficient Chicken Plasma as a Useful Target for Screening of Pro- and Anticoagulant Animal Venom Toxins
by Benedito C. Prezoto and Nancy Oguiura
Toxins 2020, 12(2), 79; https://doi.org/10.3390/toxins12020079 - 23 Jan 2020
Viewed by 2107
Abstract
The sensitivity of vertebrate citrated plasma to pro- and anticoagulant venom or toxins occurs on a microscale level (micrograms). Although it improves responses to agonists, recalcification triggers a relatively fast thrombin formation process in mammalian plasma. As it has a natural factor XII [...] Read more.
The sensitivity of vertebrate citrated plasma to pro- and anticoagulant venom or toxins occurs on a microscale level (micrograms). Although it improves responses to agonists, recalcification triggers a relatively fast thrombin formation process in mammalian plasma. As it has a natural factor XII deficiency, the recalcification time (RT) of chicken plasma (CP) is comparatively long [≥ 1800 seconds (s)]. Our objective was to compare the ability of bee venom phospholipase A2 (bvPLA2) to neutralize clot formation induced by an activator of coagulation (the aPTT clot) in recalcified human and chicken plasmas, through rotational thromboelastometry. The strategy used in this study was to find doses of bvPLA2 that were sufficient enough to prolong the clotting time (CT) of these activated plasmas to values within their normal RT range. The CT of CP was prolonged in a dose-dependent manner by bvPLA2, with 17 ± 2.8 ng (n = 6) being sufficient to displace the CT values of the activated samples to ≥ 1800 s. Only amounts up to 380 ± 41 ng (n = 6) of bvPLA2 induced the same effect in activated human plasma samples. In conclusion, the high sensitivity of CP to agonists and rotational thromboelastometry could be useful. For example, during screening procedures for assaying the effects of toxins in several stages of the coagulation pathway, such as clot initiation, formation, stability, strength, or dissolution. Full article
(This article belongs to the Special Issue Assessment of Animal Toxin Function with Novel Viscoelastic Methods)
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13 pages, 4661 KiB  
Article
Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage
by James S. Dobson, Christina N. Zdenek, Chris Hay, Aude Violette, Rudy Fourmy, Chip Cochran and Bryan G. Fry
Toxins 2019, 11(5), 255; https://doi.org/10.3390/toxins11050255 - 7 May 2019
Cited by 21 | Viewed by 9165
Abstract
The functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet [...] Read more.
The functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet aggregation as one bleeding-inducing activity, and destructive cleavage of fibrinogen as another. However, the ability of the venoms to prevent clot formation has not been directly investigated. Using a thromboelastograph (TEG5000), clot strength was measured after incubating human fibrinogen with Heloderma and Varanus lizard venoms. Clot strengths were found to be highly variable, with the most potent effects produced by incubation with Varanus venoms from the Odatria and Euprepriosaurus clades. The most fibrinogenolytically active venoms belonged to arboreal species and therefore prey escape potential is likely a strong evolutionary selection pressure. The results are also consistent with reports of profusive bleeding from bites from other notably fibrinogenolytic species, such as V. giganteus. Our results provide evidence in favour of the predatory role of venom in varanid lizards, thus shedding light on the evolution of venom in reptiles and revealing potential new sources of bioactive molecules useful as lead compounds in drug design and development. Full article
(This article belongs to the Special Issue Assessment of Animal Toxin Function with Novel Viscoelastic Methods)
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15 pages, 521 KiB  
Article
De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses
by Vance G. Nielsen, Nathaniel Frank and Sam Afshar
Toxins 2019, 11(2), 94; https://doi.org/10.3390/toxins11020094 - 6 Feb 2019
Cited by 19 | Viewed by 3400
Abstract
Snakebite with hemotoxic venom continues to be a major source of morbidity and mortality worldwide. Our laboratory has characterized the coagulopathy that occurs in vitro in human plasma via specialized thrombelastographic methods to determine if venoms are predominantly anticoagulant or procoagulant in nature. [...] Read more.
Snakebite with hemotoxic venom continues to be a major source of morbidity and mortality worldwide. Our laboratory has characterized the coagulopathy that occurs in vitro in human plasma via specialized thrombelastographic methods to determine if venoms are predominantly anticoagulant or procoagulant in nature. Further, the exposure of venoms to carbon monoxide (CO) or O-phenylhydroxylamine (PHA) modulate putative heme groups attached to key enzymes has also provided mechanistic insight into the multiple different activities contained in one venom. The present investigation used these techniques to characterize fourteen different venoms obtained from snakes from North, Central, and South America. Further, we review and present previous thrombelastographic-based analyses of eighteen other species from the Americas. Venoms were found to be anticoagulant and procoagulant (thrombin-like activity, thrombin-generating activity). All prospectively assessed venom activities were determined to be heme-modulated except two, wherein both CO and its carrier molecule were found to inhibit activity, while PHA did not affect activity (Bothriechis schlegelii and Crotalus organus abyssus). When divided by continent, North and Central America contained venoms with mostly anticoagulant activities, several thrombin-like activities, with only two thrombin-generating activity containing venoms. In contrast, most venoms with thrombin-generating activity were located in South America, derived from Bothrops species. In conclusion, the kinetomic profiles of venoms obtained from thirty-two Pan-American Pit Viper species are presented. It is anticipated that this approach will be utilized to identify clinically relevant hemotoxic venom enzymatic activity and assess the efficacy of locally delivered CO or systemically administered antivenoms. Full article
(This article belongs to the Special Issue Assessment of Animal Toxin Function with Novel Viscoelastic Methods)
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