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Long-sen Chang - One of the best experts on this subject based on the ideXlab platform.
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Modulated mechanism of phosphatidylserine on the catalytic activity of Naja naja atra phospholipase A2 and Notechis scutatus scutatus notexin
Toxicon : official journal of the International Society on Toxinology, 2014Co-Authors: Yiling Chiou, Shinneren Lin, Long-sen ChangAbstract:Phosphatidylserine (PS) externalization is a hallmark for apoptotic death of cells. Previous studies showed that Naja naja atra phospholipase A2 (NnaPLA2) and Notechis scutatus scutatus notexin induced apoptosis of human cancer cells. However, NnaPLA2 and notexin did not markedly disrupt the integrity of cellular membrane as evidenced by membrane permeability of propidium iodide. These findings reflected that the ability of NnaPLA2 and notexin to hydrolyze membrane phospholipids may be affected by PS externalization. To address that question, this study investigated the membrane-interacted mode and catalytic activity of NnaPLA2 and notexin toward outer leaflet (phosphatidylcholine/sphingomyelin/cholesterol, PC/SM/Chol) and inner leaflet (phosphatidylserine/phosphatidylethanolamine/cholesterol, PS/PE/Chol) of plasma membrane-mimicking vesicles. PS incorporation promoted enzymatic activity of NnaPLA2 and notexin on PC and PC/SM vesicles, but suppressed NnaPLA2 and notexin activity on PC/SM/Chol and PE/Chol vesicles. PS incorporation increased the membrane fluidity of PC vesicles but reduced membrane fluidity of PC/SM, PC/SM/Chol and PE/Chol vesicles. PS increased the phospholipid order of all the tested vesicles. Moreover, PS incorporation did not greatly alter the binding affinity of notexin and NnaPLA2 with phospholipid vesicles. Acrylamide quenching studies and trinitrophenylation of Lys residues revealed that membrane-bound mode of notexin and NnaPLA2 varied with the targeted membrane compositions. The fine structure of catalytic site in NnaPLA2 and notexin in all the tested vesicles showed different changes. Collectively, the present data suggest that membrane-inserted PS modulates PLA2 interfacial activity via its effects on membrane structure and membrane-bound mode of NnaPLA2 and notexin, and membrane compositions determine the effect of PS on PLA2 activity.
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notexin upregulates fas and fasl protein expression of human neuroblastoma sk n sh cells through p38 mapk atf 2 and jnk c jun pathways
Toxicon, 2010Co-Authors: Ku Chung Chen, Long-sen ChangAbstract:Abstract Notechis scutatus scutatus notexin induced an increase in Fas and FasL protein expression of human neuroblastoma SK-N-SH cells in a dose- and time-dependent manner. Moreover, notexin treatment upregulated transcription of Fas/FasL mRNA. Downregulation of FADD blocked notexin-induced procaspase-8 degradation and cleavage of Bid and rescued viability of notexin-treated cells. Upon exposure to notexin, activation of JNK and p38 MAPK was observed in SK-N-SH cells. Notexin-induced upregulation of Fas and FasL was suppressed by SB202190 (p38 MAPK inhibitor) and S600125 (JNK inhibitor). Downregulation of p38α MAPK and JNK1 by siRNA proved that upregulation of Fas/FasL was related to p38α MAPK and JNK1 activation. Notexin treatment evoked p38α MAPK-mediated ATF-2 phosphorylation and JNK1-mediated c-Jun phosphorylation. Knockdown of c-Jun and ATF-2 by siRNA or overexpression of dominant-negative c-Jun and ATF-2 revealed that both c-Jun and ATF-2 were crucial for Fas/FasL upregulation. Taken together, our data indicate that notexin-induced upregulation of Fas and FasL is triggered by p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways in SK-N-SH cells.
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calcium stimulated mitogen activated protein kinase activation elicits bcl xl downregulation and bak upregulation in notexin treated human neuroblastoma sk n sh cells
Journal of Cellular Physiology, 2010Co-Authors: Ku Chung Chen, Peihsiu Kao, Wen Hsin Liu, Long-sen ChangAbstract:Notechis scutatus scutatus notexin induced apoptotic death of SK-N-SH cells accompanied with downregulation of Bcl-xL, upregulation of Bak, mitochondrial depolarization, and ROS generation. Upon exposure to notexin, Ca(2+)-mediated JNK and p38 MAPK activation were observed in SK-N-SH cells. Production of ROS was a downstream event followed by Ca(2+)-mediated mitochondrial alteration. Notexin-induced cell death, mitochondrial depolarization, and ROS generation were suppressed by SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor). Moreover, phospho-p38 MAPK and phospho-JNK were proved to be involved in Bcl-xL degradation, and overexpression of Bcl-xL attenuated the cytotoxic effect of notexin. Bak upregulation was elicited by p38 MAPK-mediated ATF-2 activation and JNK-mediated c-Jun activation. Suppression of Bak upregulation by ATF-2 siRNA or c-Jun siRNA attenuated notexin-evoked mitochondrial depolarization and rescued viability of notexin-treated cells. Taken together, our data indicate that notexin-induced apoptotic death of SK-N-SH cells is mediated through mitochondrial alteration triggering by Ca(2+)-evoked p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways.
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Chemical modification of arginine residues of Notechis scutatus scutatus notexin.
Toxicon : official journal of the International Society on Toxinology, 2004Co-Authors: Long-sen Chang, Jau-cheng Liou, Wen-hsien Chiang-lin, Chen-chung YangAbstract:Notexin, a presynaptic phospholipase A2 (PLA2) neurotoxin isolated from Notechis scutatus scutatus venom, was inactivated by arginine-specific reagents, phenylglyoxal and 1,2-cyclohexanedione. Kinetic analyses of the modification reaction revealed that the inactivation of notexin followed pseudo-first order kinetics and the loss of PLA2 activity was correlated with the incorporation of one molecule of modification reagent per toxin molecule. However, the results of amino acid analysis and sequence determination revealed that two arginine residues at positions 43 and 79 of notexin were modified simultaneously. Modification of the arginine residues was accompanied with a decrease in the ability to inhibit the indirectly evoked contraction of chick biventer cervicis muscle and bind with synaptic membranes. The secondary structure of the toxin molecule did not significantly change after modification with phenylglyoxal as revealed by the CD spectra. The modified derivative retained its affinity for Ca2+, indicating that the modified arginine residues did not participate in Ca2+ -binding. Together with the notion that Arg-43 and Arg-79 of notexin are located in the proximity of its catalytic site and toxic site, respectively, our results suggest that modification of Arg-43 and Arg-79 should differently contribute to the observed decrease in the PLA2 activity and neurotoxic effect of notexin.
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chemical modification of notexin from Notechis scutatus scutatus australian tiger snake venom with pyridoxal 5 phosphate
Journal of Protein Chemistry, 1996Co-Authors: Long-sen ChangAbstract:Notexin fromNotechis scutatus scutatus snake venom was subjected to Lys modification with pyridoxal 5′-phosphate (PLP), and one major modified derivative was purified on a cation-exchanger SP-8HR column. The results of amino acid analysis and sequence determination revealed that only 2 Lys residues at positions 82 and 115 out of 11 Lys residues in notexin were modified. The incorporation of PLP into the protein was accompanied by the loss of 53% lethal toxicity, but the modified notexin showed an about 1.2-fold increase in enzymatic activity. However, the secondary structure of the toxin molecule did not significantly change after modification with PLP as revealed by the CD spectra, and the antigenicity of PLP derivative remained unchanged. The modified derivative retained its affinity for Ca2+, indicating that the modified Lys residues did not participate in Ca2+ binding. These results indicate that modification of Lys residues causes a differential effect on the enzymatic activity and lethal toxicity of notexin, and suggest that notexin might possess two functional sites, one responsible for the catalytic activity and the other associated with its lethal effect.
Ivan I. Kaiser - One of the best experts on this subject based on the ideXlab platform.
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Toxins isolated from the venom of the brazilian coral snake (Micrurus frontalis frontalis) include hemorrhagic type phospholipases A2 and postsynaptic neurotoxins
Toxicon : official journal of the International Society on Toxinology, 1997Co-Authors: Brian R. Francis, Nelson Jorge Da Silva, Luciana Lyra Casais-e-silva, Corrine Seebart, James J. Schmidt, Ivan I. KaiserAbstract:Toxins isolated from the venom of the Brazilian coral snake (Micrurus frontalis frontalis) include hemorrhagic type phospholipases A2 and postsynaptic neurotoxins. Toxicon 35, 1193-1203, 1997.-Two sets of proteins have been purified from the venom of the Brazilian coral snake, Micrurus frontalis frontalis. One set has mol. wts, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), in the 8000-13,000 range and includes some proteins which are toxic to mice and others which are not. These proteins appear to be isoforms of postsynaptic toxins. The other set shows phospholipase A2 (PLA2) activity and the toxic members of this set promote hemorrhage in mice in a manner closely resembling that produced by PLA2s isolated from the venom of the Australian tiger snake (Notechis scutatus scutatus). These PLA2s migrate on SDS-PAGE with apparent mol. wts in the 18,000-22,000 range which is characteristic of PLA2s that have an alpha-helix D similar to pancreatic PLA2s. Elapid venom PLA2s of the type which typically migrate on SDS-PAGE with mol. wts in the 13,000-16,000 range and do not have alpha-helix D have not been detected in M. f. frontalis venom.
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Amino Acid Sequence of a New Type of Toxic Phospholipase A2 from the Venom of the Australian Tiger Snake (Notechis scutatus scutatus)
Archives of biochemistry and biophysics, 1995Co-Authors: B. Francis, J.a. Coffield, Lance L. Simpson, Ivan I. KaiserAbstract:Abstract Venom from the common tiger snake, Notechis scutatus scutatus , contains several toxic acidic proteins which promote hypotension and hemorrhage in mice. One of these toxins, HT e , has a phospholipase A 2 (PLA 2 ) amino acid sequence. It contains 125 amino acids rather than the 119/120 found in other N. s. scutatus PLA 2 s, because it also has the loop of residues (62-66) found in helix D of pancreatic PLA 2 s, the γ-subunit of taipoxin, and the D-subunit of textilotoxin. High sequence identity is found between the first 57 and the last 25 amino acids of HT e and other N. s. scutatus PLA 2 s. In the central section containing the pancreatic loop and the β-wing, sequence similarity with other N. s. scutatus PLA 2 s is low. The β-wing amino acids are highly homologous to taipoxin-γ. HT g , an isoform of HT e , has a sequence almost identical to that of HT e in the central section. Neuropharmacological and neurophysiological studies show that HT e blocks neuromuscular transmission, but it does not produce blockade by virtue of a selective action on nerve endings. Instead, the toxin acts both on nerve and on muscle. Unlike taipoxin-γ and textilotoxin-D, HT e and HT g are not glycosylated and are not otherwise modified. HT e , HT g , and the other acidic proteins hydrolyze the synthetic PLA 2 substrate, 3-octanoyloxy-4-nitrobenzoic acid, as well as L-α-phosphatidylcholine.
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Proteins isolated from the venom of the common tiger snake (Notechis scutatus scutatus) promote hypotension and hemorrhage
Toxicon : official journal of the International Society on Toxinology, 1993Co-Authors: Brian R. Francis, Corrine Seebart, Elizabeth S. Williams, Ivan I. KaiserAbstract:Notechis scutatus scutatus venom contains several toxic acidic proteins called HTa-i which promote hypotension and hemorrhage in mice. They have apparent mol. wts in the 18,000-21,000 range, i.v. LD50 values between 0.5 and 1.5 micrograms/g, and no detectable phospholipase, arginine esterase, proteolytic or hemolytic activities. A polyclonal antibody raised against HTg binds to other purified proteins, suggesting that they are isoforms of the same protein. Many other elapid crude venoms contain proteins which recognize the polyclonal antibody raised against HTg. Crotalid and viperid crude venoms do not recognize this antibody, although some of their component proteins are known to exhibit hypotensive and hemorrhagic activities. A combination of gel-filtration on Sephacryl S-200, cation-exchange and anion-exchange chromatography allows isolation of the N. s. scutatus proteins in high purity. They are the first hypotension-inducing proteins to be purified from an Australian elapid.
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New toxins from the venom of the common tiger snake (Notechis scutatus scutatus)
Toxicon : official journal of the International Society on Toxinology, 1991Co-Authors: Brian R. Francis, Ted R. John, Corrine Seebart, Ivan I. KaiserAbstract:Abstract Scutoxin A and B represent two isoforms of a new toxic protein from the venom of the Australian tiger snake, Notechis scutatus scutatus. Both isoforms, of apparent mol. wt 13,000, are less basic than either notexin or Notechis II-5. They both have similar i.v. ld 50-values in mice of ca 0.006 μg/g, and phospholipase activities of about 136 μmoles of fatty acid released /min/mg at 37°C when acting on phosphatidylcholine in the presence of Triton X-100. Toxicities of the scutoxins are the same as notexin and about seven times more potent than Notechis II-5. ELISAs and western blot analyses indicate that the new toxins are immunologically similar to notexin and Notechis II-5, with phospholipase activities falling between these latter two proteins. When crude venom is initially passed over a gel filtration column, each scutoxin isoform co-elutes in a different fraction with notexin. Gel filtration experiments using purified samples of notexin and scutoxin have failed to demonstrate any evidence for the formation of higher mol. wt protein complexes. Peptide mapping suggests the presence of five glutamate residues in one of the protein isoforms. These findings, together with the high toxicity and active phospholipase levels, demonstrate that the new proteins are not the previously reported non-toxic and enzymatically inactive Notechis II-1. The combination of gel filtration on Sephacryl S-200 and cation-exchange chromatography used to isolate the scutoxins also permits recovery of notexin and Notechis II-5 in high purity.
Gutiérrez, José María - One of the best experts on this subject based on the ideXlab platform.
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Lemnitoxin, the major component of Micrurus lemniscatus coral snake venom, is a myotoxic and pro-inflammatory phospholipase A2
2016Co-Authors: Casais Silva, Luciana E Lyra, Teixeira, Catarina De Fátima, Lebrun Ivo, Alape Girón Alberto, Gutiérrez, José MaríaAbstract:The venom of Micrurus lemniscatus, a coral snake of wide geographical distribution in South America, was fractionated by reverse-phase HPLC and the fractions screened for phospholipase A2 (PLA2) activity. The major component of the venom, a PLA2, here referred to as ‘Lemnitoxin’, was isolated and characterized biochemically and toxicologically. It induces myotoxicity upon intramuscular or intravenous injection into mice. The amino acid residues Arg15, Ala100, Asn108, and a hydrophobic residue at position 109, which are characteristic of myotoxic class I phospholipases A2, are present in Lemnitoxin. This PLA2 is antigenically related to M. nigrocinctus nigroxin, Notechis scutatus notexin, Pseudechis australis mulgotoxin, and Pseudonaja textilis textilotoxin, as demonstrated with monoclonal and polyclonal antibodies. Lemnitoxin is highly selective in its targeting of cells, being cytotoxic for differentiated myotubes in vitro and muscle fibers in vivo, but not for undifferentiated myoblasts or endothelial cells. Lemnitoxin is not lethal after intravenous injection at doses up to 2 μg/g in mice, evidencing its lack of significant neurotoxicity. Lemnitoxin displays anticoagulant effect on human plasma and proinflammatory activity also, as it induces paw edema and mast cell degranulation. Thus, the results of this work demonstrate that Lemnitoxin is a potent myotoxic and proinflammatory class I PLA2.International Centre for Genetic Engineering and Biotechnology/[CRP/COS13-01]/ICGEB/ItaliaUniversidad de Costa Rica/[741-B4-100]/UCR/Costa RicaUCR::Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP
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Lemnitoxin, the major component of Micrurus lemniscatus coral snake venom, is a myotoxic and pro-inflammatory phospholipase A2
'Elsevier BV', 2016Co-Authors: Casais Silva, Luciana E Lyra, Teixeira, Catarina De Fátima, Lebrun Ivo, Alape Girón Alberto, Lomonte Bruno, Gutiérrez, José MaríaAbstract:The venom of Micrurus lemniscatus, a coral snake of wide geographical distribution in South America, was fractionated by reverse-phase HPLC and the fractions screened for phospholipase A2 (PLA2) activity. The major component of the venom, a PLA2, here referred to as ‘Lemnitoxin’, was isolated and characterized biochemically and toxicologically. It induces myotoxicity upon intramuscular or intravenous injection into mice. The amino acid residues Arg15, Ala100, Asn108, and a hydrophobic residue at position 109, which are characteristic of myotoxic class I phospholipases A2, are present in Lemnitoxin. This PLA2 is antigenically related to M. nigrocinctus nigroxin, Notechis scutatus notexin, Pseudechis australis mulgotoxin, and Pseudonaja textilis textilotoxin, as demonstrated with monoclonal and polyclonal antibodies. Lemnitoxin is highly selective in its targeting of cells, being cytotoxic for differentiated myotubes in vitro and muscle fibers in vivo, but not for undifferentiated myoblasts or endothelial cells. Lemnitoxin is not lethal after intravenous injection at doses up to 2 μg/g in mice, evidencing its lack of significant neurotoxicity. Lemnitoxin displays anticoagulant effect on human plasma and proinflammatory activity also, as it induces paw edema and mast cell degranulation. Thus, the results of this work demonstrate that Lemnitoxin is a potent myotoxic and proinflammatory class I PLA2.International Centre for Genetic Engineering and Biotechnology/[CRP/COS13-01]/ICGEB/ItaliaUniversidad de Costa Rica/[741-B4-100]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP
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A Lys49-PLA2 myotoxin of Bothrops asper triggers a rapid death of macrophages that involves autocrine purinergic receptor signaling
Cell Death and Disease (2012) 3 e343, 2012Co-Authors: Tonello F., Gutiérrez, José María, Simonato M., Aita A., Pizzo Paola, Fernández Julián, Montecucco CesareAbstract:Cell Death and Disease (2012) 3, e343; doi:10.1038/cddis.2012.68Lys49-PLA2 myotoxins, an important component of various viperid snake venoms, are a class of PLA2-homolog proteins deprived of catalytic activity. Similar to enzymatically active PLA2 (Asp49) and to other classes of myotoxins, they cause severe myonecrosis. Moreover, these toxins are used as tools to study skeletal muscle repair and regeneration, a process that can be very limited after snakebites. In this work, the cytotoxic effect of different myotoxins, Bothrops asper Lys49 and Asp49-PLA2, Notechis scutatus notexin and Naja mossambica cardiotoxin, was evaluated on macrophages, cells that have a key role in muscle regeneration. Only the Lys49-myotoxin was found to trigger a rapid asynchronous death of mouse peritoneal macrophages and macrophagic cell lines through a process that involves ATP release, ATP-induced ATP release and that is inhibited by various purinergic receptor antagonists. ATP leakage is induced also at sublytical doses of the Lys49-myotoxin, it involves Ca2þ release from intracellular stores, and is reduced by inhibitors of VSOR and the maxi-anion channel. The toxin-induced cell death is different from that caused by high concentration of ATP and appears to be linked to localized purinergic signaling. Based on present findings, a mechanism of cell death is proposed that can be extended to other cytolytic proteins and peptides.Universidad de Costa RicaUCR::Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP
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A Lys49-PLA2 myotoxin of Bothrops asper triggers a rapid death of macrophages that involves autocrine purinergic receptor signaling
'Springer Science and Business Media LLC', 2012Co-Authors: Tonello Fiorella, Gutiérrez, José María, Simonato M., Aita A., Pizzo Paola, Fernández Ulate Julián, Lomonte Bruno, Montecucco CesareAbstract:Cell Death and Disease (2012) 3, e343; doi:10.1038/cddis.2012.68Lys49-PLA2 myotoxins, an important component of various viperid snake venoms, are a class of PLA2-homolog proteins deprived of catalytic activity. Similar to enzymatically active PLA2 (Asp49) and to other classes of myotoxins, they cause severe myonecrosis. Moreover, these toxins are used as tools to study skeletal muscle repair and regeneration, a process that can be very limited after snakebites. In this work, the cytotoxic effect of different myotoxins, Bothrops asper Lys49 and Asp49-PLA2, Notechis scutatus notexin and Naja mossambica cardiotoxin, was evaluated on macrophages, cells that have a key role in muscle regeneration. Only the Lys49-myotoxin was found to trigger a rapid asynchronous death of mouse peritoneal macrophages and macrophagic cell lines through a process that involves ATP release, ATP-induced ATP release and that is inhibited by various purinergic receptor antagonists. ATP leakage is induced also at sublytical doses of the Lys49-myotoxin, it involves Ca2þ release from intracellular stores, and is reduced by inhibitors of VSOR and the maxi-anion channel. The toxin-induced cell death is different from that caused by high concentration of ATP and appears to be linked to localized purinergic signaling. Based on present findings, a mechanism of cell death is proposed that can be extended to other cytolytic proteins and peptides.Universidad de Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP
Kenneth D Winkel - One of the best experts on this subject based on the ideXlab platform.
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coagulation factor activity patterns of venom induced consumption coagulopathy in naturally occurring tiger snake Notechis scutatus envenomed dogs treated with antivenom
Toxicon, 2020Co-Authors: Louis Mark Eramanis, A M Padula, Kenneth D Winkel, Andrew P Woodward, Natalie Courtman, Dez Hughes, Manuel BollerAbstract:Abstract Background Venom-induced consumption coagulopathy (VICC) from tiger snake (Notechis scutatus) envenomation results in a dose-dependent coagulopathy that is detectable on coagulometry. However, individual coagulation factor activities in dogs with tiger snake envenomation have not been determined. This study aimed to characterise VICC and the time course of recovery in tiger snake envenomed dogs and to investigate an association between tiger snake venom (TSV) concentrations and factor activity. Methods This was a prospective, observational, cohort study. The study cohort was 11 dogs of any age, breed, sex, body weight >10 kg, confirmed serum TSV on ELISA and treated with antivenom. Blood was collected at enrolment before antivenom administration, then at 3, 12 and 24 h after antivenom administration. Tiger snake venom concentrations were detected with a sandwich ELISA. Fibrinogen was measured using a modified Clauss method, and coagulation factors (F) II, V, VII, VIII and X were measured with factor-deficient human plasma using a modified prothrombin (PT) and activated partial thromboplastin (aPTT) method. Linear mixed models, with multiple imputations of censored observations, were used to determine the effect of time and TSV concentration on the coagulation times and factor activity. This cohort was compared to 20 healthy controls. Results At enrolment, there were severe deficiencies in fibrinogen, FV and FVIII, with predicted recovery by 10.86, 11.75 and 13.14 h after antivenom, respectively. There were modest deficiencies in FX and FII, with predicted recovery by 20.57 and 32.49 h after antivenom, respectively. No changes were detected in FVII. Prothrombin time and aPTT were markedly prolonged with predicted recovery of aPTT by 12.58 h. Higher serum TSV concentrations were associated with greater deficiencies in FII, FV and FVIII, and greater prolongations in coagulation times. The median (range) serum TSV concentration was 57 (6–2295) ng/mL. Conclusions In tiger snake envenomed dogs, we detected a profound, TSV-concentration-related consumption of select coagulation factors, that rapidly recovered toward normal. These findings allowed further insight into tiger snake VICC in dogs.
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successful use of camelid alpaca antivenom to treat a potentially lethal tiger snake Notechis scutatus envenomation in a dog
Toxicon, 2016Co-Authors: A M Padula, Kenneth D WinkelAbstract:This report describes a confirmed clinical case of tiger snake (Notechis scutatus) envenomation in a domestic dog that was successfully treated with a novel polyvalent camelid (alpaca; Llama pacos) antivenom. Samples collected from the dog were assayed for tiger snake venom (TSV) using a highly sensitive and specific ELISA. The TSV concentration in serum and urine at initial presentation was 365 ng/mL and 11,640 ng/mL respectively. At the time of initial presentation whole blood collected from the dog did not clot and the Prothrombin Time was abnormally increased (>300 s). Serum was also visibly hemolysed. The dog was administered antihistamine, dexamethasone and 4000 Units (sufficient to neutralise 40 mg of TSV) of a novel polyvalent alpaca antivenom diluted in 0.9% NaCl. At 4 h post-antivenom treatment the dog's clinical condition had improved markedly with serum TSV concentrations below the limit of detection (<0.015 ng/mL), consistent with complete binding of venom antigens by the alpaca antivenom. Coagulation parameters had begun to improve by 4 h and had fully normalised by 16 h post-antivenom. Venom concentrations in both serum and urine remained undetectable at 16 h post-antivenom. The dog made a complete recovery, without complications, suggesting that the alpaca-based antivenom is both clinically safe and effective.
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fatal presumed tiger snake Notechis scutatus envenomation in a cat with measurement of venom and antivenom concentration
Toxicon, 2016Co-Authors: A M Padula, Kenneth D WinkelAbstract:A fatal outcome of a presumed tiger snake (Notechis scutatus) envenomation in a cat is described. Detectable venom components and antivenom concentrations in serum from clotted and centrifuged whole blood and urine were measured using a sensitive and specific ELISA. The cat presented in a paralysed state with a markedly elevated serum CK but with normal clotting times. The cat was treated with intravenous fluids and received two vials of equine whole IgG bivalent (tiger and brown snake) antivenom. Despite treatment the cat's condition did not improve and it died 36 h post-presentation. Serum concentration of detectable tiger snake venom components at initial presentation was 311 ng/mL and urine 832 ng/mL, this declined to non-detectable levels in serum 15-min after intravenous antivenom. Urine concentration of detectable tiger snake venom components declined to 22 ng/mL at post-mortem. Measurement of equine anti-tiger snake venom specific antibody demonstrated a concentration of 7.2 Units/mL in serum at post-mortem which had declined from an initial high of 13 Units/mL at 15-min post-antivenom. The ELISA data demonstrated the complete clearance of detectable venom components from serum with no recurrence in the post-mortem samples. Antivenom concentrations in serum at initial presentation were at least 100-fold higher than theoretically required to neutralise the circulating concentrations of venom. Despite the fatal outcome in this case it was concluded that this was unlikely that is was due to insufficient antivenom.
Don Bradshaw - One of the best experts on this subject based on the ideXlab platform.
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Which proximate factor determines sexual size dimorphism in tiger snakes
2011Co-Authors: Xavier Bonnet, Fabien Aubret, David Pearson, Don Bradshaw, Sophie Lorioux, Virginie Delmas, Thomas FauvelAbstract:Diverse interactions between factors that influence body size complicate the identification of the primary determinants of sexual size dimorphism. Using data from a long-term field study (1997–2009), we examined the contributions of the main proximate factors potentially influencing sexual size dimorphism from birth to adulthood in tiger snakes (Notechis scutatus). Data on body size, body mass and body condition of neonates, juveniles and adults were obtained by mark–recapture. Frequent recaptures allowed us to monitor reproductive status, diet and food intake, and to estimate survival and growth rates in age and sex classes. Additional data from females held briefly in captivity enabled us to assess reproductive output and the body mass lost at parturition (proxies for reproductive effort). From birth to maturity, individuals of both sexes experienced similar growth and mortality rates. We found no difference in diet, feeding and survival rates between the sexes, nor between juveniles and adults. On maturity, despite comparable diet and food intake by both sexes, the high energy requirements of vitellogenesis and gestation were responsible for a depletion of body reserves and probably resulted in a marked decrease in growth rates. Males were largely exempt from such costs of reproduction, and so could grow faster than females and attain larger body sizes. The absence of niche divergence between the sexes (uniformity of habitat, lack of predators) suggests that the impact of differential energetic investment for reproduction on growth rate is probably the main proximate factor influencing sexual size dimorphism in this species. © 2011 The Linnea
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food versus risk foraging decision in young tiger snakes Notechis scutatus
Amphibia-reptilia, 2007Co-Authors: Don Bradshaw, Xavier Bonnet, Fabien AubretAbstract:Foraging behaviour is influenced by an animal's level of hunger, and may reflect a trade-off between optimizing food acquisition and avoiding predation. Young tiger snakes were raised either on a high or low food diet and exposed to a predation threat while foraging. Under these circumstances, lower condition snakes (low food diet) were prone to take additional feeding/foraging risks: food was accepted at a much higher rate compared with the higher condition animals (high food diet) that were less inclined to risk feeding under a predation threat. This study provides the first direct example of predation risk-associated foraging decisions in snakes.
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Physiological and hormonal control of thermal depression in the tiger snake, Notechis scutatus
Journal of Comparative Physiology B, 2006Co-Authors: Mitchell Ladyman, Don Bradshaw, Felicity BradshawAbstract:Plasma sodium concentrations in field-caught Western tiger snakes, Notechis scutatus , from semi-arid Carnac Island (CI) varied seasonally, with snakes exhibiting significant hypernatraemia during summer and normal concentrations following autumn rain. In contrast, field-caught tiger snakes from a perennial fresh-water swamp (Herdsman Lake, HL) exhibited no significant increase in plasma sodium concentrations during summer. Laboratory-induced hypernatraemia caused thermal depression in both populations; there was a weak negative relationship between plasma sodium concentration and temperature selection that was significant for CI snakes. Hypernatraemia significantly elevated circulating concentrations of the neuropeptide arginine vasotocin (AVT) in both CI and HL snakes. CI snakes injected with a physiological dosage of AVT also evidenced thermal depression. Despite the positive correlation between AVT and both plasma sodium concentration and osmolality for laboratory snakes, field samples from CI snakes indicate that circulating levels of AVT may be influenced more by plasma osmolality than sodium levels. The data suggest that, in CI snakes, chronic dehydration in the field leads to hypernatraemia which may lead to elevated levels of AVT if plasma osmolality also increases. This will in turn invoke a depression in thermal behaviour that may improve the water economy and survival of snakes on semi-arid CI. Although HL snakes do not experience seasonal dehydration, physiological changes away from the stable homeostatic state appear to prompt the same behavioural shifts, illustrating the intrinsic nature of the thermal behaviour in different populations of the same species of snake.
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Feeding preferences in 2 disjunct populations of tiger snakes, Notechis scutatus (Elapidae)
Behavioral Ecology Behavioural Ecology, 2006Co-Authors: Fabien Aubret, Xavier Bonnet, Stéphanie Maumelat, Gordon M. Burghardt, Don BradshawAbstract:Variations at both the genetic and phenotypic levels play an important role in responses to food and food-related stimuli. Knowledge of such variations is crucial to understanding how populations adapt to changing environments. We investigated the dietary preferences of 2 tiger snake populations and compared the responses of diet-naive animals (laboratory-born neonates), diet-controlled animals (laboratory-reared juveniles), and natural diet–experienced animals (wild-caught adults) to visual and chemical cues from 6 prey types (mouse, skink, silver gull, chicken, shearwater, and frog). The mainland population inhabits a swamp, feeds mostly on frogs, and suffers heavy predation. The second population inhabits a small nearby offshore island with no standing water (no frogs); feeds mostly on skinks, mice, and, as adults, silver gull chicks; and suffers no known predation. Although different prey are eaten in the 2 populations, adult wild-caught snakes from both populations showed a significant preference for 3 types of prey (frog, mouse, and chick), irrespective of their natural diet. Neonates responded to all prey cues more than they did to control stimuli in both populations. However, the island neonates showed significantly higher interest in silver gull chick stimuli (the main prey of the island adult snakes) than did their mainland conspecifics. Laboratory-bred juveniles displayed behavioral plasticity by significantly increasing their response to mice after being fed baby mice for 7 months. We conclude that genetic-based differences in food-related cues are important in tiger snakes but that they are also capable of behavioral plasticity. Island adult and neonate snakes exhibited responses to prey types no longer consumed naturally (frog), suggesting that behavioral characters may have been retained for long periods under relaxed selection. Island neonates showed a strong interest in a novel prey item (silver gull). This result complements previous work describing how island snakes have developed the ability to swallow larger prey than usual, as well as seemingly developing a taste for them.
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Diet divergence, jaw size and scale counts in two neighbouring populations of tiger snakes (Notechis scutatus)
Amphibia-Reptilia, 2004Co-Authors: Fabien Aubret, Xavier Bonnet, Stéphanie Maumelat, Don Bradshaw, Terry SchwanerAbstract:Large snakes usually possess a higher number of scales to cover their larger bodies and their larger heads. It has been suggested that a diet based on large prey items also favours the development of scale number because the skin would be more extensible and would enable easier swallowing of voluminous prey. A recent study, however, suggested that although body size positively in uences scale count in snakes, diet is probably unimportant (Shine, 2002). We took advantage of a natural experiment that separated two neighbouring and genetically indistinguishable populations of tiger snakes in the vicinity of Perth, Western Australia. In one population, situated on a small coastal Island (Carnac Island), snakes feed primarily on seagull chicks (large prey). In the second population, located on the mainland (Herdsman Lake), snakes feed mostly on frogs (small prey). Carnac Island snakes possess more scales (labial and mid-body rows) and larger relative jaw lengths compared with Herdsman Lake snakes. Although preliminary, these data suggest that tiger snakes, whose many populations show contrasted feeding habits, are suitable models to test the “dietary habits / scale count” hypothesis.
