https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38528 Wed 27 Oct 2021 16:09:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45245 Daboia russelii) venom causes a range of clinical effects in humans. Hypotension is an uncommon but severe complication of Russell’s viper envenoming. The mechanism(s) responsible for this effect are unclear. In this study, we examined the cardiovascular effects of Sri Lankan D. russelii venom in anaesthetised rats and in isolated mesenteric arteries. D. russelii venom (100 µg/kg, i.v.) caused a 45 ± 8% decrease in blood pressure within 10 min of administration in anaesthetised (100 µg/kg ketamine/xylazine 10:1 ratio, i.p.) rats. Venom (1 ng/mL–1 µg/mL) caused concentration-dependent relaxation (EC₅₀ = 145.4 ± 63.6 ng/mL, R_max = 92 ± 2%) in U46619 pre-contracted rat small mesenteric arteries mounted in a myograph. Vasorelaxant potency of venom was unchanged in the presence of the nitric oxide synthase inhibitor, L-NAME (100 µM), or removal of the endothelium. In the presence of high K⁺ (30 mM), the vasorelaxant response to venom was abolished. Similarly, blocking voltage-dependent (K_v: 4-aminopryidine; 1000 µM) and Ca²⁺-activated (K_Ca: tetraethylammonium (TEA; 1000 µM); SK_Ca: apamin (0.1 µM); IK_Ca: TRAM-34 (1 µM); BK_Ca; iberiotoxin (0.1 µM)) K⁺ channels markedly attenuated venom-induced relaxation. Responses were unchanged in the presence of the ATP-sensitive K⁺ channel blocker glibenclamide (10 µM), or H1 receptor antagonist, mepyramine (0.1 µM). Venom-induced vasorelaxtion was also markedly decreased in the presence of the transient receptor potential cation channel subfamily V member 4 (TRPV4) antagonist, RN-1734 (10 µM). In conclusion, D. russelii-venom-induced hypotension in rodents may be due to activation of K_v and K_Ca channels, leading to vasorelaxation predominantly via an endothelium-independent mechanism. Further investigation is required to identify the toxin(s) responsible for this effect.]]> Wed 26 Oct 2022 19:42:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14373 Wed 11 Apr 2018 10:50:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14544 Wed 11 Apr 2018 10:15:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44896 98% amino acid sequence similarity with short-chain postsynaptic neurotoxins from other Naja species. When compared to short-chain neurotoxins isolated from cobras in China, α-EPTX-Na1a contained novel residues K47Q (i.e. lysine to glutamine), N48T (i.e. asparagine to threonine) and G49A (i.e. glycine to alanine). In conclusion, α-EPTX-Na1a is a potent, pseudo-irreversible, short-chain neurotoxin. The high prevalence of α-EPTX-Na1a in Chinese N. atra venom is likely to explain the mild neurotoxicity experienced by envenomed patients.]]> Tue 28 Nov 2023 12:09:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33132 Tue 28 Aug 2018 12:56:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36665 max = 91 ± 1%) in pre-contracted mesenteric arteries. In contrast, E. ocellatus venom (1 μg/ml) only produced a maximum relaxant effect of 27 ± 14%, suggesting that rapid cardiovascular collapse is unlikely to be due to peripheral vasodilation. The prevention of rapid cardiovascular collapse, by 'priming' doses of venom, supports a role for depletable endogenous mediators in this phenomenon.]]> Tue 23 Jun 2020 12:29:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43153 Tue 13 Sep 2022 15:28:50 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39247 Bungarus multicinctus, the Chinese krait, is a highly venomous elapid snake which causes considerable morbidity and mortality in southern China. B. multicinctus venom contains pre-synaptic PLA2 neurotoxins (i.e., β-bungarotoxins) and post-synaptic neurotoxins (i.e., α-bungarotoxins). We examined the in vitro neurotoxicity of B. multicinctus venom, and the efficacy of specific monovalent Chinese B. multicinctus antivenom, and Australian polyvalent elapid snake antivenom, against venom-induced neurotoxicity. B. multicinctus venom (1–10 μg/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic α-neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese B. multicinctus antivenom (12 U/mL) or Australian polyvalent snake antivenom (15 U/mL), markedly attenuated the neurotoxic actions of B. multicinctus venom (3 μg/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of B. multicinctus antivenom (60 U/mL), or Australian polyvalent snake antivenom (50 U/mL), at the t₉₀ time point after the addition of B. multicinctus venom (3 μg/mL), did not restore the twitch height over 180 min. The earlier addition of B. multicinctus antivenom (60 U/mL), at the t₂₀ or t₅₀ time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t₉₀ values. Repeated washing of the preparation with physiological salt solution, commencing at the t₂₀ time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that B. multicinctus venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by antivenom. This does not appear to be related to antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.]]> Thu 28 Jul 2022 14:45:09 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51188 Thu 24 Aug 2023 14:39:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51189 Thu 24 Aug 2023 14:38:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51185 Thu 24 Aug 2023 14:37:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44458 Naja) cause severe local dermonecrosis and myonecrosis, resulting in permanent disabilities. We studied the time scale in which two Indian polyvalent antivenoms, VINS and Bharat, remain capable of preventing or reversing in vitro myotoxicity induced by common cobra (Naja naja) venom from Sri Lanka using the chick biventer cervicis nerve-muscle preparation. VINS fully prevented while Bharat partially prevented (both in manufacturer recommended concentrations) the myotoxicity induced by Naja naja venom (10 μg/mL) when added to the organ baths before the venom. However, both antivenoms were unable to reverse the myotoxicity when added to organ baths 5 and 20 min post-venom. In contrast, physical removal of the venom from the organ baths by washing the preparation 5 and 20 min after the venom resulted in full and partial prevention of the myotoxicity, respectively, indicating the lag period for irreversible cellular injury. This suggests that, although the antivenoms contain antibodies against cytotoxins of the Sri Lankan Naja naja venom, they are either unable to reach the target sites as efficiently as the cytotoxins, unable to bind efficiently with the toxins at the target sites, or the binding with the toxins simply fails to prevent the toxin-target interactions.]]> Thu 13 Oct 2022 15:06:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8224 Sat 24 Mar 2018 08:40:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7354 Sat 24 Mar 2018 08:40:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14483 Sat 24 Mar 2018 08:25:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14560 Sat 24 Mar 2018 08:24:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14409 Sat 24 Mar 2018 08:24:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14463 25 kDa. All venoms (10 μg/ml) demonstrated in vitro neurotoxicity in the chick biventer cervicis nerve-muscle preparation, with a relative rank order of: H. signata ≥ D. devisi ≥ V. annulata = E. curta > C. boschmai. CSL polyvalent antivenom neutralized the inhibitory effects of C. boschmai venom but only delayed the inhibitory effect of the other venoms. All venoms displayed PLA2 activity but over a wide range (i.e. 1–621 μmol/min./mg). The venoms of C. boschmai (60 μg/kg, i.v.), D. devisi (60 μg/kg, i.v.) and H. signata (60 μg/kg, i.v.) produced hypotensive effects in vivo in an anaesthetized rat preparation. H. signata displayed moderate pro-coagulant activity while the other venoms were weakly pro-coagulant. This study demonstrated that these understudied Australian elapids have varying pharmacological activity, with notable in vitro neurotoxicity for four of the venoms, and may produce mild to moderate effects following systemic envenoming.]]> Sat 24 Mar 2018 08:19:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14476 Sat 24 Mar 2018 08:18:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14474 Sat 24 Mar 2018 08:18:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14479 Sat 24 Mar 2018 08:18:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14475 Sat 24 Mar 2018 08:18:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14480 Sat 24 Mar 2018 08:18:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14546 Sat 24 Mar 2018 08:18:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12441 50 values were determined. Results: Acanthophis spp. and Naja spp. venoms produced concentration-dependent inhibition of cell proliferation in both cell lines. Naja spp. venoms were significantly more cytotoxic than the most potent Acanthophis venom (i.e. A. antarcticus) in both cell lines. Naja spp. venoms also displayed higher sensitivity in L6 cells. SAIMR antivenom significantly inhibited the cytotoxic actions of all Naja spp. venoms in both A7r5 and L6 cells. However, death adder antivenom (CSL Ltd) was unable to negate the cytotoxic effects of Acanthophis spp. venoms. Discussion: Concentrations of the predominantly cytotoxic Naja spp. venoms used were approximately three times less than the predominantly neurotoxic Acanthophis spp. venoms. SAIMR antivenom was partially effective in neutralising the effects of Naja spp. venoms. Death adder antivenom(CSL Ltd) was not effective in negating the cytotoxic effects of venom from Acanthophis spp. These results indicate that the cell-based assay is suited to the examination of cytotoxic snake venoms and may be used in conjunction with organ bath experiments to pharmacologically characterise snake venoms. Furthermore, the results suggest that the use of a skeletalmuscle cell line is likely to bemore clinically relevant for the examination of cytotoxic snake venoms.]]> Sat 24 Mar 2018 08:17:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10648 Sat 24 Mar 2018 08:13:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10032 Sat 24 Mar 2018 08:12:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5331 Sat 24 Mar 2018 07:45:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28296 Pseudonaja spp.)-induced early cardiovascular collapse is a life-threatening medical emergency in Australia. We have previously shown that this effect can be mimicked in animals and is mediated via the release of endogenous mediators. In the present study, we aimed to purify and characterize the component in Pseudonaja textilis venom which induces cardiovascular collapse following envenoming. The component (fraction 3) was isolated using a combination of techniques including hydroxyapatite and reverse phase chromatography. Fraction 3 (10 or 20 µg/kg, i.v.) produced a rapid decrease in mean arterial pressure (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2 and 5 µg/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 µg/ml), but not fraction 3 (1 or 3 µg/ml), induced endothelium-dependent relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the presence of 9-10 protein bands of fraction 3. Using proteomic based analysis some protein bands of fraction 3 were identified as subunits of venom prothrombin activator, pseutarin C of P. textilis venom. Our results conclude that prothrombin activator-like toxin is likely to be a contributor to the rapid collapse induced by P. textilis venom.]]> Sat 24 Mar 2018 07:33:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50633 Mon 31 Jul 2023 15:59:57 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50978 Mon 14 Aug 2023 15:25:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28057 Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell’s vipers. This study aimed to investigate evidence of myotoxicity in Russell’s viper envenoming, response to antivenom and the toxins responsible for myotoxicity. Methodology and Findings: Clinical features of myotoxicity were assessed in authenticated Russell’s viper bite patients admitted to a Sri Lankan teaching hospital. Toxins were isolated using high-performance liquid chromatography. In-vitro myotoxicity of the venom and toxins was investigated in chick biventer nerve-muscle preparations. Of 245 enrolled patients, 177 (72.2%) had local myalgia and 173 (70.6%) had local muscle tenderness. Generalized myalgia and muscle tenderness were present in 35 (14.2%) and 29 (11.8%) patients, respectively. Thirty-seven patients had high (>300 U/l) serum creatine kinase (CK) concentrations in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). Peak venom and 24h CK concentrations were not associated (Spearman’s correlation; p = 0.48). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049). Venom caused concentration-dependent inhibition of direct twitches in the chick biventer cervicis nerve-muscle preparation, without completely abolishing direct twitches after 3 h even at 80 μg/ml. Indian polyvalent antivenom did not prevent in-vitro myotoxicity at recommended concentrations. Two phospholipase A2 toxins with molecular weights of 13kDa, U1-viperitoxin-Dr1a (19.2% of venom) and U1-viperitoxin-Dr1b (22.7% of venom), concentration dependently inhibited direct twitches in the chick biventer cervicis nerve-muscle preparation. At 3 μM, U1-viperitoxin-Dr1a abolished twitches, while U1-viperitoxin-Dr1b caused 70% inhibition of twitch force after 3h. Removal of both toxins from whole venom resulted in no in-vitro myotoxicity. Conclusion: The study shows that myotoxicity in Sri Lankan Russell’s viper envenoming is mild and non-life threatening, and due to two PLA2 toxins with weak myotoxic properties.]]> Mon 11 Mar 2019 12:11:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40416 Oxyuranus scutellatus) envenoming causes life-threatening neuromuscular paralysis in humans. We studied the time period during which antivenom remains effective in preventing and arresting in vitro neuromuscular block caused by taipan venom and taipoxin. Venom showed predominant pre-synaptic neurotoxicity at 3 µg/mL and post-synaptic neurotoxicity at 10 µg/mL. Pre-synaptic neurotoxicity was prevented by addition of Australian polyvalent antivenom before the venom and taipoxin and, reversed when antivenom was added 5 min after venom and taipoxin. Antivenom only partially reversed the neurotoxicity when added 15 min after venom and had no significant effect when added 30 min after venom. In contrast, post-synaptic activity was fully reversed when antivenom was added 30 min after venom. The effect of antivenom on pre-synaptic neuromuscular block was reproduced by washing the bath at similar time intervals for 3 µg/mL, but not for 10 µg/mL. We found an approximate 10–15 min time window in which antivenom can prevent pre-synaptic neuromuscular block. This time window is likely to be longer in envenomed patients due to the delay in venom absorption. Similar effectiveness of antivenom and washing with 3 µg/mL venom suggests that antivenom most likely acts by neutralizing pre-synaptic toxins before they interfere with neurotransmission inside the motor nerve terminals.]]> Mon 11 Jul 2022 14:44:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40389 Oxyuranus scutellatus from four localities on the north-east coast of Australia, spanning a distance of 2000 km. The intra-specific variation in taipan venom was considerably less than the inter-specific variation between it and the other Australian elapids to which it was compared. The electrophoretic venom profile of O. scutellatus was visually different to six other genera of Australian elapids, but not to its congener inland taipan O. microlepidotus. There was minimal geographical variation in taipan venom, as the intra-population variation exceeded the inter-population variation for enzymatic activity, procoagulant activity, and the abundance of neurotoxins. The pre-synaptic neurotoxin (taipoxin) was more abundant than the post-synaptic neurotoxins (3FTx), with a median of 11.0% (interquartile range (IQR): 9.7% to 18.3%; range: 6.7% to 23.6%) vs. a median of 3.4% (IQR: 0.4% to 6.7%; range: 0% to 8.1%). Three taipan individuals almost completely lacked post-synaptic neurotoxins, which was not associated with geography and occurred within two populations. We found no evidence of sexual dimorphism in taipan venom. Our study provides a basis for evaluating the significance of intra-specific venom variation within a phylogenetic context by comparing it to the inter-specific and inter-generic variation. The considerable intra-population variation we observed supports the use of several unpooled individuals from each population when making inter-specific comparisons.]]> Mon 11 Jul 2022 11:21:41 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30363 Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this.]]> Fri 18 Sep 2020 15:18:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25369 Bungarus caeruleus and Bungarus fasciatus venoms was neutralised by all antivenoms except TCAV, which did not neutralise pre-synaptic activity. Post-synaptic neurotoxicity of Ophiophagus hannah was neutralised by all antivenoms, and Naja kaouthia by all antivenoms except IPAV. Pre- and post-synaptic neurotoxicity of Notechis scutatus was neutralised by all antivenoms, except TCAV, which only partially neutralised pre-synaptic activity. Pre- and post-synaptic neurotoxicity of Oxyuranus scutellatus was neutralised by TNPAV and APAV, but TCAV and IPAV only neutralised post-synaptic neurotoxicity. Post-synaptic neurotoxicity of Acanthophis antarcticus was neutralised by all antivenoms except IPAV. Pseudonaja textillis post-synaptic neurotoxicity was only neutralised by APAV. The a-neurotoxins were neutralised by TNPAV and APAV, and taipoxin by all antivenoms except IPAV. Antivenoms raised against venoms with post-synaptic neurotoxic activity (TCAV) cross-neutralised the post-synaptic activity of multiple snake venoms. Antivenoms raised against pre- and post-synaptic neurotoxic venoms (TNPAV, IPAV, APAV) cross-neutralised both activities of Asian and Australian venoms. While acknowledging the limitations of adding antivenom prior to venom in an in vitro preparation, cross-neutralization of neurotoxicity means that antivenoms from one region may be effective in other regions which do not have effective antivenoms. TCAV only neutralized post-synaptic neurotoxicity and is potentially useful in distinguishing pre-synaptic and post-synaptic effects in the chick biventer cervicis preparation.]]> Fri 18 Sep 2020 15:17:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22947 Fri 13 Jul 2018 15:45:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51342 Fri 01 Sep 2023 13:34:38 AEST ]]>