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We present a case of severe taipan envenoming in northern New South Wales in a 68-year-old man. He developed severe neurotoxicity requiring intubation and ventilation, venom-induced consumption coagulopathy, myotoxicity and thrombotic microangiopathy with acute kidney injury requiring dialysis. He was administered brown and tiger snake antivenom consistent with guidelines and snake occurrence in the region. Taipan venom was detected in serum (72 ng/ml) following concern about the severity of neurotoxicity, clinical toxicology consultation and a concurrent report of a taipan in the area. Based on this it would be prudent to stock and consider treating with polyvalent antivenom in north-eastern New South Wales and south-eastern Queensland. [ABSTRACT FROM AUTHOR]

Kashmir has a special status under Article 370 and 35A of the Indian Constitution, which granted special autonomy of Kashmir. The paper examines the reasons behind the Indian government's policy under Indian Prime Minister Narendra Modi to revoke the special status of Kashmir. The question is, why the Indian government revoked the special status of Kashmir in 2019 when the special status has been entrenched in the last 73 years ago. The objective of this research is to identify the reasons behind the Indian government's policy to revoke the special status of Kashmir. By a qualitative research, the findings show that the existence of economic interests is the background for revoking the special status of Kashmir. The research argues that the Indian business group (Taipan) as a major milestone in the success of Narendra Modi campaigns in 2014 and 2019 elections, demanding the Indian government to eliminate regulatory barriers between the center and the regions, to create a national market without any restrictions. Demands given by Taipan cause the dynamics between the central and local governments. This research is expected to assist the development of international relations in political economy studies.

The phospholipase A 2 (PLA 2) inhibitors varespladib (LY315920) and its orally available derivative methyl-varespladib (LY333013) have been proposed as potential therapies for the treatment of snakebite envenomings in which toxicity depends on the action of PLA 2 s. In this study, the ability of LY315920 to abrogate the effect of the potent neurotoxic venom of Oxyuranus scutellatus (taipan) was assessed using the mouse phrenic nerve-diaphragm preparation. LY315920 inhibited the venom when (a) incubated with venom before addition to the medium; (b) added to the medium before addition of venom, and; (c) added to the medium within 30 min after addition of venom, and even after the onset of decline in twitch response. This contrasts with previous results with antivenom using the same experimental model, in which the window of time when antibodies are effective is shorter than 10 min. It is proposed that such differences may depend either on the higher affinity of the inhibitor for PLA 2 s or on the possibility that LY315920 reaches the cytosol of the nerve terminals, inhibiting neurotoxins that have been internalized. Our findings bear implications on the therapeutic potential of varespladib in neurotoxic snakebite envenomings mediated by presynaptically-acting PLA 2 s. • Oxyuranus scutellatus venom inhibits neuromuscular transmission ex vivo. • Varespladib inhibits the neuromuscular blocking effect of Oxyuranus scutellatus venom. • Varespladib halts the neuromuscular blockade when added after venom. • Varespladib is effective at halting the blockage at times when antivenom is ineffective. [ABSTRACT FROM AUTHOR]

Coastal taipan (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.

Intra-specific venom variation has the potential to provide important insights into the evolution of snake venom, but remains a relatively neglected aspect of snake venom studies. We investigated the venom from 13 individual coastal taipans 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.

A previously well man developed acute, marked tender bilateral gynaecomastia two months after confirmed taipan (Oxyuranus scutellatus) envenomation. He had had laboratory evidence of thrombotic microangiopathy (TMA) including microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury. Scrotal ultrasound revealed bilateral testicular atrophy, his serum testosterone was repeatedly low, while his luteinising and follicle stimulating hormone were elevated. It is hypothesised that TMA-related testicular ischaemia was responsible for his primary gonadal failure and dramatic clinical presentation. • Taipan envenomation is uncommon, and its complications are incompletely defined. • Reports of endocrine complications after snakebites are infrequent. • Thrombotic microangiopathy can occur with taipan envenomation. • Thrombotic microangiopathy classically affects the kidneys but can affect any organ. • TMA-related end-organ injury may result in delayed clinical presentations. [ABSTRACT FROM AUTHOR]

Taipans are highly venomous Australo-Papuan elapids. A new species of taipan, the Western Desert Taipan (Oxyuranus temporalis), has been discovered with two specimens housed in captivity at the Adelaide Zoo. This study is the first investigation of O. temporalis venom and seeks to characterise and compare the neurotoxicity, lethality and biochemical properties of O. temporalis venom with other taipan venoms. Analysis of O. temporalis venom using size-exclusion and reverse-phase HPLC indicated a markedly simplified “profile” compared to other taipan venoms. SDS-PAGE and agarose gel electrophoresis analysis also indicated a relatively simple composition. Murine LD50 studies showed that O. temporalis venom is less lethal than O. microlepidotus venom. Venoms were tested in vitro, using the chick biventer cervicis nerve-muscle preparation. Based on t90 values, O. temporalis venom is highly neurotoxic abolishing indirect twitches far more rapidly than other taipan venoms. O. temporalis venom also abolished responses to exogenous acetylcholine and carbachol, indicating the presence of postsynaptic neurotoxins. Prior administration of CSL Taipan antivenom (CSL Limited) neutralised the inhibitory effects of all taipan venoms. The results of this study suggest that the venom of the O. temporalis is highly neurotoxic in vitro and may contain procoagulant toxins, making this snake potentially dangerous to humans.

Envenomation by hemotoxic enzymes continues to be a major cause of morbidity and mortality throughout the world. With regard to treatment, the gold standard to abrogate coagulopathy caused by these venoms is still the administration of antivenom; however, despite antivenom therapy, coagulopathy still occurs and recurs. Of interest, this laboratory has demonstrated in vitro and in vivo that coagulopathy inducing venom derived from snakes of the family Viperidae exposed to carbon monoxide (CO) is inhibited, potentially by an attached heme. The present investigation sought to determine if venoms derived from snakes of the Elapidae family (taipans and cobras) could also be inhibited with CO or with the metheme inducing agent, O-phenylhydroxylamine (PHA). Assessing changes in coagulation kinetics of human plasma with thrombelastography, venoms from Elapidae snakes were exposed in isolation to CO (five species) or PHA (one specie) and placed in human plasma to assess changes in procoagulant or anticoagulant activity. The procoagulant activity of two taipan venoms and anticoagulant activity of three cobra venoms were significantly inhibited by CO. The venom of the inland taipan was also inhibited by PHA. In sum, these data demonstrate indirectly that the biometal heme is likely bound to these disparate venoms as an intermediary modulatory molecule. In conclusion, CO may not just be a potential therapeutic agent to treat envenomation but also may be a potential modulator of heme as a protective mechanism for venomous snakes against injury from their own proteolytic venoms. [ABSTRACT FROM AUTHOR]

Alpaca ( Vicugna pacos ), like all other members of the camelid family, produce a unique heavy chain only IgG subclass. This form of IgG has been proposed as having superior neutralising properties and improved safety as compared with conventional mammalian IgG-based immunotherapeutics. The objective of this study was to investigate the potential of alpaca antibodies to neutralise the lethal and procoagulant properties of several Australian elapid snake venoms. Various experimental antivenoms were produced by immunisation of alpaca ( Vicugna pacos ) with combinations of five Australian elapid snake venoms: tiger snake ( Notechis scutatus ), eastern brown snake ( Pseudonaja textilis ), Papuan taipan ( Oxyuranus scutellatus canni ), mulga snake ( Pseudechis australis ) and common death adder ( Acanthophis antarcticus ). Venoms were emulsified in Freund’s Incomplete Adjuvant and alpaca repeatedly immunised. Having previously shown that such alpaca produce persistent venom-specific antibody responses with minimal physiological impact on the animal, the current report demonstrates that polyvalent alpaca antivenom neutralises the lethal effects of three elapid venoms (tiger, brown and Papuan taipan venoms). Such lethality neutralisation was, however, of generally lower potency, but of the same order of magnitude, when compared with bioCSL monovalent antivenoms (brown, tiger and taipan antivenoms). By contrast, the monovalent alpaca tiger and brown snake antivenom were found to be superior to the equivalent bioCSL monovalent antivenoms when considering the neutralisation of the procoagulant effects of the respective immunising venoms. The bioCSL polyvalent antivenom also less potent, when compared with the alpaca taipan monovalent antivenom, against Papuan taipan venom procoagulant neutralisation. These findings support the potential of camelid immunoglobulin for the development of novel elapid specific antivenoms. [ABSTRACT FROM AUTHOR]

There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.

Context:Taipans (Oxyuranusspp.) are medically important venomous snakes from Australia and Papua New Guinea. The objective of this study was to describe taipan envenoming in Australian and its response to antivenom. Methods:Confirmed taipan bites were recruited from the Australian Snakebite Project. Data were collected prospectively on all snakebites, including patient demographics, bite circumstances, clinical effects, laboratory results, complications and treatment. Blood samples were taken and analysed by venom specific immunoassay to confirm snake species and measure venom concentration pre- and post-antivenom. Results:There were 40 confirmed taipan bites: median age 41 years (2–85 years), 34 were males and 21 were snake handlers. Systemic envenoming occurred in 33 patients with neurotoxicity (26), complete venom induced consumption coagulopathy (VICC) (16), partial VICC (15), acute kidney injury (13), myotoxicity (11) and thrombocytopenia (7). Venom allergy occurred in seven patients, three of which had no evidence of envenoming and one died. Antivenom was given to 34 patients with a median initial dose of one vial (range 1–4), and a median total dose of two vials (range 1–9). A greater total antivenom dose was associated with VICC, neurotoxicity and acute kidney injury. Early antivenom administration was associated with a decreased frequency of neurotoxicity, acute kidney injury, myotoxicity and intubation. There was a shorter median time to discharge of 51 h (19–432 h) in patients given antivenom <4 h post-bite, compared to 175 h (27–1104 h) in those given antivenom >4 h. Median peak venom concentration in 25 patients with systemic envenoming and a sample available was 8.4 ng/L (1–3212 ng/L). No venom was detected in post-antivenom samples, including 20 patients given one vial initially and five patients bitten by inland taipans. Discussion:Australian taipan envenoming is characterised by neurotoxicity, myotoxicity, coagulopathy, acute kidney injury and thrombocytopenia. One vial of antivenom binds all measurable venom and early antivenom was associated with a favourable outcome. [ABSTRACT FROM PUBLISHER]

Alpaca ( Vicugna pacos ) are domesticated members of the camelid family that have been shown to produce an IgG subclass that is heavy chain only IgG. This camelid-type IgG has been postulated to have improved neutralising properties and reduced immunogenicity, compared with conventional mammalian IgG. This study was undertaken to describe the physiological and antibody responses of alpaca ( Vicugna pacos ) used for the production of an experimental camelid antivenom. Various antivenom products were developed by immunisation of alpaca with combinations of five Australian elapid snake venoms: common tiger snake ( Notechis scutatus ), eastern brown snake ( Pseudonaja textilis ), Papuan taipan ( Oxyuranus scutellatus canni ), mulga snake ( Pseudechis australis ) and common death adder ( Acanthophis antarcticus ) were emulsified with Freund’s Adjuvant and injected monthly using a low dose multi-site approach. Venom specific immune responses were monitored by ELISA. Physiological effects upon alpaca were monitored by clinical examination combined with serial haematology and biochemical profiles. Serum was harvested once immune responses had peaked and the IgG fraction concentrated by ammonium sulphate precipitate of non-IgG proteins. Total serum IgG and total serum protein concentrations increased and decreased in synchrony with boosting specific antibodies. The difference in serum creatinine kinase concentration measured at 24 h after each of the first three immunisations decreased as the alpaca mounted an antibody response to the venom antigens measured by ELISA. In conclusion, alpaca responded to repeated immunisation with various Australian elapid venoms by mounting an increasing antibody response that persisted following prolonged rest with minimal physiological impact on the animal. [ABSTRACT FROM AUTHOR]

This paper makes an original contribution to human–animal studies through the application of social construction theory to an iconic species of Australian snake, the coastal taipan. Little research attention using this approach has been focused on reptiles, and this study addresses this gap in the literature. The taipan has achieved a high level of notoriety in Australia. This paper seeks to understand why and how this has occurred. Drawing on a range of data derived from analysis of newspaper articles, popular magazines and books, and the scientific literature, four dominant narratives are identified: the taipan as an object of science and natural history, as social problem, as object quest and as celebrity. The insights gained from this study support the contention that the meanings made of Australia's fauna are fluid, historically contextualised and socially constructed. In the specific case of the taipan, key individuals, including scientists, popular natural historians and snake men contributed greatly to the species’ construction, as did popular cultural forms such as newspapers and natural history books. [ABSTRACT FROM AUTHOR]

Case report An 8-year-old mixed-breed dog was envenomed by a juvenile coastal taipan ( Oxyuranus scutellatus). The dog presented initially with coagulopathy and weakness, then developed neuromuscular paralysis and respiratory failure. Progressive myopathy peaked 3 days following admission. Taipan antivenom administration, mechanical ventilation therapy and supportive patient care resulted in complete recovery. Symptoms of neuropathy began to resolve 3 days following envenomation, with the dog discharged 6 days following envenomation. Conclusion To the author's knowledge, this is the first reported case of coastal taipan envenomation of a dog. [ABSTRACT FROM AUTHOR]

Taipans are highly venomous Australo-Papuan elapids. A new species of taipan, the Western Desert Taipan (Oxyuranus temporalis), has been discovered with two specimens housed in captivity at the Adelaide Zoo. This study is the first investigation of O. temporalis venom and seeks to characterise and compare the neurotoxicity, lethality and biochemical properties of O. temporalis venom with other taipan venoms. Analysis of O. temporalis venom using size-exclusion and reverse-phase HPLC indicated a markedly simplified "profile" compared to other taipan venoms. SDS-PAGE and agarose gel electrophoresis analysis also indicated a relatively simple composition. Murine LD50 studies showed that O. temporalis venom is less lethal than O. microlepidotus venom. Venoms were tested in vitro, using the chick biventer cervicis nerve-muscle preparation. Based on t90 values, O. temporalis venom is highly neurotoxic abolishing indirect twitches far more rapidly than other taipan venoms. O. temporalis venom also abolished responses to exogenous acetylcholine and carbachol, indicating the presence of postsynaptic Oxyuranus temporalis; taipan; antivenom; neurotoxicity; snake; venomneurotoxins. Prior administration of CSL Taipan antivenom (CSL Limited) neutralised the inhibitory effects of all taipan venoms. The results of this study suggest that the venom of the O. temporalis is highly neurotoxic in vitro and may contain procoagulant toxins, making this snake potentially dangerous to humans. [ABSTRACT FROM AUTHOR]

Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of taipans exist, and the venom from each species contains a presynaptic neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic neurotoxins in taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve-muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment ( P < 0.0001). However, paradoxin induced a 32 % decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone ( P < 0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following taipan envenoming. [ABSTRACT FROM AUTHOR]

Abstract: The venom proteomes of populations of the highly venomous taipan snake, Oxyuranus scutellatus, from Australia and Papua New Guinea (PNG), were characterized by reverse-phase HPLC fractionation, followed by analysis of chromatographic fractions by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. Proteins belonging to the following seven protein families were identified in the two venoms: phospholipase A2 (PLA2), Kunitz-type inhibitor, metalloproteinase (SVMP), three-finger toxin (3FTx), serine proteinase, cysteine-rich secretory proteins (CRISP), and coagulation factor V-like protein. In addition, C-type lectin/lectin-like protein and venom natriuretic peptide were identified in the venom of specimens from PNG. PLA2s comprised more than 65% of the venoms of these two populations. Antivenoms generated against the venoms of these populations showed a pattern of cross-neutralization, corroborating the immunological kinship of these venoms. Toxicity experiments performed in mice suggest that, at low venom doses, neurotoxicity leading to respiratory paralysis represents the predominant mechanism of prey immobilization and death. However, at high doses, such as those injected in natural bites, intravascular thrombosis due to the action of the prothrombin activator may constitute a potent and very rapid mechanism for killing prey. [Copyright &y& Elsevier]

Abstract: Based on murine LD50 values, the taipans (i.e. Oxyuranus microlepidotus, Oxyuranus scutellatus and Oxyuranus scutellatus canni) are the most venomous snake genus in the world. Despite this, little is known about the toxins contained in their venoms. The aim of the present study was to isolate and characterise post-synaptic neurotoxins from the venoms of the Papuan taipan (O. s. canni) and coastal taipan (O. scutellatus), and to compare their pharmacology. A 6770Da toxin (i.e. α-oxytoxin 1) and a 6781Da toxin (i.e. α-scutoxin 1) were isolated from the venoms of O. s. canni and O. scutellatus, respectively, using reverse-phase high performance liquid chromatography. Both α-oxytoxin 1 (0.3–1μM) and α-scutoxin 1 (0.1–1μM) caused concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve-muscle preparation. Contractile responses to exogenous carbachol (CCh), but not potassium chloride (KCl), were inhibited by both toxins, suggesting a post-synaptic mode of action. The inhibitory effect of α-oxytoxin 1 was reversed by washing. Cumulative concentration–response curves to CCh were obtained in the presence and absence of the toxins with the subsequently determined pA2 of α-scutoxin 1 being 44.7-fold higher than α-oxytoxin 1 (i.e. 8.38±0.59 versus 7.62±0.04). The current study shows that Papuan taipan and coastal taipan venom both contain potent post-synaptic neurotoxins which exhibit different pharmacological profiles. The effect of α-oxytoxin 1 is atypical of most snake venom post-synaptic neurotoxins displaying a ‘competitive’ mode of action, whereas α-scutoxin 1 possesses pseudo-irreversible or non-competitive activity. [Copyright &y& Elsevier]

Abstract: Many snake venoms contain procoagulant toxins that activate the coagulation cascade and cause venom-induced consumptive coagulopathy (VICC). We developed a semi-mechanistic model of the clotting cascade in order to explore the effects of the procoagulant toxin from taipan venom on this system as well as the effects of antivenom. Simulations of the time course in the change of clotting factors were compared to data collected from taipan envenomed patients. The model accurately predicted the observed concentration of clotting factors over time following taipan envenomation. Investigations from the model indicated that the upper limit of the half-life of the procoagulant toxin was 1h. Simulations from the model also suggest that antivenom for Australasian elapids has negligible effect on reducing the recovery time of the coagulation profile unless administered almost immediately after envenomation. The model has generality to be expanded to describe the effects of other venoms and drugs on the clotting cascade. [Copyright &y& Elsevier]

Inelastic neutron scattering is a widely used technique to study phonon and magnon excitations in condensed matter and the triple axis spectrometer (TAS) is one of the main instruments used for such inelastic neutron scattering studies. As a consequence the TAIPAN TAS will be the first inelastic instrument at the new Australian research reactor OPAL. It will be located on a thermal neutron beam tube at the reactor shielding face and can be operated either in a high flux mode, with a double focusing monochromator and analyser, or in a traditional mode of operation with Soller collimators providing high resolution. A polarisation analysis capability will be realised on TAIPAN using supermirror benders. [ABSTRACT FROM AUTHOR]

To describe the epidemiology, clinical features, treatment and outcomes of patients with elapid snake envenoming in far north Queensland. Review of patients admitted with snake envenoming to Cairns Base Hospital, Queensland, from 1 January 1996–31 December 2000. A total of 264 patients presented to the hospital with a diagnosis of snakebite. Of these, 27 (10%) had clinical evidence of envenoming, including seven children. All envenomed patients had been bitten on a limb. Two patients had correct initial first aid applied. Commercially available venom detection kits were used in 23 patients; 14 (61%) bite site swabs were positive, but only four (23%) of 17 urine Venom Detection Kits were positive. Antivenom was administered to 20 envenomed patients. The five brown snake envenomed patients required a median of 9 ampoules of antivenom to treat their coagulopathy. Sixteen patients were admitted to the ICU, with six requiring ventilation. Six patients were successfully managed in the ED observation ward. Three patients envenomed by a taipan, and one by a death adder were discharged with ongoing neurological symptoms. There was one death from brown snake envenoming. The incidence of snakebite and envenoming in far north Queensland is higher than reported from hospitals in capital cities and is a significant health issue. [ABSTRACT FROM AUTHOR]

Coastal taipan (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. [ABSTRACT FROM AUTHOR]

Intra-specific venom variation has the potential to provide important insights into the evolution of snake venom, but remains a relatively neglected aspect of snake venom studies. We investigated the venom from 13 individual coastal taipans 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. [ABSTRACT FROM AUTHOR]

There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts. [ABSTRACT FROM AUTHOR]