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Snake venoms are recognized here as a grossly under-explored resource in pharmacological prospecting. Discoveries in snake systematics demonstrate that former taxonomic bias in research has led to the neglect of thousands of species of potential medical use. Recent discoveries reveal an unexpectedly vast degree of variation in venom composition among snakes, from different species down to litter mates. The molecular mechanisms underlying this diversity are only beginning to be understood. However, the enormous potential that this resource represents for pharmacological prospecting is clear. New high-throughput screening systems offer greatly increased speed and efficiency in identifying and extracting therapeutically useful molecules. At the same time a global biodiversity crisis is threatening the very snake populations on which hopes for new venom-derived medications depend. Biomedical researchers, pharmacologists, clinicians, herpetologists, and conservation biologists must combine their efforts if the full potential of snake venom-derived medications is to be realized., (Copyright © 2011 WILEY Periodicals, Inc.)

Many advanced snakes use fangs-specialized teeth associated with a venom gland-to introduce venom into prey or attacker. Various front- and rear-fanged groups are recognized, according to whether their fangs are positioned anterior (for example cobras and vipers) or posterior (for example grass snakes) in the upper jaw. A fundamental controversy in snake evolution is whether or not front and rear fangs share the same evolutionary and developmental origin. Resolving this controversy could identify a major evolutionary transition underlying the massive radiation of advanced snakes, and the associated developmental events. Here we examine this issue by visualizing the tooth-forming epithelium in the upper jaw of 96 snake embryos, covering eight species. We use the sonic hedgehog gene as a marker, and three-dimensionally reconstruct the development in 41 of the embryos. We show that front fangs develop from the posterior end of the upper jaw, and are strikingly similar in morphogenesis to rear fangs. This is consistent with their being homologous. In front-fanged snakes, the anterior part of the upper jaw lacks sonic hedgehog expression, and ontogenetic allometry displaces the fang from its posterior developmental origin to its adult front position-consistent with an ancestral posterior position of the front fang. In rear-fanged snakes, the fangs develop from an independent posterior dental lamina and retain their posterior position. In light of our findings, we put forward a new model for the evolution of snake fangs: a posterior subregion of the tooth-forming epithelium became developmentally uncoupled from the remaining dentition, which allowed the posterior teeth to evolve independently and in close association with the venom gland, becoming highly modified in different lineages. This developmental event could have facilitated the massive radiation of advanced snakes in the Cenozoic era, resulting in the spectacular diversity of snakes seen today.

Several snake venoms contain proteinases that activate zymogens in the coagulation cascade and thus exhibit their procoagulant effects. While most procoagulant proteinases from snake venoms are dissimilar to coagulation factors, Group D (trocarin, notecarin) and C (pseutarin) prothrombin activators are structural and functional homologues of factor Xa and the prothrombinase complex, respectively. We examined the effect of these and other procoagulants from snake venoms as well as mammalian and snake thromboplastins on the coagulation of plasmas of Notechis scutatus, Pseudonaja textilis (both procoagulant venoms), Python reticulatus (non-venomous) and Crotalus atrox (non-procoagulant venom) snakes. The results indicate that the intrinsic pathway seems to be weak or absent only in venomous snakes, while the extrinsic pathway is fully functional in all snakes. Python and Crotalus plasmas have extrinsic pathways similar to that in mammals. In contrast, although Notechis and Pseudonaja plasmas were clotted by a Group C activator, they failed to clot upon the addition of factor Xa and Group D activators. The mechanism of this resistance is still elusive.

The wet and dry venom yields for most Australian native dangerous snakes and a number of non-Australian species are presented. Snakes from the Pseudonaja genus yielded higher than previously published amounts and suggest reconsideration be given to increasing the volume of antivenom in each vial. Higher percentage solids were obtained from venoms from the 4 cobra species (Naja) and Pseudechis genus included in this series. [ABSTRACT FROM AUTHOR]

Brown snakes, Pseudonaja genus, cause more bites and deaths to animals and humans in Australia than any other terrestrial snake genus. Some aspects of treatment of brown snakebites with antivenom remain poorly managed due to the apparent inability of the antivenom to counter the prothrombin activator in the venom. We present evidence of a new novel antivenom (Antiven Pty Ltd Brown snake antivenom (ABSAV)), which shows high efficacy in reversing the hemostatic abnormality caused by brown snake envenomation. It is also more efficient at reversing overall toxicity. In clotting tests, it is substantially more potent than Commonwealth Serum Laboratories Ltd (CSL) Brown snake antivenom and is twice as effective in reversing overall toxicity than CSL Brown snake antivenom. Antiven Pty. Ltd. Brown snake antivenom is currently being assessed by the National Registration Authority (veterinary regulative body in Australia). [ABSTRACT FROM AUTHOR]

Keywords: Antivenoms; Bites and stings; Snake bites EN Antivenoms Bites and stings Snake bites 46 46 1 07/07/20 20200701 NES 200701 I B In reply b i I B : b i We note incorrect assertions in the comments by Isbister and colleagues regarding our article on single vial antivenom recommendations for elapid envenoming in Australia.[1] They state that we assigned the single dose recommendation solely to the study conducted by Johnston and colleagues.[2] However, we specifically indicated that this study was a summarised presentation of a longitudinal study - the Australian Snakebite Project - that "concluded that one vial of antivenom was sufficient to effectively treat envenoming by all taxa of Australian elapids".[1] Isbister and colleagues cite the Australian Snakebite Project as their sole evidence base, although evidence-based medical practice is based on a triad of evidence, of which clinical trials or other formal clinical research represent only one-third.[3] They also object to our criticisms about applying in vitro venom measurements using enzyme-linked immunosorbent assay (ELISA) and cited the in vitro measurement of venom-antivenom complexes to support their claim that a single vial of antivenom provides a concentration "at which every venom molecule is bound to at least one antivenom molecule". While the former minimises the antivenom volume, and the latter is to some extent true, the manufacturer still recommends provision of the correct antivenom for a given species of Australian elapid, as do we. [Extracted from the article]

Antivenom dosage for Australian elapid envenoming should be decided by clinical evaluation of individual patients Medically important venom components may proportionally vary, and some venom components may act synergistically, or/and antagonistically.[2] For example, some insular tiger snake ( I Notechis scutatus i ) populations (eg, on Chappell Island and Kangaroo Island) and some mainland specimens can produce venom volumes far greater than average reported yields. This was recognised by the antivenom manufacturer that recommended initial multiple vial antivenom doses for serious envenoming by snakes from insular populations.[[2], [9], [14]] Even some envenoming by Australian elapid species (eg, red-bellied black snake [ I Pseudechis porphyriacus i ]) that most authorities accept can be treated with a single vial of antivenom may sometimes require greater amounts of antivenom in order to effectively treat the seriously envenomed patient.[15]. [Extracted from the article]