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RBCs (red blood cells) circulating through narrow blood capillaries withstand major deformation. The mechanical and chemical stresses commonly exerted on RBCs continue to attract interest for the study of membrane structure and function. Snake venoms are lethal biochemical 'cocktails' that often contain haemotoxins, metalloproteinases, myotoxins, neurotoxins, phosphodiesterases, phospholipases and proteases. We have monitored the effects of 4 snake venoms ( Pseudechis guttatus, Oxyuranus scutellatus, Notechis scutatus and Naja kaouthia) on human RBCs using NMR spectroscopy, DIC (differential interference contrast) and confocal light microscopy. RBCs underwent reproducible stomatocytosis, with unusual geographical-like indentations, spherocytosis, followed by rapid lysis. Confocal micrographs using a fluorescent dye linked to phalloidin showed that the change in morphology was associated with the aggregation of actin in the cytoskeleton. 31P NMR saturation transfer experiments recorded transport of the univalent anion HPA (hypophosphite) on a subsecond time scale, thereby reporting on the function of capnophorin or Band 3 linked to the cytoskeleton; anion-exchange activity was substantially reduced by venom treatment. We propose a molecular-cytological hypothesis for the shape and functional changes that is different from, or supplementary to, the more 'traditional' bilayer-couple hypothesis more often used to account for similar morphological changes invoked by other reagents. [ABSTRACT FROM AUTHOR]

The article discusses developments in high-throughput screening of snake venoms indicating its contributions to clinical medicine as well as medical research. Medicinal use of snake venom is noted such as its use as defibrogenerating agent for several clinical conditions like deep vein thrombosis, myocardial infarction and pulmonary embolus. The article emphasizes the challenge is in the conservation of snake biodiversity, which is the basis where the development of new therapeutic agents from snake venom depends.

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]