The same phenomenon can be observed turbidimetrically MDV3100 in vivo in solution which has been shown for venoms
and antivenoms (O’Leary, Maduwage et al., 2013). In the measurement of VAV, the maximum signal or VAV peak occurs when there is on average V(AV)n − 1 in the antivenom/venom mixture, which means that each venom molecule is attached to at least one antivenom molecule (antibody). This can then be used as a marker of efficacy because it means that all venom molecules (toxins) are bound to at least one antibody, so they cannot distribute to their site of action and/or can be eliminated. This antivenom:venom ratio measured over a range of venom concentrations as a slope appears to be constant (Fig. 5). Table 1 gives results obtained for some Australian snake venoms with the commercial antivenoms. Interestingly, these values of between 0.4 and 1.7 U required for 10 μg of venom, compare to the original definition from manufacturer of antivenom activity Alectinib cell line as 1 U being sufficient to neutralise 10 μg of venom (Sutherland and Tibballs, 2001). While “neutralise” is not defined, it can be argued that the attachment of at least one antivenom
molecule (antibody) to a venom molecule, even if not near the active site of the molecule, is sufficient to prevent it from leaving the circulation and render it susceptible to removal by the reticulo-endothelial system or by circulating phagocytes. In this study we have only shown the detection of VAV in in vitro mixtures of venom
and Tacrolimus (FK506) antivenom. A more useful application of this assay would be to measure VAV in patients’ sera after the administration of antivenom, particularly in cases where there remains detectable venom using the free venom assay or in cases where there is venom recurrence. In the former the VAV assay may show that detectable venom is in fact all VAV, so that all of the venom molecules in vivo are bound to at least one antivenom molecule. In the case of purported venom recurrence the VAV assay may also show that there is only bound venom present (i.e. VAV), so there is not true venom recurrence. The VAV assay will therefore provide a useful tool for the investigation of free and bound venom in envenomed patients. “
“Envenomation caused by Crotalus snake bites represents 6.2% of reported cases of envenomation in Brazil, with an estimated mortality rate of 1.8% per year ( Ministério da Saúde, Brasil, 2001). As is shown in Fig. 1, five geographic subspecies of Crotalus are found in Brazil. Crotalus durissus terrificus, although common in the southern states of São Paulo, Minas Gerais, Paraná and Rio Grande do Sul, is also present in the areas of Mato Grosso, Rondônia, Amazonas and Pará to the west, including Paraguai, Uruguai and Argentina.