Acute renal failure (ARF) is the most frequent and a serious complication in victims of Russell’s viper snakebites. Russell’s viper venom-factor X activator (RVV-X) has been identified as a main procoagulant enzyme involving coagulopathy, which might be responsible for changes in renal hemodynamics and renal functions. Here, we purified RVV-X from crude Russell’s viper venom to study renal hemodynamics, renal functions, intravascular clot, and histopathological changes in Sprague–Dawley rats. Changes in renal hemodynamics and renal functions were evaluated by measuring the mean arterial pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), renal vascular resistance (RVR), and fractional excretion of electrolytes. After 10 min, rats receiving both crude venom and purified RVV-X decreased GFR, ERPF, and ERBF and increased RVR. These changes correlated to renal lesions. Along with the determination of intravascular clot, rats injected with purified RVV-X increased the average D-dimer level and reached a peak at 10 min, declined temporarily, and then reached another peak at 30 min. The temporal association between clots and renal dysfunction was observed in rats within 10 min after the injection of purified RVV-X. These findings suggested RVV-X as a major cause of renal failure through intravascular clotting in the renal microcirculation.

Gnathostoma spinigerum infection is endemic in Thailand and many Asian countries. Current diagnosis is the skin test and enzyme-linked immunosorbent assay (ELISA) for IgG antibody against the G. spinigerum third-stage larvae (L3), but cross-reactivity is common. We evaluated the sensitivity and specificity of anti-G. spinigerum L3 IgG subclass antibodies for diagnosis of 43 patients with gnathostomiasis. The majority of patients with gnathostomiasis (91%) had eosinophilia. While the anti-G. spinigerum L3 IgG1 antibody provided the highest sensitivity (98%), the anti-G. spinigerum L3 IgG2 antibody had the highest specificity (88%). The ELISA that detected anti-G. spinigerum L3 IgG1 antibody could be a reliable laboratory screening test, while anti-G. spinigerum L3 IgG2 antibody could be used to confirm the diagnosis.

A novel snake venom cysteine-rich secretory protein (svCRiSP), Hellerin, was purified from C. o. helleri venom using sequential reverse phase and cation-exchange chromatography. Gel electrophoresis, N-terminal sequencing, and LC-MS/MS sequencing identified a single protein with a molecular mass of approximately 24.8 kDa and confirmed its identity as a svCRiSP. Hellerin had cytotoxic effects on human umbilical vein endothelial cells (HUVECs) in a dosedependent manner but not in human dermal lymphatic endothelial cells (HDLECs) and human dermal blood endothelial cells (HDBECs). Hellerin produced a dramatic increase in both blood vascular permeability in vivo, and in the trans-epithelial permeability of cultured HDLEC and HDBEC cells. This is the first study that describes the effect of a svCRiSP on vascular, blood and lymphatic permeability.

Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5–6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms.

Phenotypes frequently vary across and within species. The connection between specific phenotypic effects and function, however, is less understood despite being essential to our understanding of the adaptive process. Snake venoms are ideal for identifying functionally important phenotypic variation because venom variation is common, and venoms can be functionally characterized through simple assays and toxicity measurements. Previous work with the eastern diamondback rattlesnake (Crotalus adamanteus) used multivariate statistical approaches to identify six unique venom phenotypes. We functionally characterized hemolytic, gelatinase, fibrinogenolytic, and coagulant activity for all six phenotypes, as well as one additional venom, to determine if the statistically significant differences in toxin expression levels previously documented corresponded to differences in venom activity. In general, statistical differences in toxin expression predicted the identified functional differences, or lack thereof, in toxic activity, demonstrating that the statistical approach used to characterize C. adamanteus venoms was a fair representation of biologically meaningful differences. Minor differences in activity not accounted for by the statistical model may be the result of amino-acid differences and/or post-translational modifications, but overall we were able to link variation in protein expression levels to variation in function as predicted by multivariate statistical approaches.