Recent advances in the understanding of brown spider venoms: From the biology of spiders to the molecular mechanisms of toxins.

The Loxosceles genus spiders (the brown spiders) are encountered in all the continents, and the clinical manifestations following spider bites include skin necrosis with gravitational lesion spreading and occasional systemic manifestations, such as intravascular hemolysis, thrombocytopenia and acute renal failure. Brown spider venoms are complex mixtures of toxins especially enriched in three molecular families: the phospholipases D, astacin-like metalloproteases and Inhibitor Cystine Knot (ICK) peptides. Other toxins with low level of expression also present in the venom include the serine proteases, serine protease inhibitors, hyaluronidases, allergen factors and translationally controlled tumor protein (TCTP). The mechanisms by which the Loxosceles venoms act and exert their noxious effects are not fully understood. Except for the brown spider venom phospholipase D, which causes dermonecrosis, hemolysis, thrombocytopenia and renal failure, the pathological activities of the other venom toxins remain unclear. The objective of the present review is to provide insights into the brown spider venoms and loxoscelism based on recent results. These insights include the biology of brown spiders, the clinical features of loxoscelism and the diagnosis and therapy of brown spider bites. Regarding the brown spider venom, this review includes a description of the novel toxins revealed by molecular biology and proteomics techniques, the data regarding three-dimensional toxin structures, and the mechanism of action of these molecules. Finally, the biotechnological applications of the venom components, especially for those toxins reported as recombinant molecules, and the challenges for future study are discussed.

Local inflammatory reaction induced by Scolopendra viridicornis centipede venom in mice.

Centipede envenomation is generally mild, and human victims usually manifest burning pain, erythema and edema. Despite the abundance and ubiquity of these animals, centipede venom has been poorly characterized in literature. For this reason, the aim of this work was to investigate local inflammatory features induced by Scolopendra viridicornis centipede envenomation in mice, evaluating edema formation, leukocyte infiltration, production of inflammatory mediators, and also performing histological analysis. The highest edematogenic activity induced by the venom, determined by plethysmometry, was noticed 0.5 h after injection in mice footpad. At 24 h, edema was still detected in animals that received 15 and 60 µg of venom, and at 48 h, only in animals injected with 60 µg of venom. In relation to leukocyte count, S. viridicornis venom induced cell recruitment, mainly neutrophils and monocytes/macrophages, in all doses and time periods analyzed in comparison with PBS-injected mice. An increase in lymphocytes was detected especially between 1 and 24 h at 60 µg dose. Besides, eosinophil recruitment was observed mainly for 15 and 60 µg doses in early time periods. Edema formation and cell recruitment were also confirmed by histological analysis. Moreover, S. viridicornis venom stimulated the release of IL-6, MCP-1, KC, and IL-1ß. Conversely, S. viridicornis venom did not induce the release of detectable levels of TNF-α. We demonstrated that the edematogenic activity induced by S. viridicornis venom was of rapid onset, and the venom stimulated secretion of pro-inflammatory mediators which contribute to the inflammatory reaction induced by S. viridicornis venom in an experimental model.

Clinical and epidemiological features of definitive and presumed loxoscelism in Säo Paulo, Brazil

A retrospective study analysed 359 proven or presume cases of loxoscelism seen at the Hospital Vital Brazil, Instituto Butantan, Säo Paulo, Brazil, between 1985 and 1996. The spider was identified in 14 percent. The bites occurred predominantly in the urban areas (73 percent) between September and February. Patients > 14 years were commonest inflicted (92 percent) and 41 percent were bitten while getting dressed. Only 11 percent sought medical care within the first 12 hours post bite. Cutaneous loxoscelism was the commonest form presenting (96 percent); commonest manifestations were: pain (76 percent), erythema (72 percent), edema with enduration (66 percent), ecchymosis (39 percent). Skin necrosis occurred in 53 percent of patients, most frequently seen on trunk, tigh and upper arm, and when patients seek medical care more than 72 hours after bite. Local infection was detected in 12 patients (3 percent). Hemolysis was confirmed in 4 cases (1.1 percent). Generalised cutaneous rash, fever and headache were also observed in 48 percent of the total of patients. None of them had acute renal failure or died. Treatment usually involved antivenom administration (66 percent), being associated with corticosteroids (47 percent) or dapsone (30 percent). Presumptive diagnosis of loxoscelism may be established based on clinical and epidemiological findings. Further investigations are required to prove the value of antivenom and other treatment schedules