Histopathological changes and inflammatory response induced by Tityus discrepans scorpion venom in rams.

Anesthetized rams envenomed s.c. with 40 microg/kg Tityus discrepans scorpion venom developed fasciculation, hypothermia, polyuria, pulmonary wet rales, tachypnea, respiratory distress and arrhythmia. Rams developed a cascade of inflammation reactions, characterized by activation of macrophages, fibroblasts and neutrophils, neutrophil infiltration and aggregation, vasculitis, arteritis and abundant fibrin deposition. At the inoculation site, venom was detected by immunohistochemistry in the extra cellular matrix, lymphatic vessels' and venules' lumen, inside macrophages and surrounding nerves. Extra cellular matrix was degraded at the inoculation site perhaps by activated neutrophils. Envenoming produced hepatocytes with Mallory body-like vacuoles which may be due to the increased plasmatic levels of TNF-alpha and IL6. Venom produced degranulation and vacuolization of acinary cells as well as interstitial swelling and necrosis. Necrosis of the Langerhan's islets occurred occasionally. Lungs showed the most deleterious effects developing wall collapse and necrosis, diffuse injury of the alveolar capillary barrier, interstitial and alveolar fibrin deposits with strong neutrophil infiltration. Massive infiltration of lymphocytes and macrophage occurred in the intestinal submucose, to the point that it modified villi and intestinal folding morphology. Envenomation developed a marked leukocyte aggregation surrounding nerves at the inoculation site. This study reveals that beyond its neurotoxicity, Tityus venom produces a severe and widespread inflammatory syndrome, expressed as histopathological changes at the site of inoculation, as well as in remote organs such as pancreas, lungs, intestine and liver. Our results suggest that not all remote targets are directly affected by the venom but that, as proposed earlier, are modified by inflammation by products produced elsewhere.

Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin G's F(ab')2 extrusion mechanism from blood to tissues.

Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin G's F(ab')(2) extrusion mechanism from blood to tissues. We measured pharmacokinetic parameters for T. discrepans venom in rams. Forty, 75 or 100 microg/kg venom were injected subcutaneously in the inner side of the thigh. Plasma venom content (venenemia) was determined by enzyme-linked immunosorbent assay (ELISA) from 0 to 300 min after injecting venom. Venenemia was fit to a three-compartment model (inoculation site, plasma and extra vascular extracellular space), it was assumed that the venom may also be irreversibly removed from plasma. Calculated time course of venom content shows that at any time no more that 30% of the venom is present in plasma. Venenemia peaks at 1h and decays afterwards. Fluorescently labelled antivenom [horse anti-TityusF(ab')(2) or fraction antigen binding, immuglobulin without Fc chain covalently bound to fluorescine or fluorescamine] pharmacokinetics was determined. Although F(ab')(2) molecular weight is >/=10 times bigger that toxin's, the rate of outflow of F(ab')(2) from blood to tissues was approximately 4 times faster than the venom's outflow. Venom content in the injection site decays exponentially for >6h, this prediction was confirmed immunohistochemically. Only approximately 5% of the venom is eliminated in 10h; approximately 80% of the venom is in the tissues after 2h and remains there for >10h.

Umbilical cord transection in twin-reverse arterial perfusion syndrome with the use of a coaxial bipolar electrode (Versapoint).

Umbilical-cord occlusion has been proposed for the treatment of twin-reverse arterial perfusion syndrome (TRAP). Transection of the umbilical cord is necessary in patients with monoamniotic or 'pseudomonoamniotic' TRAP to avoid subsequent cord entanglement and demise of the pump twin. We present a case of TRAP in which the umbilical cord was successfully ligated with suture and transected with the Versapoint electrode.