Hemodynamic and myocardial consequences of scorpion venom

The hemodynamic effects of scorpion venom (Leiurus quinquestriatus) and the mechanism of heart failure were investigated in two groups of anesthetized spontaneously breathing dogs. The effects of different adrenergic and cholinergic blocking agents on the venom-induced hemodynamic changes were also evaluated. In one group the venom was given before autonomic nervous system blocking agents and in a second group propranolol, atropine, phentolamine and hexamethonium alone or in different combinations were given before the venom. Complete autonomic nervous system blockade was induced in two animals to evaluate a possible direct myocardial effect of venom.The venom, a powerful arrhythmogenic agent stimulating the autonomic sympathetic nervous system and adrenals, induced dramatic hemodynamic increases in left ventricular systolic and diastolic pressures, pulmonary and systemic arterial pressures and left ventricular contractility. The hemodynamic data show clearly for the first time that pulmonary edema in severe scorpion envenomation is cardiac in origin, thus emphasizing the importance of the abnormal left ventricular hemodynamics. Heart failure is most probably the result of the interaction of several mechanisms that include a catecholamine-induced decrease in left ventricular compliance and increased impedance to left ventricular emptying and cardiac arrhythmias, all of which may impede left ventricular filling. The combination of propranolol and phentolamine was the most effective blocking agent in reversing the venom-induced hemodynamic changes. However, atropine was effective only when the venom-induced cholinergic effects dominated the clinical picture.     

Hemodynamics and microcirculation in a rat poisoned by scorpion venom]

The clinic table of serious scorpionic envenimation is dominated by cardiovascular and pulmonary perturbations. The physiopathology of cardiac failure in man as well as at animal is again badly elucidated. The aim of our study has consisted in evaluating the hemodynamic variations of the Rat poisoned by the venom of the Buthus occitanus scorpion and to contribute through the analyse of plasmatic concentrations of catecholamines and by an histomorphometric study of muscular microcirculation to explain the mechanism of the hemodynamic perturbations and cardiac failure. 51 rats corresponding to 9 groups (witness and poisoned) have been used. The venom of the scorpion Buthus occitanus has been administrated at 850 micrograms/kg. Two groups have been served for hemodynamic study, three groups for the dosage of catecholamines and four groups for histomorphometric study. It has been observed a biphasic variation of arterial pressure and cardiac frequency after venom injection. Four minutes after envenimation, the plasmatic level of catecholamines was strongly higher in the poisoned according to the witness one. Histomorphometric study of muscular skeletal microcirculation has shown a decrease of relative vascular volume contemporary with the increase of plasmatic catecholamines concentration and the peak of arteriel pressure appeared just after envenimation. 10 and 20 minutes after envenimation, the relative vascular volume has significantly increased as well as that interstitium according to witness lot. These hemodynamic perturbations can be attributed to the important dump in catecholamines. This hyperadrenergy was contemporary with decrease of relative muscular vascular volume. This decrease would be explained by a constriction of vessels. On the other hand, the second increase of the vascular relative volume suggests the possibility of development of venous stasis at the muscular microcirculation. It would be induced by a cardiac failure and/or the effect of vasoplegic mediators being able to entail an interstitial oedema in the muscular skeletal that would led to increase the relative interstitial volume observed in this study.     

蟾蜍毒素中毒致心律失常一例

蟾蜍毒素中毒导致心律失常极为罕见,现报道1例就诊于我院并成功救治的蟾蜍毒素中毒致心律失常病例. 患者,男,86岁,因"结肠癌术后3年,突发呼吸困难伴大汗30 min"入院.患者发现直肠癌肛周转移半个月,于1周前开始在肿物表面涂抹含蟾蜍毒素中药治疗,入院当日用药完毕约2h,突发呼吸困难,伴头晕、全身大汗及四肢厥冷,服用速效救心丸后未明显缓解,遂急人院就诊.主要体征:脉搏45次/min,血压90/45 mm Hg(1 mm Hg=0.133 kPa).     

Exocrine pancreatic response to the venom of the scorpion, Tityus trinitatis.

This paper records for the first time the exocrine pancreatic response to scorpion venom, in this case that of Tityus trinitatis, a scorpion endemic in Trinidad. The crude venom injected intravenously into fasting anaesthetised dogs induced a secretion of the exocrine pancreas. The secretion evoked was rich in enzymes.     

Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway

In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbβ3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.     

Snake venom poisoning in Greece. Experiences with 147 cases

BACKGROUND: Snake venom poisoning is a medical emergency requiring immediate attention. Bites from poisonous European snakes can lead to local tissue damage and systemic symptoms. Vipera ammodytes accounts for the most envenomation in Greece. METHODS: The demographic and epidemiological characteristics, clinical symptoms and signs, laboratory findings, treatment, and outcome of 147 consecutive victims of V. ammodytes admitted to our hospital from 1988 to 2003 were reviewed and analyzed. RESULTS: The most common symptoms and signs included fang marks (100%), pain (100%), swelling (98.64%), ecchymosis (60.54%), tachycardia (32.65%), fainting or dizziness (29.93%), fever (23.13%), enlargement of regional lymph nodes (17.69%), nausea (16.33%), hypotension (13.61%), and vomiting (12.93%). The main complications were reduced range of motion, thrombophlebitis, local hemorrhagic blister formation, skin bleeding, rhabdomyolysis, reduced sensation, acute renal failure, necrosis with tissue loss, carpal tunnel syndrome, compartment syndrome, Kounis syndrome, and digit amputation. CONCLUSIONS: A V. ammodytes bite is a potentially serious event that requires immediate hospital care. Yet, the majority of victims can be treated successfully with conservative methods. No deaths occurred in our series.     

Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway

In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbβ3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.     

Past, present, and future immunotherapy of snake venom poisoning

Management of snake venom poisoning with antivenin has been the time-proven and medically accepted standard in virtually every country, including the United States. All antivenins are equine in source, and administration to patients exposes them to all the adverse effects of heterologous antisera. The purity and specificity of neutralizing antibody titers in antivenin products vary among manufacturers. Research in the early 1980s demonstrated that immunosorbent affinity chromatography could purify a highly specific IgG(T) from equine hyperimmune antisera. This IgG(T) provided superior efficacy and reduced adverse effects as compared to commercial antivenin. The advent of newer biotechnical processes has now opened the doors for novel antibody and antibody fragment treatment of snake venom poisoning.     

Three-dimensional structure of a protein from scorpion venom: a new structural class of neurotoxins.

The three-dimensional crystal structure of variant-3 toxin from the scorpion Centruroides sculpturatus Ewing has been determined at 3 A resolution. Phases were obtained by use of K2PtCl4 and K2IrCl6 derivatives. The most prominent secondary structural features are two and a half turns of alpha-helix and a three-strand stretch of antiparallel beta-sheet, which runs parallel to the alpha-helix. The helix is connected to the middle strand of the beta-sheet by two disulfide bridges; a third disulfide bridge is located nearby. Several loops extend out of this dense core of secondary structure. The largest loop is joined to the COOH terminus of the molecule by the fourth disulfide bridge. The overall shape of the molecule resembles a right-hand fist: the alpha-helix runs along the knuckles of the fist; the beta-sheet lies along the second and third joints of the fingers; the thumb is defined by two short loops that are composed of residues 16-21 and residues 41-46; the wrist corresponds to the COOH-terminal stretch of residues 52-65 and a loop composed of residues 5-14; and the second joint of the little finger is near the NH2 terminus of the molecule. The alpha-carbon backbone displays a large flat surface that lies along the second joints of the fingers and the heel of the hand in the fist model. Several of the conserved residues in the scorpion neurotoxins are clustered on this surface, which may play a role in interactions of scorpion toxins with sodium channels of excitable membranes.     

Production of acute hemorrhagic pancreatitis in the dog using venom of the scorpion,Buthus quinquestriatus

Acute hemorrhagic pancreatitis has been produced in dogs by two separate intraarterial injections (20 and 10 μg/kg) of venom from the scorpionButhus quinquestriatus. Morphological changes related to the development of the disease were detectable by electron and light microscopy at 1 and 3 hr, respectively, following the injection of venom. Six hours following venom injection, widespread areas of hemorrhage and fat necrosis were observed on the surface of the pancreas and adjacent mesenteries. By 24 hr, areas of fat necrosis more than 1 cm in diameter were present on the surface of the pancreas. No free protease was found in pure pancreatic juice collected at 3, 6, 24, and 96 hr after the injection ofButhus quinquestriatus venom. Amylase concentrations in serum increased to a maximum sevenfold above the basal level at 6–8 hr after injection. Since acute hemorrhagic pancreatitis occurred both with and without pancreatic duct cannulation, it is likely that the pathological process is independent of any venom effect on papillary sphincter tone. The morphological characteristics of the experimental disease appear similar to those observed at autopsy in acute hemorrhagic pancreatitis in humans.     

Pathology of the alimentary tract in Salmonella typhimurium food poisoning.

The pathology of the alimentary tracts of nine patients dying of Salmonella typhimurium infection is reviewed. Two patients had previous gastric operations, supporting previous reports that such patients are more susceptible to food poisoning. Four had no parietal (oxyntic) cells in the gastric mucosa, suggesting hypo- or anacidity. Only one had acute gastritis. None had acute enteritis, but in half of the patients, subtle histological changes suggested an 'enteropathy'. Acute diffuse colitis with abundant crypt abscesses, without stromal abscesses in the lamina propria, was the most constant finding and reparative features started very early, and occurred in later deaths. Under ideal circumstances this crypt abscess is readily distinguished from that of idiopathic ulcerative colitis, but can be confused with the crypt abscess of acute bacillary (sonne) dysentery. While the florid colonic changes may have settled in the late deaths, active inflammation is commonly present in the appendix mucosa on histology. The pathology of the alimentary tract in S typhimurium infection differs from that of S typhi and S paratyphi infections. There is little evidence of gastroenteritis, although subtle changes occur in the stomach and small intestine. The features are those of acute diffuse colitis with histological appendicitis, distinguishable from idiopathic ulcerative colitis.     

Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications

A healthy man developed gastrointestinal symptoms after ingesting purported aphrodisiac pills. He had severe unrelenting bradycardia, hyperkalaemia, and acidosis. He rapidly developed severe life threatening cardiac arrhythmias and died after a few hours. He was found to have positive serum digoxin concentrations, although he was not taking digoxin. Toad venom poisoning is similar to digitalis toxicity and carries a high mortality. Cardiac glycoside poisoning can occur from ingestion of various plants and animal toxins, and the venom gland of cane toad (Bufo marinus) contains large quantities of cardiac glycosides. Toad venom, a constituent of an aphrodisiac, was considered responsible for the development of clinical manifestations and death in this patient. Digoxin specific Fab fragment has been reported to be beneficial in the treatment of toad venom poisoning. This report alerts physicians to the need to be aware of a new community toxic exposure, as prompt treatment with digoxin specific Fab fragment may be life saving. The treatment approach to patients with suspected toad venom poisoning is described.