Black scorpion envenomation: two cases and review of the literature.

Scorpion envenomation is quite common in India, southeast Asia, the U.S. southwest, and Israel (in the Negev and around Jerusalem). Yellow scorpion is considered the most dangerous scorpion that causes cardiac toxicity. Two patients are described, who lived in a nonendemic area of yellow scorpions and were envenomated by the black scorpion. Both suffered temporary cardiac involvement (manifested by electrocardiographic changes) which reverted to a normal pattern within 24 h. These are the first two cases that have been reported (from black scorpion envenomation) and indicate that the toxin of the black scorpion is also cardiotoxic, but much less than the "yellow scorpion" toxin.     

血清肌钙蛋白I、肌酸激酶同工酶-Ⅱ测定在肾衰患者中的作用

目的：观察慢性肾功能衰竭患者心肌肌钙蛋白、肌酸激酶同工酶一Ⅱ的异常变化,并分析其与预后的关系。方法：应用ACCESS2化学发光法检测慢性肾功能衰竭患者心肌肌钙蛋白、肌酸激酶同工酶一Ⅱ,彩色多普勒测定左室射血分数（EF）,同时对心肌肌钙蛋白升高患者进行APACHEⅡ评分。结果：48例患者血清肌钙蛋白I升高率为44．4％;APACHEⅡ评分在心肌肌钙蛋白升高患者中明显升高;血清肌钙蛋白I、肌酸激酶同工酶-Ⅱ同时升高患者,心衰发生率高。结论：慢性肾功能衰竭患者心肌损伤较为普遍且部分为亚临床损伤,需谨慎对待。     

Neural control of the endocrine rat heart.

Although atrial stretch is the accepted stimulus for atrial natriuretic factor (ANF), in vivo studies suggest a stretch-independent, neurally induced ANF release mechanism. Thus the hypothesis that cardiac nerves can stimulate ANF secretion was tested in the Langendorff-perfused, paced rat heart. Venom from the scorpion Centruroides sculpturatus was used to activate neuronal sodium channels, veratridine was added to activate sodium channels (predominantly in myocytes), and electrical stimulation was applied to the right atrial appendage. The efficacy of nerve stimulation was verified by measurements of increased neuropeptide Y in the effluent. ANF levels in the effluent increased by 120% over baseline with 0.5 microM scorpion venom and by 88% with 0.5 microM veratridine (P < 0.01). Cardiac mechanics did not explain the large, concentration-dependent ANF response to the scorpion venom, since changes in the left ventricular developed pressure were small, opposite to those induced by veratridine, and unaffected by sympathectomy or adrenergic receptor blockade. Prior chemical sympathectomy and adrenergic receptor blockade almost abolished the ANF response to scorpion venom but hardly affected the ANF response to veratridine. Addition of 1 microM tetrodotoxin abolished all ANF responses. Electrical stimulation of the atrial appendage increased the ANF secretion by 60.2% (P < 0.02), in conjunction with neuropeptide Y, whereas control stimulations were ineffective. These studies unequivocally demonstrate that stimulation of cardiac sympathetic nerves potently stimulates ANF secretion.     

Insulin administration reverses the metabolic and electrocardiographic changes in acute myocarditis induced by Indian red scorpion (Buthus tamulus) venom in experimental dogs

Acute myocarditis was produced by injection of 4 mg/kg Indian red scorpion (Buthus tamulus) venom in dogs. Several rhythm changes, conduction defects, infarction-like pattern and many other ECG abnormalities; hyperglycemia, reduced insulin secretion, rise in free fatty acids along with fall in triglycerides; depletion of glycogen content of atria, ventricles, liver and skeletal muscles was noticed within 20-30 minutes after scorpion envenomation. Ten units of crystalline insulin was given i.v. at this time. All the arrhythmias, conduction defects and other ECG abnormalities disappeared after intervention with insulin. The sinus rhythm persisted for a duration of 120 minutes till the animals were sacrificed. Reduction in free fatty acids along with a rise in triglycerides; glycogenesis in liver, cardiac and skeletal muscles was observed at the time when ECG tracing was normal. It is suggested that catecholamines released during autonomic storm in scorpion poisoning suppress insulin secretion. These in turn result in glycogenolysis; lipolysis resulting in increased free fatty acids and produce arrhythmias. Insulin administration results in glycogenesis; lipogenesis and stops arrhythmias.     

Peptide toxins as probes of ryanodine receptor structure and function

Toxins from scorpion venom are emerging as useful ligands for structure/function studies of ryanodine receptors (RyR), the sarcoplasmic reticulum Ca(2+) release channels that elevate intracellular Ca(2+) to elicit contraction of cardiac and skeletal muscle. Imperatoxin A (IpTx(a)), a 3.7 kDa peptide from the African scorpion P. imperator, is an agonist of RyRs which, similar to the alkaloid ryanodine, binds with high affinity to the RyR protein and induces the appearance of a long-lived subconductance state. Imperatoxin I (IpTx(i)), a 15 kDa heterodimeric protein from the same venom that displays phospholipase A(2) activity, inhibits RyRs without a physical interaction with the channel protein, by releasing free fatty acids into the incubation medium. IpTx(a) and IpTx(i) are the first of a group of peptide probes of RyRs with diverse mechanism of action which overcome some of the undesirable characteristics of ryanodine.     

东亚钳蝎毒诱发大肠癌细胞凋亡的电镜观察

东亚钳蝎毒素是东亚钳蝎毒腺细胞分泌的一种具有多种生物活性的小分子多肽类物质。我们应用体外细胞培养的方法,已证实蝎毒素对大肠癌细胞具有显著的抑杀作用。为进一步探讨蝎毒素抑杀肿瘤细胞的机理,我们用东亚钳蝎毒素灌胃治疗大鼠实验性大肠癌,详细研究了用药后大肠肿瘤细胞超微结构的变化,结果表明,蝎毒素能诱发大肠癌细胞程序化死亡,本实验详尽地观察了大肠癌肿瘤细胞程序化死亡的基本过程,这种作用可能是蝎毒抗肿瘤的重要途径之一。     

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.     

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.     

Membrane potential dependent binding of scorpion toxin to action potential Na+ ionophore.

Depolarization of neuroblastoma cells causes a 70-fold increase in the apparent dissociation constant KD for scorpion toxin enhancement of activation of the action potential Na+ ionophore by veratridine and a large increase in the rate of reversal of scorpion toxin action. Depolarization also inhibits binding of 125I-labeled scorpion toxin to a small number of saturable binding sites on electrically excitable neuroblastoma cells and increases the rate of dissociation of scorpion toxin from these sites. The results suggest that scorpion toxin binds to a regulatory component of the action potential Na+ ionophore whose conformation changes on depolarization.     

Scorpion toxins targeted against the sarcoplasmic reticulum Ca(2+)-release channel of skeletal and cardiac muscle.

We report the purification of two peptides, called "imperatoxin inhibitor" and "imperatoxin activator," from the venom of the scorpion Pandinus imperator targeted against ryanodine receptor Ca(2+)-release channels. Imperatoxin inhibitor has a M(r) of approximately 10,500, inhibits [3H]ryanodine binding to skeletal and cardiac sarcoplasmic reticulum with an ED50 of approximately 10 nM, and blocks openings of skeletal and cardiac Ca(2+)-release channels incorporated into planar bilayers. In whole-cell recordings of cardiac myocytes, imperatoxin inhibitor decreased twitch amplitude and intracellular Ca2+ transients, suggesting a selective blockade of Ca2+ release from the sarcoplasmic reticulum. Imperatoxin activator has a M(r) of approximately 8700, stimulates [3H]ryanodine binding in skeletal but not cardiac sarcoplasmic reticulum with an ED50 of approximately 6 nM, and activates skeletal but not cardiac Ca(2+)-release channels. These ligands may serve to selectively "turn on" or "turn off" ryanodine receptors in fragmented systems and whole cells.     

An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart

Voltage-gated sodium channels composed of pore-forming alpha and auxiliary beta subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of distinct sodium channel subtypes have not been clearly defined. Immunocytochemical studies show that the principal cardiac pore-forming alpha subunit isoform Na(v)1.5 is preferentially localized in intercalated disks, whereas the brain alpha subunit isoforms Na(v)1.1, Na(v)1.3, and Na(v)1.6 are localized in the transverse tubules. Sodium currents due to the highly tetrodotoxin (TTX)-sensitive brain isoforms in the transverse tubules are small and are detectable only after activation with beta scorpion toxin. Nevertheless, they play an important role in coupling depolarization of the cell surface membrane to contraction, because low TTX concentrations reduce left ventricular function. Our results suggest that the principal cardiac isoform in the intercalated disks is primarily responsible for action potential conduction between cells and reveal an unexpected role for brain sodium channel isoforms in the transverse tubules in coupling electrical excitation to contraction in cardiac muscle.     

HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels.

The persistent infection of human glial cells with HIV-1 is characterized by prominent expression of the Nef protein. In order to evaluate the possible role of Nef in the development of HIV-1-associated neurological disorders, we compared Nef with known neuroactive proteins. We found that HIV Nef shares sequence and structural features with scorpion peptides known to interact with K+ channels. Sequence similarity encompasses two distinct regions of scorpion peptides. Based on crystallography data, both regions in scorpion peptides cooperate in forming a common domain stabilized by ion pairs between charged amino-acid residues. Recombinant Nef protein, as well as a synthetic part of a scorpion channel active peptide (M10), reversibly increased the total K+ current of chick dorsal root ganglions in patch-clamp experiments without killing the cells. These results indicate that a region conserved in HIV Nef and scorpion peptides concurs in both structure and electrophysiological activity and suggest that Nef, like scorpion peptides, may affect neuronal cell function.     

Scorpion venom decreases lung liquid clearance in rats

It has been reported that scorpion venom causes respiratory failure and pulmonary edema. However, the effects of this toxin on lung edema clearance have not been previously studied. We examined the effects of scorpion (Tityus serrulatus) venom on the ability of the lung to clear fluid and on alveolar epithelial Na,K-ATPase. The wet-to-dry lung weight ratio was increased in anesthetized rats injected intraperitonally with scorpion venom. Lung edema clearance decreased by up to approximately 60% in rats injected with the venom. Na,K-ATPase alpha1- and beta1-subunit protein abundance and activity decreased at the basolateral membranes of alveolar epithelial type II cells incubated with scorpion venom as compared with that of control animals. There was no difference in cell injury in alveolar epithelial type II cells incubated with scorpion venom for 60 minutes compared with that of control animals. We provide here the first evidence that scorpion venom decreases lung liquid clearance, probably by downregulating Na,K-ATPase in the alveolar epithelium.     

Cardiac dysfunction and pulmonary edema following scorpion envenomation

Cardiac dysfunction with pulmonary edema following scorpion envenomation (SE) has been documented only in a few isolated case reports. We conducted a systematic hemodynamic study in five consecutive patients (mean age, 21.6 +/- 8 years) presenting with pulmonary edema occurring a few hours (9.6 +/- 5.2 hours) after SE. All patients had increased pulmonary capillary wedge pressure (mean, 25 +/- 1.8 mm Hg) while the systemic vascular resistance was elevated only in one. The stroke volume index was markedly depressed (21.7 +/- 3.6 ml/sq m) whereas cardiac index was normal or slightly decreased (2.5 +/- 0.4 L/min/sq m). Cerebral infarct and sudden cardiac arrest were the cause of death in two patients. In the three survivors, all the hemodynamic disturbances and respiratory abnormalities disappeared within a few days. We conclude that cardiac dysfunction was found in all five patients and this was reversible in the three surviving the acute episode.     

Effect of toxin II isolated from scorpion venom on action potential and contraction of mammalian heart.

The effects of chemically pure toxin II (T_II, 0.2 to 5.0 μg) obtained from the venom of scorpion Androctonus australis were studied in the isolated perfused heart of adult rat, guinea-pig and young rabbit and in isolated superfused new-born rat heart. Contraction and cellular action potentials were recorded at 24 to 25°C. Injections of T_II produced a marked and persistent increase in amplitude and duration of the ventricular and atrial action potential plateau and a positive inotropic effect in normal as well as in reserpinized rat. Tetrodotoxin (TTX, 1 to 2 μg), calcium-rich media (10 mm) and procaine (15 μg) suppressed the T_II-induced lengthening of the response; this lengthening was not suppressed by manganese. In calcium-free Tyrode solution containing manganese (1 to 4 mm) T_II induced a small contraction suppressed by TTX. It is concluded that in rat heart, T_II increases the plateau by slowing down the inactivation of the sodium conductance or by inducing an incomplete sodium inactivation. This effect favors (i) indirectly, the penetration of calcium through the slow channel and (ii) the development of the tonic component of cardiac contraction; both effects are responsible for the positive inotropic effect. In guinea-pig and rabbit heart, action potential was not lengthened by T_II; this observation suggests the existence of species differences regarding the effects of the scorpion toxin on cardiac membranes.     

Scorpion stings in Australia: five definite stings and a review

Despite scorpions being locally abundant in many parts of Australia, scorpion sting is a poorly defined clinical condition in Australia. Many health-care workers are unaware of the effects of their stings and scorpions are often feared based on their international reputation. Five scorpion stings that occurred in different parts of Australia where the scorpion was caught at the time of the sting and identified by a professional arachnologist are reported in the present paper. The spectrum of clinical effects of scorpion stings in Australia and the potential for significant effects are discussed. These cases and recent prospective case series demonstrate that in Australia scorpion stings cause only minor effects. The main effect is localized pain lasting for several hours, associated less commonly with systemic effects, local numbness and paraesthesia. Most stings are from smaller scorpions from the family Buthidae and often occur indoors at night. The stings from Australian buthid scorpions cause more severe effects than from the larger species in the families Urodacidae (genus Urodacus) and Liochelidae (genus Liocheles).     

Scorpion bite prevalence and complications: report from a referral centre in southern Iran

In this study we describe the clinical features of scorpion bites in southern Iran. The records of scorpion bite victims from January 2000 to January 2009 were obtained from the record library of the Shiraz Nemazi Hospital, Shiraz, Iran. A total of 232 scorpion bite patients were included. Only 14 patients (6%) developed systemic complications. Acute renal failure (ARF) and disseminated intravascular coagulation (DIC) were the most prevalent systemic complications. The renal toxicity of scorpion envenomation is mostly due to Hemiscorpius lepturus stings and this complication is more common in younger children. This may be due to a higher ratio of venom to body mass compared with adults. H. lepturus venom is naturally cytotoxic and may bind directly to kidney tissue causing tubular injury and inducing DIC and haemolysis.     

全蝎纯化液对实验性动脉血栓形成t-PA、PAI-1的影响

目的观察全蝎纯化液对新西兰白兔颈总动脉血栓形成组织型纤溶酶原激活物(t-PA)、纤溶酶原活化物抑制剂(PAI-1)、血小板计数(Pt)的变化。方法将50只健康新西兰白兔随机分成5组:空白组、模型组、全蝎纯化液大剂量组(20mg/kg)、全蝎纯化液中剂量组(10mg/kg)和全蝎纯化液小剂量组(5mg/kg)。耳缘静脉注射药物(空白组、模型组注射同等体积的生理盐水)后,采用H2O2损伤新西兰白兔颈总动脉制备血栓模型,造模2h后,采血并取血栓,酶联免疫吸附法(ELISA法)检测血浆t-PA、PAI-1的含量。结果与空白组比较,模型组t-PA明显降低,PAI-1明显升高,差异有统计学意义(P<0.01);与模型组相比,全蝎纯化液各剂量组能明显抑制PAI-1活性,增加t-PA活性,差异均有统计学意义(P<0.01),而各组的血小板计数差异无统计学意义(P>0.05)。结论全蝎纯化液各剂量组可明显促进血浆t-PA的分泌,抑制血浆PAI-1活性,提示全蝎纯化液抗血栓作用机制可能与其促纤溶作用有关。     

Hemolytic-uremic syndrome secondary to scorpion envenomation (apropos of 2 cases)

HUS was recently described following scorpion sting. We report 2 cases of HUS in the intensive care unit of a university hospital. Two children aged respectively 10 months and 1 year were admitted in the ICU after severe scorpion envenomation (with coma and pulmonary oedema) having required dobutamine and mechanical ventilation. Evolution was marked with acute anaemia without bleeding requiring blood transfusion, acute renal failure, low platelets and signs of haemolysis. Our experience and the previously reported case suggest that scorpion sting could be added to the list of causes of the HUS.     

Myocardial damage with life-threatening arrhythmia due to a scorpion sting

Yellow scorpion venom is known to evoke cardiovascular responsesand cause severe myocardial damage in man. Life-threateningarrhythmias in such cases are rare. This work describes twosuch cases, and discusses the problems posed by ventriculararrhythmias in cases of scorpion sting.