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'Reversible cardiomyopathy' in patients with severe scorpion envenoming by Tityus serrulatus: evolution of enzymatic, electrocardiographic and echocardiographic alterations.

Severe scorpion envenoming is characterized by cardiocirculatory failure which may lead to pulmonary oedema. These are the major causes of death among victims of scorpion stings. Involvement of the heart has been attributed to the massive release of catecholamines and/or to a direct toxic effect of the venom on cardiac fibres, while pulmonary oedema has been considered to be of cardiogenic or non-cardiogenic origin. We present here the clinical, laboratory, electrocardiographic and echocardiographic data of 12 victims of severe Tityus serrulatus stings. These patients had important echocardiographic evidence of moderate to severe left ventricular (LV) dysfunction with diffuse LV hypokinesia and reduced ejection fraction. Seven developed pulmonary oedema. The clinical course of all the patients was satisfactory and the laboratory, electrocardiographic and echocardiographic changes returned to normal, usually within 1 week of the sting. The important alterations detected by echocardiography as early as during the 1st few hours after the sting, taken together with the enzymatic and electrocardiographic data, confirm that LV dysfunction is responsible, either alone or in combination with other factors, for the cardiac insufficiency and pulmonary oedema encountered in scorpion envenoming.

Adolescent↗

Severe scorpion envenomation in Brazil. Clinical, laboratory and anatomopathological aspects.

Scorpion stings in Brazil are important not only because of their incidence but also for their potential ability to induce severe, and often fatal, clinical situations, especially among children. In this report we present the clinical and laboratory data of 4 patients victims of scorpion stings by T. serrulatus, who developed heart failure and pulmonary edema, with 3 of them dying within 24 hours of the sting. Anatomopathologic study of these patients revealed diffuse areas of myocardiocytolysis in addition to pulmonary edema. The surviving child presented enzymatic, electrocardiographic and echocardiographic changes compatible with severe cardiac involvement, which were reversed within 5 days. These findings reinforce the need for continuous monitoring of patients with severe scorpion envenoming during the hours immediately following the sting.

Animals↗

Scorpion envenomation and serotherapy in Morocco.

A clinical and biologic study was conducted in Morocco to assess the efficiency of antivenom therapy for treating victims of scorpion stings. Epidemiologic and clinical data were collected from 275 patients envenomed by Androctonus mauretanicus mauretanicus and Buthus occitanus scorpions. Patients received antivenom or other drugs. Blood samples were collected at the time of hospital admission and 1 hr and 3 hr after treatment. Serum venom levels were quantified by using an ELISA. An association was found between clinical signs of envenoming and the level of venom in serum. Patients classified as grade II (moderate envenoming) had higher serum levels of venom level than patients classified as grade I (mild envenoming). At admission to the hospital, the mean venom concentration was not significantly different between the group not treated with antivenom, the group who received 2-5 ml of antivenom, and the group who received 10 ml of antivenom. A significant decrease in serum venom levels and an improvement in the clinical conditions were observed in patients administered 10 ml of antivenom. The lower decrease in serum venom levels in patients who received 2-5 ml of antivenom was due to lower doses of antivenom. No difference in the venom concentration was observed in patients who were not treated with antivenom. The absence of administration of antivenom increased the risk of developing clinical signs at the end of the hospitalization period. However, this risk was much higher when more than 1 hr elapsed between the time of the scorpion sting and the time of hospital admission. The results demonstrate that antivenom is effective in decreasing circulating venom and morbidity. Serotherapy is more efficient when given as soon as possible after envenomation and with adequate quantities of antivenom.

Adolescent↗

[Clinical evolution and circulating venom levels in scorpion envenomations in Morocco].

We conducted a clinical and biological study in Morocco in order to assess the efficacy of antivenom therapy against scorpion stings. Epidemiological and clinical data were collected in 275 patients envenomed by Androctonus mauretanicus mauretanicus and Buthus occitanus scorpions. Patients received antivenom or symptomatic drugs. Blood samples were collected upon hospital admission, at 1 hr and 3 hrs after the treatment. An enzyme linked immunosorbent assay (ELISA) was set up to quantify the venom levels in serum of envenomed patients. Mean serum venom concentrations showed an association between clinical signs and the venom level. The venom concentration at admission, in patients who received 10 ml of antivenom, was significantly reduced after antivenom therapy. The decrease was less important in patients who received only 2 to 5 ml of antivenom. No difference was shown in the venom concentration of patients not treated with antivenom. The clinical signs decreased significantly after antivenom treatment. The absence of antivenom administration increased the risk to develop clinical signs at the end of hospitalisation. This risk was much higher when the delay between scorpion sting and hospital admission increased. The results of our study have demonstrated the efficacy of antivenom in reducing circulating venom and symptoms. Antivenom therapy is more efficient when administered as soon as possible after envenomation and with appropriate quantities of antivenom. This study is favourable to the use of SAS but a prospective study would be useful to confirm these data.

Adolescent↗

[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.

Animals↗

Clinical and echocardiographic findings in patients with myocardial toxicity due to scorpion sting.

BACKGROUND: Myocardial toxicity following a sting by the Indian red scorpion (Mesobuthus tamulus) is a life-threatening medical emergency. A perusal of the published literature suggests that this problem has seldom been studied systematically. METHODS: We retrospectively studied the clinical presentation and echocardiographic findings in 24 patients (mean [SD] age 23.2 [11.7] years; 19 males) with myocardial toxicity caused by the sting of an Indian red scorpion (Mesobuthus tamulus). They were treated with inotropic support and diuretics depending on the requirement. At admission, oral L-carnitine was administered in a dose of 1980 mg/day in three divided doses till the left ventricular (LV) function normalized. None of the patients received digitalis, prazosin, hydrocortisone or antivenin. RESULTS: Extreme anxiety and severe pain at the site of sting were present in all the patients. Hypotension (n = 19), pulmonary oedema (n= 15) and acute renal failure (n=8) were the other presenting features. Chest X-ray revealed cardiomegaly in 8 and pulmonary oedema in 13 patients. Serum creatinine phosphokinase levels were elevated more than two times the upper limit of normal (200 IU/L) in 22 patients (92%). The mean duration of hospitalization was 5 days (range 3- 11 days). L-carnitine treatment resulted in significant reduction in the LV diameter (mm) in diastole (47.6 [6.2] v. 42 [6.1], p < 0.01) and systole (42 [7.1] v. 28.2 [4], p<0.001); end-diastolic volume (ml) (108.7 [31.9] v. 81 [26.7], p <0.01) and end-systolic volume (ml) (81.3 [30.9] v. 31.1 [10.7], p < 0.001); and significant improvement in the stroke volume (ml) 27.8 [13.2] v. 61.7 [6.2], p<0.001) and ejection fraction (%) (25.5 [12.8] v. 61.2 [6.5], p<0.001). All the patients responded well to treatment and none died. CONCLUSION: Our initial observations suggest a potential benefit with additional oral L-carnitine treatment in patients with myocardial toxicity caused by scorpion sting presenting with hypotension and severe LV dysfunction. These findings merit further study.

Adolescent↗

[The electrocardiographic changes in patients stung by scorpions].

Scorpion sting is a hazardous and potentially lethal condition. Venom of some variety of scorpion can cause dramatic cardiovascular and electrocardiographic changes, that have been related to heart stimulation by autonomous nervous system. We prospectively studied 722 patients following scorpion sting. Mean age for the group was 25.5 +/- 18.3 years. 67% were less than 30 years of age. In 294 patients (40.7%) we found electrocardiographic changes. These cases were followed until those changes disappeared. First degree atrioventricular block was found in 10.2%. Intraventricular conduction disturbances in 12.8% with predominance of right bundle branch block. In 11% we found arrhythmias. In 15% reversible ventricular repolarization changes. Of this no one died. This lack of mortality could be attributed to a prompt therapeutic intervention.

Age Factors↗

Scorpion envenomation.

A potentially lethal neurotoxin-producing scorpion, Centruroides sculpturatus, exists in the southwestern United States. The most common symptoms of envenomation of 24 patients included local pain, restlessness, and roving eye movements. In this series 80% of cases were in children less than 10 years of age. Pain at the site of the sting was a predominant symptom in the patient more than 10 years of age; however, extreme and perpetual restlessness was the most common symptom in the younger patient. The diagnosis in children is usually made by clinical presentation alone since the site of the sting cannot be identified and children may not communicate the history of the sting. The most commonly used chemotherapeutic agent is phenobarbital. There is no evidence, however, that this drug decreases morbidity or mortality, and massive doses of phenobarbital were associated with two respiratory arrests in this series. The nature of scorpions and their venoms is discussed. Research is needed regarding the use of sympathetic blocking agents in scorpion envenomation.

Animals↗

The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily.

Animal toxins are highly reticulated and structured polypeptides that adopt a limited number of folds. In scorpion species, the most represented fold is the alpha/beta scaffold in which an helical structure is connected to an antiparallel beta-sheet by two disulfide bridges. The intimate relationship existing between peptide reticulation and folding remains poorly understood. Here, we investigated the role of disulfide bridging on the 3D structure of HsTx1, a scorpion toxin potently active on Kv1.1 and Kv1.3 channels. This toxin folds along the classical alpha/beta scaffold but belongs to a unique family of short-chain, four disulfide-bridged toxins. Removal of the fourth disulfide bridge of HsTx1 does not affect its helical structure, whereas its two-stranded beta-sheet is altered from a twisted to a nontwisted configuration. This structural change in HsTx1 is accompanied by a marked decrease in Kv1.1 and Kv1.3 current blockage, and by alterations in the toxin to channel molecular contacts. In contrast, a similar removal of the fourth disulfide bridge of Pi1, another scorpion toxin from the same structural family, has no impact on its 3D structure, pharmacology, or channel interaction. These data highlight the importance of disulfide bridging in reaching the correct bioactive conformation of some toxins.

Amino Acid Sequence↗

Deduction of functional peptide motifs in scorpion toxins.

Scorpion toxins are important physiological probes for characterizing ion channels. Molecular databases have limited functional annotation of scorpion toxins. Their function can be inferred by searching for conserved motifs in sequence signature databases that are derived statistically but are not necessarily biologically relevant. Mutation studies provide biological information on residues and positions important for structure-function relationship but are not normally used for extraction of binding motifs. 3D structure analyses also aid in the extraction of peptide motifs in which non-contiguous residues are clustered spatially. Here we present new, functionally relevant peptide motifs for ion channels, derived from the analyses of scorpion toxin native and mutant peptides.

Amino Acid Motifs↗

Moving pieces in a proteomic puzzle: mass fingerprinting of toxic fractions from the venom of Tityus serrulatus (Scorpiones, Buthidae).

Scorpion venoms are very complex mixtures of molecules, most of which are peptides that display different kinds of biological activity. These venoms have been studied in the light of their pharmacological targets and their constituents are able to bind specifically to a variety of ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins that modulate Na(+), K(+), Ca(++) and Cl(-) currents have been described in scorpion venoms. Mass spectrometry was employed to analyze toxic fractions from the venom of the Brazilian scorpion Tityus serrulatus in order to shed light on the molecular composition of this venom and to facilitate the search for novel pharmacologically active compounds. T. serrulatus venom was first subjected to gel filtration to separate its constituents according to their molecular size. The resultant fractions II and III, which account for 90 and 10% respectively of the whole venom toxic effect, were further analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), on-line liquid chromatography/electrospray mass spectrometry (LC/ESMS) and off-line LC/MALDI-TOFMS in order to establish their mass fingerprints. The molecular masses in fraction II were predominantly between 6500 and 7500 Da. This corresponds to long-chain toxins that mainly act on voltage-gated Na(+) channels. Fraction III is more complex and predominantly contained molecules with masses between 2500 and 5000 Da. This corresponds to the short-chain toxin family, most of which act on K(+) channels, and other unknown peptides. Finally, we were able to measure the molecular masses of 380 different compounds present in the two fractions investigated. To our knowledge, this is the largest number of components ever detected in the venom of a single animal species. Some of the toxins described previously from T. serrulatus venom could be detected by virtue of their molecular masses. The interpretation of this large set of data has provided us with useful proteomic information on the venom, and the implications of these findings are discussed.

Amino Acid Sequence↗

Tamulustoxin: a novel potassium channel blocker from the venom of the Indian red scorpion Mesobuthus tamulus.

We have characterized tamulustoxin, a novel 35-amino-acid peptide found in the venom of the Indian red scorpion (Mesobuthus tamulus). Tamulustoxin was identified through a [125I]toxin I screen, designed to identify toxins that block voltage-activated potassium channels. Tamulustoxin has also been cloned by RT-PCR, using RNA extracted from scorpion venom glands. Tamulustoxin shares no homology with other scorpion venom toxins, although the positions of its six cysteine residues would suggest that it shares the same structural scaffold. Tamulustoxin rapidly inhibited both peak and steady-state currents (18.9 +/- 1.0 and 37 +/- 1.1%, respectively) produced by injecting CHO cells with mRNA encoding the hKv1.6 channel.

Amino Acid Sequence↗

Purification, characterization, and primary structure of four depressant insect-selective neurotoxin analogs from scorpion (Buthus sindicus) venom.

Four depressant insect-selective neurotoxin analogs (termed Bs-dprIT1 to 4) from the venom of the scorpion Buthus sindicus were purified to homogeneity in a single step using reverse-phase HPLC. The molecular masses of the purified toxins were 6820.9, 6892.4, 6714.7, and 6657.1 Da, respectively, as determined by mass spectrometry. These long-chain neurotoxins were potent against insects with half lethal dose values of 67, 81, 103, and 78 ng/100 mg larva and 138, 160, 163, and 142 ng/100 mg cockroach, respectively, but were not lethal to mice even at the highest applied dose of 10 microg/20 g mouse. When injected into blowfly larvae (Sarcophaga falculata), Bs-dprIT1 to 4 induced classical manifestations of depressant toxins, i.e., a slow depressant flaccid paralysis. The primary structures of Bs-dprIT 1 to 4 revealed high sequence homology (60-75%) with other depressant insect toxins isolated from scorpion venoms. Despite the high sequence conservation, Bs-dprIT1 to 4 showed some remarkable features such as (i) the presence of methionine (Met(6) in Bs-dprIT1 and Met(24) in Bs-dprIT2 to 4) and histidine (His(53) and His(57) in Bs-dprIT1) residues, i.e., amino acid residues that are uncommon to this type of toxin; (ii) the substitution of two highly conserved tryptophan residues (Trp43 --> Ala and Trp53 --> His) in the sequence of Bs-dprIT1; and (iii) the occurrence of more positively charged amino acid residues at the C-terminal end than in other depressant insect toxins. Multiple sequence alignment, sequence analysis, sequence-based structure prediction, and 3D homology modeling studies revealed a protein fold and secondary structural elements similar to those of other scorpion toxins affecting sodium channel activation. The electrostatic potential calculated on the surface of the predicted 3D model of Bs-dprIT1 revealed a significant positive patch in the region of the toxin that is supposed to bind to the sodium channel.

Amino Acid Sequence↗

Evidence of myocardial ischaemia in severe scorpion envenomation. Myocardial perfusion scintigraphy study.

OBJECTIVE: To explore the myocardial perfusion by thallium-201 scintigraphy for patients with evidence of myocardial damage after scorpion envenomation. DESIGN: Prospective study over 1-year period. SETTING: Medical intensive care unit of a university hospital (Sfax, Tunisia). PATIENTS: We have prospectively included six patients admitted for scorpion envenomation over a period of 1 year in the 22-bed intensive care unit (ICU) of our university hospital. The evidence of myocardial damage was confirmed by electrocardiography and echocardiography in all patients. Myocardial perfusion scintigraphy ((201)Tl scintigraphy) coupled with radionuclide ventriculography ((99m)Tc) was performed for all patients, occurring 32 h on average (range 12-72 h) after the sting. RESULTS: Radionuclide ventriculography was abnormal in all cases; the abnormalities observed were similar to those observed by echocardiography. Moreover (201)Tl scintigraphy showed evidence of myocardial hypoperfusion in all cases. The myocardial hypoperfusion grade and localisation were more marked in the abnormal localisation shown by echocardiography and electrocardiography, compared to the normal wall. Repeated studies, obtained only in two patients within 6 and 15 days, respectively, showed considerable, but not complete, improvement of wall motion and myocardial perfusion. Segments with improved perfusion showed greatly improved regional wall motion. CONCLUSION: This study confirms the evidence of myocardial hypoperfusion after severe scorpion envenomation.

Adult↗

Adaptive evolution of scorpion sodium channel toxins.

Gene duplication followed by positive Darwinian selection is an important evolutionary event at the molecular level, by which a gene can gain new functions. Such an event might have occurred in the evolution of scorpion sodium channel toxin genes (alpha- and beta-groups). To test this hypothesis, a robust statistical method from Yang and co-workers based on the estimation of the nonsynonymous-to-synonymous rate ratio (omega = d(N)/ d(S)) was performed. The results provide clear statistical evidence for adaptive molecular evolution of scorpion alpha- and beta-toxin genes. A good match between the positively selected sites (evolutionary epitopes) and the putative bioactive surface (functional epitopes) indicates that these sites are most likely involved in functional recognition of sodium channels. Our results also shed light on the importance of the B-loop in the functional diversification of scorpion alpha- and beta-toxins.

Adaptation, Physiological↗

Characterization of the transcript for a depressant insect selective neurotoxin gene with an isolated cDNA clone from the scorpion Buthotus judaicus.

The poly(A)+ mRNA isolated from the venomous terminal segments of the scorpion Buthotus judaicus was reversed transcribed into cDNA. PCR amplification of the cDNA in presence of oligonucleotide primers prepared on basis of the known amino acid sequence of the depressant insect toxin II yielded a 125 bp long product. This fragment was cloned and its sequence determined. The deduced amino acid sequence has revealed a complete homology with the amino acid sequence of the toxin. This clone was used to probe a Northern blot resolving the poly(A)+ and poly(A)- fractions derived from the scorpion. An organ specific 360 nucleotide transcript which might be the processed product of a approximately 4.0 kb precursor was elucidated. This cDNA clone may pave the way for a molecular genetic approach to study the structure-function relationship of scorpion selective insect toxins.

Amino Acid Sequence↗

Acute pancreatitis in children following envenomation by the yellow scorpion Leiurus quinquestriatus.

Plasma immunoreactive cationic trypsin (ICT), which is a specific and highly sensitive indicator of pancreatic injury, was measured in 14 children with signs of systemic envenomation following a sting by the scorpion Leiurus quinquestriatus. High ICT levels were found in 13 children (93%), indicating that acute pancreatitis is a common complication of envenomation by this scorpion. The pancreatitis may account for the abdominal pain and vomiting commonly seen in scorpion envenomation and may also contribute to the agitation and discomfort noted in young children.

Acute Disease↗