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We have shown that d-tubocurarine inhibits the effects of scorpion venom in striated muscles of the frog; we concluded that this venom acts mainly by releasing acetylcholine from the nerve terminal. Furthermore, scorpion venom is able to displace intracellular calcium.
Myocardiocytes of mice were cultured. Action potentials were recorded with microelectrodes inside the cells. Scorpion venom from Buthus martensii Karsch 3.75 or 7.5 micrograms.ml-1 decreased the duration of action potential and all of the depolarization concerned parameters of myocardiocytes. The Vmax, TP, APA behaved apparently in a dosage-dependent way. Restoration happened after washing out. Tetrodotoxin 2.5 micrograms.ml-1 acted in a similar way. Nimodipine 3.0 micrograms.ml-1 led to a decrease in action potential duration. BaCl2 0.1 mmol.L-1 elongated the action potential duration, while decreased the parameters concerned with depolarization. These results indicate that the scorpion venom has Na+ channel blocking action.
Three 35-amino acid peptide K+ channel toxins (pandinotoxins) were purified from the venom of the scorpion Pandinus imperaton the toxins are designated pandinotoxin (PiTX)-K alpha, PiTX-K beta, and PiTX-K gamma. In an 86Rb tracer flux assay on rat brain synaptosomes, all three toxins selectively blocked the component of the K(+)-stimulated 86Rb efflux that corresponds to a voltage-gated, rapidly inactivating (A-type) K+ current (IC50 = 6, 42, and 100 nM, respectively). These toxins blocked neither the noninactivating component of the K(+)-stimulated 86Rb efflux (corresponding to a delayed rectifier) nor the Ca(2+)-dependent component of the 86Rb efflux (i.e., a Ca(2+)-activated K+ current) in these terminals. PiTX-K alpha, which was expressed by recombinant methods, also blocked the Kv1.2 channel expressed in fibroblasts (IC50 = 32 pM). PiTX-K alpha and PiTX-K beta have identical amino acid sequences except for the seventh amino acid: a proline in PiTX-K alpha, and a glutamic acid in PiTX-K beta. They have substantial sequence homology, especially at the carboxyl termini, with another scorpion toxin, charybdotoxin (ChTX), which blocks both the Ca(2+)-activated and the rapidly inactivating. K(+)-stimulated 86Rb efflux components in synaptosomes and the Kv 1.2 channel PiTX-K gamma, however, has much less sequence homology. Conserved in all four toxins are three identically positioned disulfide bridges; an asparagine at position 30; and positive charges at positions 27, 31, and 34 (based on ChTX numbering). PiTX-K gamma is novel in that it has a fourth pair of cysteines. The PiTX structures were computer simulated, using ChTX as a model. We speculate that the three-dimensional structures of all three PiTXs resemble that of ChTX: a beta-sheet at the carboxyl terminus, containing three cysteines, is linked to the central alpha-helix by two disulfide bridges (C17-C35 and C13-C33) and to an extended amino-terminal fragment by the third disulfide bridge (C7-C28). Further analysis of the three-dimensional structures reveals differences that may help to explain the selectivity and affinity differences of these toxins.
Although the precise mechanism of the cardiovascular effects in man evoked by the venom of the yellow scorpion has yet to be completely elucidated, previous studies indicate that excessive adrenergic activity is present in many of the cases. This report describes two patients in whom yellow scorpion sting was followed by bradyarrhythmia with varying degrees of atrioventricular block which promptly regressed after the administration of atropine; this is consistent with a direct parasympathomimetic effect of the venom or with a central effect producing increased vagal tone. It is suggested that the cardiovascular actions of the venom may represent a wide spectrum of effects on the autonomic nervous system, ranging from the predominantly sympathomimetic to the predominantly parasympathomimetic.
1. A methyl-4-azidobenzimidyl (MAB) derivative of the alpha-scorpion toxin from Leiurus quinquestriatus (LqTx) specifically labels only the alpha subunit of the rat brain sodium channel in synaptosomes or in purified and reconstituted sodium-channel preparations. 2. Unlike previous photoreactive toxin derivaties, binding and photolabeling by MAB-LqTx are allosterically modulated by tetrodotoxin and batrachotoxin, as observed for native LqTx binding to sodium channels in synaptosomes. 3. Proteolytic cleavage of the alpha subunit photolabeled with MAB-LqTx shows that the label is located within a 60 to 70-kDa protease-resistant core structure in domain I of the sodium-channel alpha subunit. 4. MAB-LqTx will be valuable in further defining the structure-activity relationships at the alpha-scorpion toxin receptor site.
PURPOSE: The objective was to evaluate amphiphilic scorpion-like macromolecules (AScMs) as drug carriers for hydrophobic drugs. METHODS: Indomethacin (IMC) was incorporated into two AScM micelles (M12P5 and M12P2) by the O/W emulsion technique. The influences of IMC:polymer feed ratio and molecular weight of the hydrophilic block of AScMs on the micelle size, IMC entrapment efficiency and release behavior were investigated. Furthermore, cytotoxicity of the AScMs was evaluated with human umbilical vein endothelial cells (HUVEC). RESULTS: The maximal IMC entrapment efficiency in M12P5 and M12P2 micelles (72.3 and 20.2%, respectively) was obtained at ratios of 0.1 to 1 for indomethacin:polymer. The sizes of IMC-loaded M12P5 and Mi2P2 polymeric micelles were <20 nm with a narrow size distribution. In vitro release studies revealed that IMC released from MI2P5 and M12P2 polymeric micelles showed sustained release behavior during the 24 h of experiment. Additionally, M12P5 and M12P2 polymeric micelles did not induce remarkable cytotoxicity against HUVEC cells at concentrations up to 1 and 0.5 mM, respectively. CONCLUSION: The amphiphilic scorpion-like macromolecules may be useful as novel drug carriers because of their small size, ability to encapsulate hydrophobic drugs and release them in a sustained manner as well as low cytotoxicity.
Spring water from alpine catchments are important water resources but they can be vulnerable against faecal contamination. Potential faecal contamination sources are wildlife populations, pasturing activities, or alpine tourism. Unfortunately, no faecal source tracking method is available to date which is sensitive enough for appropriate spring water monitoring and source allocation. Our purpose was to develop a Duplex Scorpion real-time PCR approach for the specific and sensitive quantification of Bacteroides sp. 16S rDNA fragments from human and cattle origin. By the developed approach, detection of plasmids, carrying the respective biomarker sequence, was possible over a range of more than seven orders of magnitudes down to six copy numbers per PCR assay. Furthermore, the Duplex Scorpion real-time PCR allowed the specific quantification down to 50 targets in plasmid spiked spring water matrices. Results indicate that microbial source tracking appears feasible in spring water habitats by probe-based real-time PCR technologies. However, preliminary testing of the established approach on faecal samples collected from a representative alpine habitat did not allow unambiguous source allocation in all cases. In the future, the available sequence database has thus to be widened to allow reliable source tracking in alpine spring watersheds and even expand this approach to other potential faecal sources.
A novel quantitative real-time PCR method using the duplex scorpion primer for detection of Chlamydia trachomatis DNA was developed and validated. The assay employs a duplex primer; its most important feature is the intramolecular probe-target interaction. The assay had many prominent characteristics. (i) The duplex probe is simpler to synthesize and significantly easier to purify than TaqMan probe because that the fluorescent dye pair and the quencher pair are in different oligonucleotides. (ii) The method has high sensitivity, specificity, intra- and interassay reproducibilities. (iii) The assay has a quantitative dynamic range of 25 to10(9) genome copies per reaction mixture. (iv) The scorpion system can identify 98.6% samples in the validation panel without retest. There were 81 positive samples and 67 negative samples, which were confirmed by two FDA-approved NAATs (the Roche Amplicor PCR assay, Abbott LCR kit) and our new method. Any two positive results out of the possible three-comparator results would define the infected-patient gold standard. Of the positive samples, 79 (97.5%) were found positive (ranging from 31 to 227,648 copies/microl, M=4219 copies/microl), whereas no negative samples were found positive by the assay. A quantitative, fast, and easy-to-handle diagnostic approach such as the MOMP-based real-time PCR described here might improve the detection of C. trachomatis infection.
Intensive pyrethroid use in insect control has led to resistance buildup among various pests. One alternative to battle this problem envisions the combined use of synergistically acting insecticidal compounds. Pyrethroids, scorpion alpha- and beta-toxins, and brevetoxins bind to distinct receptor sites on voltage-gated sodium channels (NaChs) and modify their function. The binding affinity of scorpion alpha-toxins to locust, but not rat-brain NaChs, is allosterically increased by pyrethroids and by brevetoxin-1. Brevetoxin-1 also increases the binding of an excitatory beta-toxin to insect NaChs. These results reveal differences between insect and mammalian NaChs and may be exploited in new strategies of insect control.
A new scorpionate borate ligand K[HB(7-azain)3](1, 7-azain = 7-azaindolyl) has been obtained from the reaction of KBH4 with excess 7-azaindole. The scorpionate ligand 1 was found to be able to form complexes with Zn(II) and Cu(I) ions. Complex 2 with the formula [BH(7-azain)3](ZnCl) has been obtained from the reaction of ZnCl2 with 1. Complex 3 with the formula [BH(7-azain)3][Cu(PPh3)] has been obtained from the reaction of [Cu(PPh3)2(CH3CN)2][BF4] with . The crystal structures of 1-3 have been determined by single-crystal X-ray diffraction analyses which revealed that has a dimeric structure linked together by two K+ ions, 2 has a symmetric tripodal structure with all three 7-azaindolyl groups being coordinated to the Zn(II) center, and 3 has an asymmetric structure with two of the 7-azaindolyl groups being coordinated to the Cu(I) center and the third 7-azaindolyl group uncoordinated. Variable temperature 1H NMR experiments established that 3 is highly dynamic in solution involving a rapid exchange between the coordinated and the non-coordinated 7-azaindolyl groups. All three compounds display blue emission in the solid state at ambient temperature. However, in solution at ambient temperature, compounds 1 and 2 display bright blue emission while compound 3 has no emission at all. At 77 K, solutions of all three compounds display blue-green phosphorescent emission with a long decay lifetime (> 2 ms).
An approach to obtain new active proteins is the incorporation of all or a part of a well defined active site onto a natural structure acting as a structural scaffold. According to this strategy we tentatively engineered a new curaremimetic molecule by transferring the functional central loop of a snake toxin, sequence 26-37, sandwiched between two hairpins, onto the structurally similar beta-hairpin of the scorpion toxin charybdotoxin, stabilized by a short helix. The resulting chimeric molecule, only 31 amino acids long, was produced by solid phase synthesis, refolded, and purified to homogeneity. As shown by structural analysis performed by CD and NMR spectroscopy, the chimera maintained the expected alpha/beta fold characteristic of scorpion toxins and presented a remarkable structural stability. The chimera competitively displaces the snake curaremimetic toxin alpha from the acetylcholine receptor at 10(-5) M concentrations. Antibodies, elicited in rabbits against the chimera, recognize the parent snake toxin and prevent its binding to the acetylcholine receptor, thus neutralizing its toxic function. All these data demonstrate that the strategy of active site transfer to the charybdotoxin scaffold has general applications in the engineering of novel ligands for membrane receptors and in vaccine design.
The iridescent layer in the corneal stroma of the scorpion fish, Taurulus (Cottus) bubalis (Scorpaeniformes), is composed of alternating thin lamellae of normal stroma containing collagen fibrils and lamellae of an amorphous dense-staining material. 2. Iridescence is lost after conventional resin embedding procedures, but is retained after embedding in urea-glutaraldehyde polymer. 3. The retention of iridescence and the absence of gross thickness changes during embedding in urea-glutaraldehyde polymer are an indication that the fine structure of the cornea is less altered than by conventional resin embedding. 4. It is believed that in life the collagen fibrils in the cornea of the scorpion fish and the cornea of the frog and rabbit are slightly larger and much more closely packed than is revealed by conventional resin-embedded sections.
Two major genotypic assemblages of Giardia lamblia infect humans; the epidemiologic significance of this phenomenon is poorly understood. We developed a single-vessel multiplex real-time PCR (qPCR) assay that genotypes Giardia infections into assemblages A and/or B directly from fecal samples. The assay utilized Scorpion probes that combined genotype-specific primers and probes for the 18S rRNA gene into the same molecule. The protocol was capable of detecting as few as 20 trophozoites per PCR on fecal DNA isolated using a commercial method or 1.25 trophozoites per PCR on fecal DNA isolated using a G. lamblia-specific oligonucleotide capture technique. The assay was specific for fecal specimens, with no amplification of the discordant genotype with the opposite Scorpion probe. When 97 clinical specimens from Bangladesh were used, the multiplex PCR assay detected 95% (21 of 22) of Giardia microscopy-positive specimens and 18% (13 of 74) of microscopy-negative specimens. Microscopy-negative and qPCR-positive specimens had higher average cycle threshold values than microscopy-positive and qPCR-positive specimens, suggesting that they represented true low-burden infections. Most (32 of 35) infections were assemblage B infections. This single-reaction multiplex qPCR assay distinguishes assemblage A Giardia infections from assemblage B infections directly on fecal samples and may aid epidemiologic investigation.
"Scorpion fish" is a nickname given by fishermen to members of the Trachinidae family as a result of their unusual stinging mechanism. These fish are found throughout the eastern Atlantic region from the North Sea through the Mediterranean and Black Seas and along the western coast of Northern and Central Africa. They are characterised by poisonous glands located at the base and sides of the spines of their anterior back fin and at the base of a spine located on the gill cover. Because of the unusual location of the glands, fishermen handling these fish frequently suffer local injuries. A case of necrosis of the tip of the middle finger after a "scorpion fish" sting is described.
90 min hypoxia (50% initial saturation) does not change the level of glucose-6-phosphate dehydrogenase activity in liver and brain of the red mullet. It is shown, that existence of the sea scorpion in environmental with low oxygen concentration (15% initial saturation) results in the increasing in this enzyme activity for 68% (p < 0.05). The rise of h values for NADP in 1.2-1.4 times and substrate-binding ability in 1.5-3 times are found for glucose-6-phosphate dehydrogenase from sea scorpion liver under hypoxia.
The total mRNA was prepared and purified from the venom gland of scorpion Buthus martensii Karsch (BmK). The cDNA library of this venom gland was then constructed using reverse transcription. Two cDNAs encoding the anti-mammalian neurotoxins, named as BmK M1 and BmK M9, were selectively amplified by PCR and sequenced. Both have open reading frames of 252 bp encoding 84 residues of the toxin precursors, including a 19 amino acid signal peptide, the mature toxin with 64 residues, and an additional Arg tail at the carboxyl-terminus which was removed during post-protein processing. The deduced amino acid sequence of BmK M1 was completely identical with the known sequence of the natural toxin BmK M4, whereas the other BmK M9 shared a high homology with the natural toxin BmK M4, differing only in two residues. The cDNA of BmK M1 showed 87.2% homology with that of the African scorpion Lqh alphaIT.
A total of 3866 patients stung by Tityus serrulatus scorpion was admitted to Hospital João XXIII, in Belo Horizonte, Brazil, over a 16-year period (an average of 241 cases per year). Of these, 73% were adults and 27% were children aged less than 14 years. The moderate or benign cases were treated with symptomatic measures and/or i.v. antivenom, whereas 168 severely envenomed children were treated in the Intensive Care Unit. Lung oedema was unilateral in several cases, with the presence of air bronchograms and a peripheral distribution, suggesting that a noncardiogenic factor is also involved in the genesis of lung oedema. The treatment consisted of symptomatic measures, support of vital functions and i.v. antivenom. The mortality was 1% among children and 0.28% for the total number of patients.
In Mexico, scorpionism is an endemic public health problem. The exact number of human accidents is unknown, but partial statistics suggests numbers close to 200,000 per year. The documented number of fatality cases is in the order of 310 people per year. We currently use horse antiserum in patients who show a clear picture of intoxication. Our personal experience in treating 38,068 people, from which over 20,000 received serotherapy, shows that the antiserum is very effective, in that none of the patients died.