| 1. |
- Brown, Mark A., et al.
(författare)
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Detection of vitamin K-dependent proteins in venoms with a monoclonal antibody specific for gamma-carboxyglutamic acid.
- 2002
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Ingår i: Toxicon. - 0041-0101. ; 40:4, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Carboxyglutamic acid (Gla) is an unusual amino acid that is synthesized post-translationally from glutamate in a vitamin K-dependent reaction. The dicarboxylic side chain of Gla chelates Ca(2+), a property important for the biological activity of vitamin K-dependent proteins. To date, Gla-containing polypeptides have been identified in venom from two groups of organisms: elapid snakes, and snails of the genus Conus. In certain elapid snakes, a gamma-carboxylated coagulation factor Xa-like protein is a component of the venom whereas cone snails utilize Gla in a range of peptide neurotoxins. Using a monoclonal antibody that specifically recognizes Gla residues, venom samples from various organisms were screened by western blotting and immunofluorescence assays. Amino acid analyses were also performed on most samples. A survey of 21 snake species from 12 genera detected gamma-carboxylated polypeptides only in venom of snakes from the elapid subfamily Acanthophiinae. Gla-containing polypeptides were also observed in cone snail venom but not in venom or toxic salivary secretions from several other organisms. The Gla-specific antibody used here provides a simple immunochemical means to detect gamma-carboxylated polypeptides in venom and may allow new species to be identified that utilize Gla in the biosynthesis of toxic polypeptides.
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| 2. |
- Dahlmann, J, et al.
(författare)
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Different methods for toxin analysis in the cyanobacterium Nodularia spumigena (Cyanophyceae)
- 2001
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Ingår i: Toxicon. - 0041-0101. ; 39:8, s. 1183-1190
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The brackish water cyanobacterium Nodularia spumigena produce the hepatotoxic cyclic pentapeptide nodularin. Intoxications for both human as well as animal may arise when water reservoirs are contaminated with potentially toxic Nodularia species. Here, results of three independent methods for the determination of nodularin in different strains of N. spumigena are presented. The results obtained with a protein phosphatase assay and a HPLC/UV/MS method are compared with the results obtained with a bioluminescence assay, which is successfully introduced here for nodularin determination. Statistical evaluation of the three applied methods revealed a good comparability towards the detected toxin content. The methods were evaluated taking into consideration the parameters: handling, efficiency, sensitivity and selectivity. The detection limit in the protein phosphatase assay is highest (0.05 ng nodularin) and lowest (250 ng nodularin) in the bioluminescence assay— it was determined with 5 ng (MS) and 25 ng (UV) for the HPLC/UV/MS methods. The different selectivities and sensitivities are critically discussed and an analytical pathway for the determination of the biotoxin nodularin from Nodularia samples is proposed.
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| 7. |
- Jolkkonen, Mikael, et al.
(författare)
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Kinetic evidence for different mechanisms of interaction of black mamba toxins MT alpha and MT beta with muscarinic receptors
- 2001
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 39:2-3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- By studying the influence of two toxins from the black mamba Dendroaspis polylepis on the kinetics of [H-3]-N-methylscopolamine binding to muscarinic acetylcholine receptors from rat cerebral cortex, it was revealed that these toxins, MT alpha and MT beta, interact with the receptors via kinetically distinct mechanisms. MT beta bound to receptors in a one-step, readily reversible process with the dissociation constant K-d = 5.3 mu M. The binding mechanism of MT alpha was more complex, involving at least two consecutive steps. A fast receptor-toxin complex formation (K-T = 3.8 mu M) was followed by a slow process of isomerisation of this complex (k(i) = 1.8 x 10(-2) s(-1), half-time 39 s). A similar two-step interaction mechanism has been established for a related toxin, MT2 from the green mamba D. angusticeps (K-T = 1.4 mu M, k(i) = 8.3 x 10(-4) s(-1), half-time 840 s). The slow isomerisation process delays the effect of MT alpha and MT2, but increases their apparent potency compared to toxins unable to induce the isomerisation process.
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| 8. |
- Sundell, I.B., et al.
(författare)
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In vitro procoagulant and anticoagulant properties of Naja naja naja venom
- 2003
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 42:3, s. 239-247
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Tidskriftsartikel (refereegranskat)abstract
- Bites by the Indian cobra (Naja naja naja) are common in India and Sri Lanka because of its close association with humans. Cobra venoms are complex and contain several toxic components, including neurotoxins that cause post-synaptic neuromuscular blockade with respiratory paralysis and even death. Bites may also cause extensive local necrosis by mechanisms not fully elucidated. Although no significant coagulopathy has been reported, N.n. naja venom can form blood clots in vitro by activating prothrombin as demonstrated by thrombin-specific chromogenic substrate. Scanning electron microscopy demonstrates that the clots formed by venom lack the thin fibrin strands of normal blood clots formed by thromboplastin or glass contact. Rheometry shows that clots formed by venom have abnormally low elasticity over an extended period and then, as the platelets contract, a retarded and more feeble increase in elasticity. Purified N.n. naja venom PLA2 inhibits platelet aggregation in PRP and explains the decreased clot retraction and retarded and compromised elasticity build up. The present study shows that the PLA 2 and the prothrombin activator from N.n. naja venom have effects on haemostasis and blood clotting, although such effects are not observed systemically in envenomed humans. © 2003 Elsevier Ltd. All rights reserved.
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| 9. |
- Araujo, S. C. M., et al.
(författare)
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Use of geospatial analyses to address snakebite hotspots in mid-northern Brazil - A direction to health planning in shortfall biodiversity knowledge area
- 2022
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 213, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Knowing the distribution of venomous snakes of medical importance is essential to identify areas at risk for snakebites. Thus, we used an integrative approach based on the application of geographic distribution data of venomous snakes, species distribution modeling (SDM), spatial organization of snakebites, and information on human population density for mapping the potential distribution of snakes and identifying areas at risk of snakebites in the state of Maranhao (mid-northern Brazil). From a compiled database of venomous snake records deposited in biological collections and the literature, we predict the potential distribution of venomous snakes in Maranhao, a state whose diversity and geographic distribution of venomous snake species are poorly known. With this, we constructed potential distribution maps for each venomous snake species with at least one occurrence record within state boundaries, as well as generalized maps by family (Viperidae and Elapidae) and the total number of venomous snakes in Maranhao State. We also obtained data on the number of snakebites recorded in each municipality of Maranhao over a decade (2009-2019) and we ran a Generalized Linear Model to test for relationships between the number of venomous snakebites, the area of occurrence of snakes, and human population density. We obtained 1046 records of venomous snake species for Maranhao, represented by 17 viperid and elapid species. Most of the records were from Viperidae (mostly Bothrops atrox and B. marajoensis) and were concentrated mainly in the Amazon of the northern portion of the state. The models showed accurate predictive performance for all modeled species. The entire area of Maranhao exhibits environmental conditions for the occurrence of venomous snakes, with higher suitability indices in the northern region, in the Amazon rainforest. The number of snakebites was positively correlated with the interaction between high-risk areas (i.e., greater distribution of venomous snakes) and human population density. Our study is a pioneer in using species distribution modeling in mid-northern Brazil to address the scarcity of data on snakebite-causing species, directly contributing to the theme of neglected tropical diseases of the World Health Organization.
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| 10. |
- Bhattacharjee, Payel, 1984, et al.
(författare)
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Aristolochic acid and its derivatives as inhibitors of snake venom L-amino acid oxidase
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 138, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Snake venom L-amino acid oxidase (LAAO) exerts toxicity by inducing hemorrhage, pneumorrhagia, pulmonary edema, cardiac edema, liver cell necrosis etc. Being well conserved, inhibitors of the enzyme may be synthesized using the template of the substrate, substrate binding site and features of the catalytic site of the enzyme. Previous findings showed that aristolochic acid (AA), a major constituent of Aristolochia indica, inhibits Russell's viper venom LAAO enzyme activity since, AA interacts with DNA and causes genotoxicity, derivatives of this compound were synthesized by replacing the nitro group to reduce toxicity while retaining the inhibitory potency. The interactions of AA and its derivatives with LAAO were followed by inhibition kinetics and surface plasmon resonance. Similar interactions with DNA were followed by absorption spectroscopy and atomic force microscopy. LAAO-induced cytotoxicity was evaluated by generation of reactive oxygen species (ROS), cell viability assays, confocal and epifluorescence microscopy. The hydroxyl (AA-OH) and chloro (AA-C1) derivatives acted as inhibitors of LAAO but did not interact with DNA. The derivatives significantly reduced LAAO-induced ROS generation and cytotoxicity in human embryonic kidney (HER 293) and hepatoma (HepG2) cell lines. Confocal images indicated that AA, AA-OH and AA-Cl interfered with the binding of LAAO to the cell membrane. AA-OH and AA-CI significantly inhibited LAAO activity and reduced LAAO-induced cytotoxicity. (C) 2017 Elsevier Ltd. All rights reserved.
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