Journal of Toxicology-toxin Reviews最新文献

{"title":"Stonefish (Synanceia trachynis) Antivenom: In Vitro Efficacy and Clinical Use","authors":"J. Church, W. Hodgson","doi":"10.1081/TXR-120019021","DOIUrl":"https://doi.org/10.1081/TXR-120019021","url":null,"abstract":"Certain species of fish have long been recognised as venomous. Although venomous fish do not represent a substantial source of human mortality, they are responsible for a number of envenomations each year that are serious enough to warrant clinical treatment. To the author's knowledge, the only fish antivenom still commercially available is the stonefish antivenom produced by CSL Ltd. in Australia. This antivenom consists of the purified F(ab)2 fragment of equine IgG antibodies raised against the venom of Synanceia trachynis. The antivenom is cheap, and effective in neutralising all known clinical effects of serious S. trachynis envenomation. In addition, there is experimental evidence that stonefish antivenom neutralises the pharmacological effects of other fish venoms, particularly those of the lionfish (Pterois volitans) and the soldierfish (Gymnapistes marmoratus), as well as displaying cross‐reactivity with them in Western immuno‐blotting. The potential therefore exists for the use of stonefish antivenom in the treatment of severe envenomations by species of fish other than Synanceia spp.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82216845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Differential Display RT‐PCR and EST/Microarray Technologies to the Analysis of Gene Expression in Response to Drought Stress and Elimination of Aflatoxin Contamination in Corn and Peanut","authors":"Baozhu Guo, Jiujiang Yu†, C. Holbrook, R. D. Lee, R. Lynch","doi":"10.1081/TXR-120024095","DOIUrl":"https://doi.org/10.1081/TXR-120024095","url":null,"abstract":"Aflatoxin contamination in the field is known to be influenced by numerous factors. Drought and high temperatures are conducive to Aspergillus flavus infection and aflatoxin contamination. This article will review the application of new molecular tools to study host resistance to biotic and abiotic factors affecting preharvest aflatoxin contamination in corn and peanut. We will also summarize recent studies conducted in our laboratories to evaluate the relationship of drought tolerance and aflatoxin contamination, and discuss the progress in using genetic engineering approaches to control preharvest aflatoxin contamination. The application of molecular tools, such as proteomics, DD‐RT‐PCR (differential display reverse transcription‐polymerase chain reaction), expressed sequence tag (EST) and gene chip technology (macro/micro‐array) to study gene expression in response to drought stress, and genetic transformation, will be reviewed. We have used DD‐RT‐PCR to display genes expressed in peanut and corn grown under drought stress vs irrigation condition. A new program has been initiated to use EST/microarray technology to study the whole genome as influenced by drought stress in corn and peanut. We are also studying A. flavus ESTs to better understand the genetic control and regulation of toxin biosynthesis. Because of the complexity of the Aspergillus‐plant (corn and peanut) interactions, better understanding of the genetic mechanisms of resistance will be needed using both conventional and molecular breeding for crop improvement and control of preharvest aflatoxin contamination. Genetic improvement of crop resistance to drought stress is one component and will provide a good perspective on the efficacy of control strategy through genetic improvement.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77586552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studies Aimed at the Total Synthesis of Azadirachtin as an Insect Antifeedant","authors":"A. Murai*","doi":"10.1081/TXR-120026917","DOIUrl":"https://doi.org/10.1081/TXR-120026917","url":null,"abstract":"Efficient construction of the respective right and left segments of azadirachtin is described. Furthermore, studies on the connection between both the segments are also mentioned; the Ireland‐Claisen rearrangement of Li‐enolate of the modelled ester with dichlorodimethylsilane in toluene afforded the desired limonoid framework stereoselectively in good yield.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77831540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STRUCTURE AND FUNCTION OF α-BUNGAROTOXIN","authors":"L. Moise, H. Zeng, P. Caffery, R. Rogowski, E. Hawrot","doi":"10.1081/TXR-120014407","DOIUrl":"https://doi.org/10.1081/TXR-120014407","url":null,"abstract":"The long α-neurotoxin, α-Bungarotoxin (Bgtx), from the venom of the Taiwan banded krait, Bungarus multicinctus, is a high affinity competitive antagonist of skeletal muscle-type nicotinic acetylcholine receptors (nAChRs) and of certain homo-oligomeric neuronal nicotinic acetylcholine receptors. Bgtx has a long and illustrious record as a valuable tool for the identification, purification, and localization of skeletal muscle-type nAChRs. The structure and function of Bgtx is of special interest as Bgtx is the prototypical member of a large family of curaremimetic α-neurotoxins from the venoms of Elapidae and Hydrophidae snakes. Bgtx has been the focus of extensive studies aimed at discerning the structural basis for its high affinity interaction with nAChRs. Over the past year, our understanding has advanced significantly with the crystal structure of the acetylcholine-binding protein, AChBP, a nAChR extracellular domain homologue, and with structure determinations of Bgtx and its complexes with receptor-sequence-derived peptide fragments or affinity-selected peptide mimotopes. The heterologous expression of a recombinant Bgtx has facilitated site-directed mutagenesis as an additional approach towards elucidating the structure–function relationship. The results from structural and mutagenesis studies suggest that cation–π interactions play an important role in receptor recognition. Conformational plasticity at the end of the second finger in Bgtx may also be important for specificity and affinity. Finally, a new term, “pharmatope”, is proposed to designate the novel recombinant introduction of Bgtx binding sequences into proteins that are normally unrecognized by Bgtx. Such a “pharmatope” would be an invaluable pharmacological tool allowing experimental access to the multi-purpose derivatives of Bgtx.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74472765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLOSTRIDIAL NEUROTOXINS","authors":"C. Verastegui, G. Lalli, S. Bohnert, F. Meunier, G. Schiavo","doi":"10.1081/TXR-120014404","DOIUrl":"https://doi.org/10.1081/TXR-120014404","url":null,"abstract":"Tetanus (TeNT) and botulinum (BoNTs) neurotoxins are powerful toxins endowed with a specific zinc-endopeptidase activity. Targets of these neurotoxins have been identified as synaptic members of the SNARE proteins, which are involved in the exocytosis of neurotransmitters at the synapse. Despite this identical intracellular mechanism of action, TeNT and BoNTs target different neurons in vivo. After binding at the neuromuscular junction, BoNTs block neurotransmitter release at this site, whereas TeNT is retrogradely transported through motor neurons and inhibits exocytosis in inhibitory interneurons. Recently, several studies have reported the structure of these neurotoxins and clarified important aspects of the intoxication process. However, important questions on the mechanism responsible for the binding specificity and for the targeting of TeNT and BoNTs remain to be addressed. Once elucidated, this novel information would enables us to use CNTs more efficiently as therapeutic tools in neuronal disorders.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73035394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BIOCHEMISTRY AND PHARMACOLOGY OF COLUBRID SNAKE VENOMS","authors":"S. Mackessy","doi":"10.1081/TXR-120004741","DOIUrl":"https://doi.org/10.1081/TXR-120004741","url":null,"abstract":"The polyphyletic family Colubridae contains approximately two-thirds of the described species of advanced snakes, and nearly half of these (∼700 species) produce a venom in a specialized cephalic gland, the Duvernoy's gland. Biochemical and pharmacological information is lacking for venoms of most species, and modest detailed information on venom composition is available for only a few species which represent a potential health threat to humans. However, colubrid venoms represent a vast source of novel compounds, and some toxins, such as the 20–26 kD CRISP-related venom proteins (helveprins), have only recently been identified in both colubrid and elapid/viperid venoms. Difficulties associated with extraction have been addressed, and it is now possible to obtain venom sufficient for many analyses from even small species. There appears to be a greater number of venom components shared among the colubrids and the front-fanged snakes than has been previously noted, and it is probable that as analytical methods improve, more similarities will emerge. It is clear that colubrid venoms are homologous with front-fanged snake venoms, but overall composition as well as biological role(s) of colubrid venoms may be quite different. Metallo- and serine proteases have been identified in several colubrid venoms, and phospholipase A2 is a more frequent component than has been previously recognized. Venom phosphodiesterase, acetylcholinesterase and prothrombin activator activities occur in some venoms, and postsynaptic neurotoxins and myotoxins have been partially characterized for venoms from several species. Some venoms show high toxicity toward inbred mice, and others are toxic to birds and/or frogs only. Because many colubrids feed on non-mammalian prey, lethal toxicity toward mice is likely only relevant as a measure of potential risk posed to humans. Development of a non-mammalian vertebrate animal model would greatly facilitate systematic comparisons of the pharmacology of colubrid venoms and their components, and such a model would be more appropriate for evaluation of colubrid venom toxicity. Proteomics has the potential to increase our understanding of these venoms rapidly, but classical approaches to toxinology can also contribute tremendously to this understudied field. As more colubrid venoms are analyzed, new compounds unique to colubrid venoms will be identified, and this work in turn will lead to a better understanding of the evolution and biological significance of snake venoms and venom components.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81874923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COLUBRID ENVENOMATIONS IN THE UNITED STATES","authors":"D. Chiszar, Hobart M. Smith","doi":"10.1081/TXR-120004742","DOIUrl":"https://doi.org/10.1081/TXR-120004742","url":null,"abstract":"The literature concerned with colubrid envenomations in the United States is reviewed, including cases involving Americans who were envenomated by exotic snakes. Because exotic snakes have become readily available through the pet trade, it is essential for medical personnel to realize that snake-bite victims presenting themselves at North American hospitals may have been bitten by South American, Asian, African or European animals. Major themes emerging from this review are: 1) some colubrid envenomations have been serious, even life threatening, 2) many so-called envenomations might actually be allergic reactions, 3) extreme variability seems to characterize Duvernoy's secretions, intraspecifically as well as interspecifically, 4) even within the same individual, Duvernoy's secretion can vary in composition and action from time to time, and 5) we know little about the determinants of this variability, although a variety of hypotheses are available. Opportunities for research in this area are extensive. Likewise, we know little about the historical or current biological role(s) of Duvernoy's secretions, and once again there exists a plethora of hypotheses, only a few of which have been tested. We appear to be standing at the threshold of a new era of exciting empirical and theoretical discoveries, some of which may redefine the way we think about colubrid oral secretions.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74728911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THE STRUCTURE AND FUNCTION OF PARDAXIN","authors":"P. Lazarovici","doi":"10.1081/TXR-120014410","DOIUrl":"https://doi.org/10.1081/TXR-120014410","url":null,"abstract":"Pardaxins are polypeptide pore-forming neurotoxins that alter cell plasma membrane permeability by packaging of the hydrophobic, amphipathic α-helices and assembly in the plasma membrane in oligomeric, poorly selective channels. At subcytotoxic concentrations, these small lesions in the plasma membrane induce a sustained increase in intracellular calcium activation, stimulation of the arachidonic acid cascade and massive release of neurotransmitters. These crucial events are further amplified by cascades of cellular signaling, due to the release of local mediators (prostaglandins) and/or neurotransmitters (dopamine) and modifications of intracellular enzymes, ion channels and receptor activities. The end result is a lethal hit to the signal transduction machinery of the attacked cell, resulting in cell death. Elucidation of the neuronal signal transduction pathways affected by pardaxin could provide a new understanding of synaptic transmission and new targets for therapy of patients affected by neurotoxins.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87086977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STRUCTURE AND FUNCTION OF DIPHTHERIA TOXIN: FROM PATHOLOGY TO ENGINEERING","authors":"A. Chenal, P. Nizard, D. Gillet","doi":"10.1081/TXR-120014408","DOIUrl":"https://doi.org/10.1081/TXR-120014408","url":null,"abstract":"Among bacterial protein toxins with an intracellular target, diphtheria toxin is one of the most studied. Since the first publication of its crystal structure in 1992, tremendous progress has been made describing the molecular events involved in its toxicity. However, the precise mechanism of translocation is not fully understood yet. The diphtheria toxin contains three structural domains, each carrying a distinct biological function implicated in the intoxication of the cell. The receptor-binding domain mediates the recognition of a specific receptor on the surface of targeted cells. This binding event allows the internalization of the toxin by the cells and its routing towards acidic intracellular compartments. The translocation (or transmembrane) domain, reacting to the low pH, penetrates the membrane and assists the transport of the catalytic domain through this membrane into the cytoplasm. There, the catalytic domain transfers an ADP-ribose from cytosolic NAD to its substrate, the elongation factor 2. This activity blocks the synthesis of cellular proteins, leading to cell death. All three domains of the diphtheria toxin, isolated or combined with other proteins, are now exploited for their biological properties to design new biotechnological tools and new therapeutics.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84744739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BITES AND ENVENOMATIONS BY COLUBRID SNAKES IN MEXICO AND CENTRAL AMERICA","authors":"J. Gutiérrez, M. Sasa","doi":"10.1081/TXR-120004743","DOIUrl":"https://doi.org/10.1081/TXR-120004743","url":null,"abstract":"Information on bites by snakes of the family Colubridae in Mexico and Central America is reviewed. Little is known of the biochemistry and pharmacology of the Duvernoy gland secretion (venom) of colubrids from this region, although some reports describe proteolytic, phosphodiesterase, phospholipase A2 and hemorrhagic activities. A search of published reports and an effort to obtain reliable unpublished information on colubrid snake bites in the region documented cases inflicted by species of the genera Conophis, Coniophanes, Crisantophis, Erythrolamprus, Pliocercus, Oxybelis and Dryadophis (=Mastigodryas). The following general pattern emerges from the analysis of these cases: 1) Bites occurred mainly in hands and fingers on people that frequently manipulate colubrids, i.e. herpetologists, herpetoculturists and people that take care of these snakes at museums, exhibits or zoos; and 2) In most cases, only mild local effects were described, i.e. pain, swelling and, in few cases, ecchymosis. In only one case by Erythrolamprus bizonus there was ecchymosis beyond the bitten region, whereas persistent bleeding at the bite site was reported in a Conophis lineatus case. No systemic alterations were described in any of the cases. Management of colubrid bites in Mexico and Central America includes cleaning and disinfection of the bitten area, together with administration of tetanus toxoid. In the case of local infection, antibiotics are administered. There is no experimental or clinical evidence supporting the use of Crotalinae antivenoms in these bites. Despite the lack of systemic alterations in the cases described, caution should be exercised when manipulating these snakes, and bitten people should be closely observed for the potential development of bleeding and coagulopathies, since these effects have been described in bites by colubrid snakes from other regions of the world.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77136098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}