{"title":"Toxins of the Helicobacter Genus and Their Roles in Pathogenesis","authors":"S. Hynes, T. Wadström","doi":"10.1081/TXR-120030646","DOIUrl":"https://doi.org/10.1081/TXR-120030646","url":null,"abstract":"In the 20 years since the discovery of Helicobacter pylori the number of formally described Helicobacter spp. has increased dramatically. The majority of species in the genus have been associated with some form of pathology. Similar to other Gram‐negative bacteria, all helicobacters have lipopolysaccharides or endotoxins in the outer leaflet of their outer membrane which is an important modulator of the immune system. H. pylori endotoxin has a number of roles in the pathogenesis of the bacterium. Its relatively low biological and immunological activity and molecular mimicry may contribute to the chronic nature of infection through avoidance of host defence mechanisms and adhesion. In addition to endotoxins, various helicobacters also secrete distinct exotoxins capable of host cell damage. H. pylori has been shown to possess a cytotoxin capable of inducing vacuoles in epithelial cells termed vacuolating cytotoxin or VacA. Although VacA has a number of roles in the pathogenesis of H. pylori its use as a predictor of clinical outcome has yet to be established. In addition, similar to the closely related Campylobacter jejuni, a number of enterohepatic helicobacters express a cytolethal distending toxin capable of inducing severe cell damage in vivo and in vitro. Both endotoxins and exotoxins may play a combined role in the pathogenesis of Helicobacter spp. Both toxin types have been identified as being present on outer membrane vesicles shed by H. pylori which may act as antigen delivery vehicles and contribute to pathogenesis.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"5 4 1","pages":"1 - 35"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78235172","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":"Biological Control of Aflatoxin Contamination of Crops","authors":"J. Dorner","doi":"10.1081/TXR-200027877","DOIUrl":"https://doi.org/10.1081/TXR-200027877","url":null,"abstract":"Aflatoxin contamination of crops compromises the safety of food and feed supplies and causes significant economic losses each year. Of the many research approaches being studied to reduce and, ultimately, eliminate aflatoxin contamination, biological control is one of the more promising, particularly for the near‐term. Numerous organisms have been tested for biological control of aflatoxin contamination including bacteria, yeasts, and nontoxigenic strains of the causal organisms, Aspergillus flavus and A. parasiticus. Most of the field successes to date have been achieved by applying certain nontoxigenic strains of A. flavus and A. parasiticus to soil of susceptible crops, such as peanuts, cotton, and corn. The applied strains occupy the same niche as the naturally occurring toxigenic strains and competitively exclude them when crops are susceptible to infection. Various formulations have been used to apply the nontoxigenic strains to soil, but the most effective methods have been to combine the desired strain with a carrier/substrate, such as a small grain. This was done either by minimally growing the desired strain on sterilized grain or by coating the surface of the grain with conidia of the strain. After application to the field and uptake of moisture, the fungus completely colonizes the grain, and abundant sporulation provides inoculum levels sufficient to achieve a competitive advantage for the nontoxigenic strain. In several years of field studies, particularly with peanuts and cotton, significant reductions in aflatoxin contamination in the range of 70–90% have been achieved consistently. Two separate products have recently received EPA registration as biopesticides to control aflatoxin contamination in cotton (AF36) and peanuts (afla‐guard®).","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"11 1","pages":"425 - 450"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91132825","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":"A Review of the Hematologic Effects of Green Pit Viper Venom","authors":"V. Wiwanitkit","doi":"10.1081/TXR-120030649","DOIUrl":"https://doi.org/10.1081/TXR-120030649","url":null,"abstract":"Green pit viper is an endemic venomous pit viper. After green pit viper bites, thrombocytopenia and increased fibrinolytic activity were observed in addition to defibrination. Hypofibrinogenemia with normal levels of the other clotting factors was observed. In addition, thrombocytopenia, which resulted from platelet aggregating activity of the venom has been described. These pathological effects act synergistically to cause bleeding in the victims. Clinical features of these venomous snakebites varies from asymptomatic to fatal bleeding. Reports concerning the hematologic effects of green pit viper are summarized in this review.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"5 1","pages":"105 - 110"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84192810","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":"Aflatoxins in Maize: A Mexican Perspective","authors":"J. Plasencia","doi":"10.1081/TXR-200027809","DOIUrl":"https://doi.org/10.1081/TXR-200027809","url":null,"abstract":"Aflatoxins are carcinogenic metabolites produced by Aspergillus flavus, a fungal pathogen that infects maize both in the field and during storage. Mexico is the center of origin of maize and its production in most parts in the country is characterized by the employment of a wide diversity of open‐pollinated genotypes adapted to certain environments. In most regions, maize is produced under rain fed conditions with low fertilizer and pesticide input and consequent low yields, probably fostering A. flavus infection in drought‐stressed plants. In addition, poor pest control increases insect damage, facilitating fungal infection and aflatoxin contamination. Ideally, management of aflatoxin contamination should begin with the employment of resistant genotypes as has been demonstrated by several U.S. breeding programs. However, in Mexico the wide genetic diversity of maize has not been fully exploited to identify resistance to aflatoxin contamination in breeding programs, thus impeding the reduction of aflatoxin levels in the field. Additional complications come from the fact that transgenic maize expressing insecticidal protein or any other trait to reduce aflatoxin is not viable in Mexico due to a government prohibition on the use of genetically modified maize. Maize is a staple crop in Mexico with high consumption in forms such as tortillas; thus, aflatoxin contamination is a significant threat to human health. Although aflatoxins are partially destroyed during the alkaline cooking procedure (called nixtamalization) to prepare tortillas, residual levels of aflatoxins might be considerable. Although important research has been conducted in several aspects of aflatoxin contamination of maize by universities, agricultural centers, and some government agencies, a full mycotoxin research program is needed in Mexico to ascertain the extents of aflatoxin contamination in different parts of the country and to develop economically viable technology to reduce aflatoxin exposure.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"8 1","pages":"155 - 177"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81867262","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":"Snake Venom Neurotoxins: Pharmacological Classification","authors":"S. Gawade","doi":"10.1081/TXR-120030647","DOIUrl":"https://doi.org/10.1081/TXR-120030647","url":null,"abstract":"Neurotoxic proteins isolated from various snake venoms, because of their high affinity for a particular target site are used extensively as pharmacological tools to gain insights into the function of the nervous system. The potency of these molecules lies in their affinities towards the biomolecules involved in the functioning of neuromuscular transmission. Neuromuscular and pathophysiological effects of neurotoxic proteins result from their interaction with various microcompartments based on their similarities in mass and conformation to the types of amino acids and disulfide bridges in the normal ligands. Snake venom toxins can be broadly classified depending on whether their site of action is at the skeletal neuromuscular junction, or at sites other than the skeletal neuromuscular junction. Skeletal neuromuscular junction‐specific neurotoxins include the following: postsynaptic toxins, presynaptic toxins, presynaptic toxins with musculotropic or myonecrotic actions, presynaptic and postsynaptic, presynaptic and postsynaptic toxins with musculotropic or myonecrotic actions, myotoxic and antiAChE neurotoxins, etc. Snake venom neurotoxins with affinities selective to the sites other than the skeletal NMJ were categorised as non‐skeletal neuromuscular junction snake venom neurotoxins and they include toxins with affinity for muscarinic and neuronal receptors; toxins with affinity for K+ and Ca2 + ion channels, toxins with affinity for enzymes and muscle elements, centrally‐acting neurotoxins, peptide neurotoxin and miscellaneous neurotoxins. There is an additional miscellaneous class of snake venom neurotoxins that includes weak neurotoxin, muscarinic toxin‐like proteins and vipoxin. The toxic mechanisms of well‐studied snake venom neurotoxins and their sites of action underlying neurotoxicity are discussed in this review, and they form the basis for classification of snake venom neurotoxins.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"33 1","pages":"37 - 96"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81385453","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":"N‐Fatty Acylation of Hydrolyzed Fumonisin B1, But Not of Intact Fumonisin B1, Strongly Enhances In Vitro Mammalian Toxicity","authors":"M. Abou‐Karam, H. Abbas, W. Shier","doi":"10.1081/TXR-120030651","DOIUrl":"https://doi.org/10.1081/TXR-120030651","url":null,"abstract":"Fumonisin B1 (FB1) is the most abundant of a series of sphingosine‐analog mycotoxins produced by Fusarium verticillioides, the major fungal contaminant of stored corn (maize) world‐wide. Fumonisins were originally isolated as environmental tumor promoters, and they remain a concern because they are frequent contaminants of corn‐derived food products intended for direct human consumption. FB1 inhibits ceramide synthase, which may account for its acute toxic effects, but understanding of its tumor promotion mechanism has been limited by the general lack of understanding in the field. There is no evidence for functional metabolism of fumonisins in mammals, but abiogenic conversions during food processing are a concern because some known conversion products retain biological activity, including hydrolyzed FB1 (HFB1). HFB1, formed by alkaline removal of FB1 side chains, is a frequent contaminant of lime‐treated corn products such as tortillas and tortilla chips. Humpf et al. (J. Biol. Chem., 273, 19060, 1998) observed that HFB1 not only inhibits ceramide synthase, but it is converted to a ceramide analog with about ten times the in vitro mammalian toxicity of intact FB1. In the present study we have confirmed this observation by preparing a series of ceramide analogs of HFB1 with varying fatty acid chain lengths and degree of unsaturation. Optimal in vitro mammalian toxicity was observed with fatty acid chain lengths of 10–14 carbons. However, ceramide analogs of HFB1 were not phytotoxic in vitro, and ceramide analogs of FB1 were not toxic in either mammalian or plant in vitro bioassays.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"1995 1","pages":"123 - 151"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89686063","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":"Cultural Methods for Aflatoxin Detection","authors":"H. Abbas, W. Shier, B. Horn, M. Weaver","doi":"10.1081/TXR-200027854","DOIUrl":"https://doi.org/10.1081/TXR-200027854","url":null,"abstract":"Aflatoxins present important food safely problems in both developed and developing countries. Contamination is monitored in developed countries using enzyme‐linked immunusorbent assay (ELISA)‐ and high‐performance liquid chromatography (HPLC)‐based assays, both of which may be too expensive for routine use in many developing countries. There is a need for inexpensive alternative approaches to detect aflatoxins in lots of foods and feeds. Reviewed here are culture‐based methods that determine if a sample is contaminated with aflatoxigenic fungi. These approaches include 1) blue fluorescence of aflatoxin B1, particularly when enhanced by including β‐cyclodextrin in the culture medium, 2) yellow pigment production, and 3) color change on exposure to ammonium hydroxide vapor. The presence of aflatoxin B1 can be detected by its blue fluorescence, which is enhanced when the toxin complexes with the hydrophobic pocket of β‐cyclodextrin. The yellow pigment and ammonium hydroxide vapor tests are based on the production of yellow anthraquinone biosynthetic intermediates in the aflatoxin pathway. These compounds act as pH indicator dyes, which are more visible when they have turned red at alkaline pH. Because these tests are based on two different mechanisms, it has been possible to combine them into a single test. In a study of 517 A. flavus isolates from the Mississippi Delta, the combined assay reduced false positives for aflatoxigenicity to 0%, and false negatives to 7%. The increased predictive power of the combined cultural assay may enable its use for inexpensively identifying potential aflatoxin contamination in feeds and foods.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"6 1","pages":"295 - 315"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83213664","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":"Worldwide Regulations on Aflatoxins—The Situation in 2002","authors":"H. V. van Egmond, M. A. Jonker","doi":"10.1081/TXR-200027844","DOIUrl":"https://doi.org/10.1081/TXR-200027844","url":null,"abstract":"Regulations have been established in many countries to protect the consumer from the harmful effects of mycotoxins. Current regulations mostly concern the aflatoxins, but regulations for other mycotoxins are now rapidly developing. Various factors play a role in the decision‐making process of setting limits for mycotoxins. These include scientific factors such as the availability of toxicological data and survey data, knowledge about the distribution of mycotoxins in commodities, and analytical methodology. Economical and political factors such as commercial interests and sufficiency of food supply have their impact as well. International inquiries on existing mycotoxin legislation in foodstuffs and animal feedstuffs have been carried out several times in the last two decades, yielding details about tolerances, legal bases, responsible authorities, and official protocols of analysis and sampling. Most of these surveys were conducted for the Food and Agricultural Organization (FAO) of the United Nations. The most recent survey was carried out in 2002 and is in fact still in the state of data processing. Nevertheless, some early (generalized) observations can be made about the development of legislation for aflatoxins in food and feed. The 2002 survey showed that about 100 countries now have specific regulations for aflatoxins in various foodstuffs, dairy products, and animal feeds. This is an increase of approximately 30% compared to the previous inquiry of 1995. The total population in these “aflatoxin‐regulated” countries represents 90% of the world's inhabitants. The survey also showed that aflatoxin regulations are becoming more diverse and detailed in relation to the commodities, and now include newer requirements regarding official procedures for sampling and analytical methodology. There is a slight tendency toward lower limits while, at the same time, some free trade zones (EU, MERCOSUR, Australia/New Zealand) have harmonized their limits and regulations for aflatoxins. Nevertheless, the regulatory requirements remain substantially different among the many countries.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"65 1","pages":"273 - 293"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90275424","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":"Aflatoxin and Food Safety: Recent South American Perspectives","authors":"V. Scussel","doi":"10.1081/TXR-200027813","DOIUrl":"https://doi.org/10.1081/TXR-200027813","url":null,"abstract":"South America (SA) is predominantly a tropical and subtropical continent and provides environmental conditions favorable for fungus growth on food crops, especially the species Aspergillus flavus and A. parasiticus. Depending on the grain and weather conditions in certain regions of SA, high levels of aflatoxins (AFLs) can be produced during harvesting or storage. That is a real problem in most of the continent. South American economies rely upon government policies to address issues of food safety. As expected, the exporting countries must comply with the standards and regulations that are implemented by the importing country. Thus, the highest quality and safest commodity food products are sold internationally. Conversely, food for internal consumption does not meet the same high quality standards compared with exports. Some SA governments have established food safety guidelines and regulations for AFL control in national food supplies. Research is currently being conducted to determine the levels of naturally occurring AFLs in a range of locally processed foods. These countries include: Brazil, Argentina, Colombia, Venezuela, and Uruguay, the main grain exporting countries in SA. Most contaminated food commodities in SA include peanut and peanut products, followed by corn. The regions most affected by AFL contamination in SA include mainly the peanut‐producing countries of northern SA as well as Brazil, Argentina, Uruguay, and Paraguay. Aflatoxin contamination of feeds and foodstuffs seems greater in Colombia and Ecuador. On the other hand, AFLs in corn is high in Venezuela. This review summarizes work published on AFLs throughout the previous decade. While most of the research has been performed in Brazil, Argentina, and Uruguay, other SA countries including Colombia and Venezuela also have played an important role in AFL research. Conversely, few studies on AFLs have been performed in Bolivia, Chile, Ecuador, and Peru, and no studies have been done in French Guyana, Guyana, Paraguay, and Suriname. There is a lack of data on the SA population exposure to AFLs, either using biomarkers or by evaluating the incidence of hepatocellular carcinoma (HCC) and its relation to AFLs in SA diets.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"27 1","pages":"179 - 216"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90324530","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":"Epidemiology of Aflatoxin Exposure and Human Liver Cancer","authors":"Jia-Sheng Wang, Lili Tang","doi":"10.1081/TXR-200027834","DOIUrl":"https://doi.org/10.1081/TXR-200027834","url":null,"abstract":"Aflatoxins, especially aflatoxin B1, are potent hepatocarcinogens that induce liver tumors in many species of animals, including rodents, nonhuman primates, and fish. Human primary liver cancer, mainly hepatocellular carcinoma, is one of the most common diseases in Asia, Africa, and in populations of Asian‐ and Hispanic‐Americans. Over the past 40 years there have been extensive efforts to investigate the association between aflatoxin exposure and human liver cancer. These studies have been hindered in earlier years by the lack of adequate biomarkers and dosimetry data on aflatoxin intake, excretion, and metabolism in people, as well as by the general poor quality of world‐wide cancer morbidity and mortality statistics. Many studies carried out in the past decade have incorporated the molecular analysis of the cancer gene targets and aflatoxin‐specific biomarkers, which have spurred efforts to assess aflatoxin exposure and human liver cancer risks. These molecular epidemiological studies eventually led to the reclassification of naturally occurring aflatoxins to a Group I human carcinogen by the International Agency for Research on Cancer in 1993, and the evaluation was reaffirmed in 2002. Current research in the field mainly focuses on studying interactions between aflatoxins and viral infections (hepatitis B/C viruses) and preventions of both aflatoxin exposure and viral infections.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":"45 1","pages":"249 - 271"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82196737","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}