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Toxins, Volume 4, Issue 9 (September 2012), Pages 633-767

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Research

Jump to: Review, Other

Open AccessArticle Simultaneous Detection of Ricin and Abrin DNA by Real-Time PCR (qPCR)
Toxins 2012, 4(9), 633-642; doi:10.3390/toxins4090633
Received: 14 July 2012 / Revised: 14 August 2012 / Accepted: 16 August 2012 / Published: 31 August 2012
Cited by 7 | PDF Full-text (2701 KB) | HTML Full-text | XML Full-text
Abstract
Ricin and abrin are two of the most potent plant toxins known and may be easily obtained in high yield from the seeds using rather simple technology. As a result, both toxins are potent and available toxins for criminal or terrorist acts. However,
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Ricin and abrin are two of the most potent plant toxins known and may be easily obtained in high yield from the seeds using rather simple technology. As a result, both toxins are potent and available toxins for criminal or terrorist acts. However, as the production of highly purified ricin or abrin requires sophisticated equipment and knowledge, it may be more likely that crude extracts would be used by non-governmental perpetrators. Remaining plant-specific nucleic acids in these extracts allow the application of a real-time PCR (qPCR) assay for the detection and identification of abrin or ricin genomic material. Therefore, we have developed a duplex real-time PCR assays for simultaneous detection of ricin and abrin DNA based on the OmniMix HS bead PCR reagent mixture. Novel primers and hybridization probes were designed for detection on a SmartCycler instrument by using 5′-nuclease technology. The assay was thoroughly optimized and validated in terms of analytical sensitivity. Evaluation of the assay sensitivity by probit analysis demonstrated a 95% probability of detection at 3 genomes per reaction for ricin DNA and 1.2 genomes per reaction for abrin DNA. The suitability of the assays was exemplified by detection of ricin and abrin contaminations in a food matrix. Full article
Open AccessArticle Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression
Toxins 2012, 4(9), 643-662; doi:10.3390/toxins4090643
Received: 20 June 2012 / Revised: 20 August 2012 / Accepted: 21 August 2012 / Published: 11 September 2012
Cited by 2 | PDF Full-text (897 KB) | HTML Full-text | XML Full-text
Abstract
Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the
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Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis. Full article
(This article belongs to the Special Issue Ochratoxins 2011-2012)
Figures

Open AccessArticle A Three-Year Survey on the Worldwide Occurrence of Mycotoxins in Feedstuffs and Feed
Toxins 2012, 4(9), 663-675; doi:10.3390/toxins4090663
Received: 31 July 2012 / Revised: 30 August 2012 / Accepted: 31 August 2012 / Published: 12 September 2012
Cited by 73 | PDF Full-text (170 KB) | HTML Full-text | XML Full-text
Abstract
Between January 2009 and December 2011, a total of 7049 corn, soybean/soybean meal, wheat, dried distillers grains with solubles (DDGS) and finished feed samples were analyzed for the occurrence of aflatoxins (Afla), zearalenone (ZEN), deoxynivalenol (DON), fumonisins (FUM) and ochratoxin A (OTA). Samples
[...] Read more.
Between January 2009 and December 2011, a total of 7049 corn, soybean/soybean meal, wheat, dried distillers grains with solubles (DDGS) and finished feed samples were analyzed for the occurrence of aflatoxins (Afla), zearalenone (ZEN), deoxynivalenol (DON), fumonisins (FUM) and ochratoxin A (OTA). Samples were sourced in the Americas, Europe and Asia. Afla, ZEN, DON, FUM and OTA were present respectively in 33%, 45%, 59% 64% and 28% of analyzed samples between 2009 and 2011. From the 23,781 mycotoxin analyzes performed, 81% were positive for at least one mycotoxin. Results of this survey are provided by calendar year, in order to potentially show different trends on mycotoxin occurrence in distinct years: by commodity type and within the same commodity, and by region, to potentially reveal differences in mycotoxin contamination in commodities sourced in diverse regions. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
Open AccessArticle Aspergillus Oxylipin Signaling and Quorum Sensing Pathways Depend on G Protein-Coupled Receptors
Toxins 2012, 4(9), 695-717; doi:10.3390/toxins4090695
Received: 3 August 2012 / Revised: 31 August 2012 / Accepted: 31 August 2012 / Published: 18 September 2012
Cited by 32 | PDF Full-text (4046 KB) | HTML Full-text | XML Full-text
Abstract
Oxylipins regulate Aspergillus development and mycotoxin production and are also involved in Aspergillus quorum sensing mechanisms. Despite extensive knowledge of how these oxylipins are synthesized and what processes they regulate, nothing is known about how these signals are detected and transmitted by the
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Oxylipins regulate Aspergillus development and mycotoxin production and are also involved in Aspergillus quorum sensing mechanisms. Despite extensive knowledge of how these oxylipins are synthesized and what processes they regulate, nothing is known about how these signals are detected and transmitted by the fungus. G protein-coupled receptors (GPCR) have been speculated to be involved as they are known oxylipin receptors in mammals, and many putative GPCRs have been identified in the Aspergilli. Here, we present evidence that oxylipins stimulate a burst in cAMP in A. nidulans, and that loss of an A. nidulans GPCR, gprD, prevents this cAMP accumulation. A. flavus undergoes an oxylipin-mediated developmental shift when grown at different densities, and this regulates spore, sclerotial and aflatoxin production. A. flavus encodes two putative GprD homologs, GprC and GprD, and we demonstrate here that they are required to transition to a high-density development state, as well as to respond to spent medium of a high-density culture. The finding of GPCRs that regulate production of survival structures (sclerotia), inoculum (spores) and aflatoxin holds promise for future development of anti-fungal therapeutics. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
Open AccessArticle Interaction between Shiga Toxin and Monoclonal Antibodies: Binding Characteristics and in Vitro Neutralizing Abilities
Toxins 2012, 4(9), 729-747; doi:10.3390/toxins4090729
Received: 28 August 2012 / Revised: 17 September 2012 / Accepted: 17 September 2012 / Published: 18 September 2012
Cited by 11 | PDF Full-text (1379 KB) | HTML Full-text | XML Full-text
Abstract
Monoclonal antibodies (MAbs) have been employed either for diagnosis or treatment of infections caused by different pathogens. Specifically for Shiga toxin-producing Escherichia coli (STEC), numerous immunoassays have been developed for STEC diagnosis, showing variability in sensitivity and specificity when evaluated by reference laboratories,
[...] Read more.
Monoclonal antibodies (MAbs) have been employed either for diagnosis or treatment of infections caused by different pathogens. Specifically for Shiga toxin-producing Escherichia coli (STEC), numerous immunoassays have been developed for STEC diagnosis, showing variability in sensitivity and specificity when evaluated by reference laboratories, and no therapy or vaccines are currently approved. Thus, the aim of this work was the characterization of the interaction between MAbs against Stx1 and Stx2 toxins and their neutralizing abilities to enable their use as tools for diagnosis and therapy. The selected clones designated 3E2 (anti-Stx1) and 2E11 (anti-Stx2) were classified as IgG1. 3E2 recognized the B subunit of Stx1 with an affinity constant of 2.5 × 10−10 M, detected as little as 6.2 ng of Stx1 and was stable up to 50 ºC. In contrast, 2E11 recognized the A subunit of Stx2, was stable up to 70 ºC, had a high dissociation constant of 6.1 × 10−10 M, and detected as little as 12.5 ng of Stx2. Neutralization tests showed that 160 ng of 3E2 MAb inhibited 80% of Stx1 activity and 500 µg 2E11 MAb were required for 60% inhibition of Stx2 activity. These MAb amounts reversed 25 to 80% of the cytotoxicity triggered by different STEC isolates. In conclusion, these MAbs show suitable characteristics for their use in STEC diagnosis and encourage future studies to investigate their protective efficacy. Full article
(This article belongs to the Special Issue Toxin-Antibody Interactions)

Review

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Open AccessReview Macrophage-Targeted Therapy: CD64-Based Immunotoxins for Treatment of Chronic Inflammatory Diseases
Toxins 2012, 4(9), 676-694; doi:10.3390/toxins4090676
Received: 16 August 2012 / Revised: 4 September 2012 / Accepted: 5 September 2012 / Published: 14 September 2012
Cited by 15 | PDF Full-text (506 KB) | HTML Full-text | XML Full-text
Abstract
Diseases caused by chronic inflammation (e.g., arthritis, multiple sclerosis and diabetic ulcers) are multicausal, thus making treatment difficult and inefficient. Due to the age-associated nature of most of these disorders and the demographic transition towards an overall older population, efficient therapeutic intervention strategies
[...] Read more.
Diseases caused by chronic inflammation (e.g., arthritis, multiple sclerosis and diabetic ulcers) are multicausal, thus making treatment difficult and inefficient. Due to the age-associated nature of most of these disorders and the demographic transition towards an overall older population, efficient therapeutic intervention strategies will need to be developed in the near future. Over the past decades, elimination of activated macrophages using CD64-targeting immunotoxins has proven to be a promising way of resolving inflammation in animal models. More recent data have shown that the M1-polarized population of activated macrophages in particular is critically involved in the chronic phase. We recapitulate the latest progress in the development of IT. These have advanced from full-length antibodies, chemically coupled to bacterial toxins, into single chain variants of antibodies, genetically fused with fully human enzymes. These improvements have increased the range of possible target diseases, which now include chronic inflammatory diseases. At present there are no therapeutic strategies focusing on macrophages to treat chronic disorders. In this review, we focus on the role of different polarized macrophages and the potential of CD64-based IT to intervene in the process of chronic inflammation. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
Open AccessReview The Biological Control of the Malaria Vector
Toxins 2012, 4(9), 748-767; doi:10.3390/toxins4090748
Received: 29 June 2012 / Revised: 29 August 2012 / Accepted: 3 September 2012 / Published: 19 September 2012
Cited by 15 | PDF Full-text (228 KB) | HTML Full-text | XML Full-text
Abstract
The call for malaria control, over the last century, marked a new epoch in the history of this disease. Many control strategies targeting either the Plasmodium parasite or the Anopheles vector were shown to be effective. Yet, the emergence of drug resistant parasites
[...] Read more.
The call for malaria control, over the last century, marked a new epoch in the history of this disease. Many control strategies targeting either the Plasmodium parasite or the Anopheles vector were shown to be effective. Yet, the emergence of drug resistant parasites and insecticide resistant mosquito strains, along with numerous health, environmental, and ecological side effects of many chemical agents, highlighted the need to develop alternative tools that either complement or substitute conventional malaria control approaches. The use of biological means is considered a fundamental part of the recently launched malaria eradication program and has so far shown promising results, although this approach is still in its infancy. This review presents an overview of the most promising biological control tools for malaria eradication, namely fungi, bacteria, larvivorous fish, parasites, viruses and nematodes. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)

Other

Jump to: Research, Review

Open AccessBrief Report Intranasal Rapamycin Rescues Mice from Staphylococcal Enterotoxin B-Induced Shock
Toxins 2012, 4(9), 718-728; doi:10.3390/toxins4090718
Received: 2 July 2012 / Revised: 6 August 2012 / Accepted: 13 August 2012 / Published: 18 September 2012
Cited by 6 | PDF Full-text (273 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcal enterotoxin B (SEB) and related exotoxins produced by Staphylococcus aureus are potent activators of the immune system and cause toxic shock in humans. Currently there is no effective treatment except for the use of intravenous immunoglobulins administered shortly after SEB exposure. Intranasal
[...] Read more.
Staphylococcal enterotoxin B (SEB) and related exotoxins produced by Staphylococcus aureus are potent activators of the immune system and cause toxic shock in humans. Currently there is no effective treatment except for the use of intravenous immunoglobulins administered shortly after SEB exposure. Intranasal SEB induces long-lasting lung injury which requires prolonged drug treatment. We investigated the effects of rapamycin, an immunosuppressive drug used to prevent graft rejection, by intranasal administration in a lethal mouse model of SEB-induced shock. The results show that intranasal rapamycin alone delivered as late as 17 h after SEB protected 100% of mice from lethal shock. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB. Intranasal rapamycin attenuated lung MCP-1, IL-2, IL-6, and IFNγ by 70%, 30%, 64%, and 68% respectively. Furthermore, short courses (three doses) of rapamycin were sufficient to block SEB-induced shock. Intranasal rapamycin represents a novel use of an immunosuppressant targeting directly to site of toxin exposure, reducing dosages needed and allowing a wider therapeutic window. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)

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