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Toxins, Volume 4, Issue 11 (November 2012), Pages 956-1414

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Research

Jump to: Review

Open AccessArticle Botulinum Toxin A for Oral Cavity Cancer Patients: In Microsurgical Patients BTX Injections in Major Salivary Glands Temporarily Reduce Salivary Production and the Risk of Local Complications Related to Saliva Stagnation
Toxins 2012, 4(11), 956-961; doi:10.3390/toxins4110956
Received: 31 August 2012 / Revised: 25 September 2012 / Accepted: 18 October 2012 / Published: 24 October 2012
Cited by 8 | PDF Full-text (179 KB) | HTML Full-text | XML Full-text
Abstract
In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection) and to reconstruct the affected area by means of free flaps. The saliva
[...] Read more.
In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection) and to reconstruct the affected area by means of free flaps. The saliva stagnation in the post-operative period is a risk factor with regard to local complications. Minor complications related to saliva stagnation (such as tissue maceration and wound dehiscence) could become major complications compromising the surgery or the reconstructive outcome. In fact the formation of oro-cutaneous fistula may cause infection, failure of the free flap, or the patient’s death with carotid blow-out syndrome. Botulinum injections in the major salivary glands, four days before surgery, temporarily reduces salivation during the healing stage and thus could reduce the incidence of saliva-related complications. Forty three patients with oral cancer were treated with botulinum toxin A. The saliva quantitative measurement and the sialoscintigraphy were performed before and after infiltrations of botulinum toxin in the major salivary glands. In all cases there was a considerable, but temporary, reduction of salivary secretion. A lower rate of local complications was observed in the post-operative period. The salivary production returned to normal within two months, with minimal side effects and discomfort for the patients. The temporary inhibition of salivary secretion in the post-operative period could enable a reduction in saliva-related local complications, in the incidence of oro-cutaneous fistulas, and improve the outcome of the surgery as well as the quality of residual life in these patients. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)
Open AccessArticle Toxigenic Potential of Aspergillus Species Occurring on Maize Kernels from Two Agro-Ecological Zones in Kenya
Toxins 2012, 4(11), 991-1007; doi:10.3390/toxins4110991
Received: 24 July 2012 / Revised: 17 October 2012 / Accepted: 17 October 2012 / Published: 25 October 2012
Cited by 12 | PDF Full-text (863 KB) | HTML Full-text | XML Full-text
Abstract
Two agro-ecological zones in Kenya were selected to compare the distribution in maize of Aspergillus spp. and their toxigenicity. These were Nandi County, which is the main maize growing region in the country but where no human aflatoxicoses have been reported, and Makueni
[...] Read more.
Two agro-ecological zones in Kenya were selected to compare the distribution in maize of Aspergillus spp. and their toxigenicity. These were Nandi County, which is the main maize growing region in the country but where no human aflatoxicoses have been reported, and Makueni County where most of the aflatoxicosis cases have occurred. Two hundred and fifty-five households were sampled in Nandi and 258 in Makueni, and Aspergillus was isolated from maize. Aspergillus flavus and A. parasiticus isolates were tested for the presence of aflD and aflQ genes. Positive strains were induced to produce aflatoxins on yeast extract sucrose and quantified using liquid chromatography-tandem mass spectrometry (LCMSMS). Aspergillus flavus was the most common contaminant, and the incidence of occurrence in Nandi and Makueni was not significantly different (82.33% and 73.26%, respectively). Toxigenic strains were more prevalent than non-toxigenic strains. All the toxigenic strains from Makueni were of the S-type while those from Nandi belonged to the l-type. Quantitative differences in aflatoxin production in vitro between isolates and between strains were detected with S strains producing relatively larger amounts of total aflatoxins, B toxins and lower values for G toxins. This was in accord with the frequent aflatoxicosis outbreaks in Makueni. However some L strains produced considerable amounts of B toxins. Given the widespread distribution of toxigenic strains in both regions, the risk of aflatoxin poisoning is high when favorable conditions for toxin production occur. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
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Open AccessArticle Comparative Cellular Toxicity of Hydrophilic and Hydrophobic Microcystins on Caco-2 Cells
Toxins 2012, 4(11), 1008-1023; doi:10.3390/toxins4111008
Received: 16 August 2012 / Revised: 8 October 2012 / Accepted: 9 October 2012 / Published: 25 October 2012
Cited by 21 | PDF Full-text (315 KB) | HTML Full-text | XML Full-text
Abstract
Microcystins (MC), cyanobacterial peptide hepatotoxins, comprise more than 100 different variants. They are rather polar molecules but some variants contain hydrophobic amino acid residues in the highly variable parts of the molecule. In MC-LF and MC-LW, the more hydrophobic phenylalanine (F) and tryptophan
[...] Read more.
Microcystins (MC), cyanobacterial peptide hepatotoxins, comprise more than 100 different variants. They are rather polar molecules but some variants contain hydrophobic amino acid residues in the highly variable parts of the molecule. In MC-LF and MC-LW, the more hydrophobic phenylalanine (F) and tryptophan (W), respectively, have replaced arginine (R) in MC-LR. Depending on the structure, microcystins are expected to have different in vivo toxicity and bioavailability, but only a few studies have considered the toxic properties of the more hydrophobic variants. The present study shows that MC-LF and MC-LW have more pronounced cytotoxic effects on Caco-2 cells as compared to those of MC-LR. Treatment of Caco-2 cells with MC-LW and especially MC-LF showed clear apoptotic features including shrinkage and blebbing, and the cell–cell adhesion was lost. An obvious reduction of cell proliferation and viability, assessed as the activity of mitochondrial dehydrogenases, was observed with MC-LF, followed by MC-LW and MC-LR. Cytotoxicity was quantified by measuring lactate dehydrogenase leakage. The more hydrophobic MC-LW and MC-LF induced markedly enhanced lactate dehydrogenase leakage compared to controls and MC-LR, indicating that the plasma membrane was damaged. All of the three toxins examined inhibited protein phosphatase 1, with MC-LF and MC-LW to a weaker extent compared to MC-LR. The higher toxic potential of the more hydrophobic microcystins could not be explained by the biophysical experiments performed. Taken together, our data show that the more hydrophobic microcystin variants induce higher toxicity in Caco-2 cells. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
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Open AccessArticle Comparative Antitumor Effect of Preventive versus Therapeutic Vaccines Employing B16 Melanoma Cells Genetically Modified to Express GM-CSF and B7.2 in a Murine Model
Toxins 2012, 4(11), 1058-1081; doi:10.3390/toxins4111058
Received: 11 July 2012 / Revised: 24 September 2012 / Accepted: 18 October 2012 / Published: 31 October 2012
Cited by 2 | PDF Full-text (1022 KB) | HTML Full-text | XML Full-text
Abstract
Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing
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Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing B16 tumor cells expressing GM-CSF and B7.2. Wild B16 cells were injected in C57BL6 mice to cause the tumor. Irradiated B16 cells transfected with GM-CSF, B7.2, or both, were processed as a preventive and therapeutic vaccination. Tumor volumes were measured and survival curves were obtained. Blood samples were taken from mice, and IgGs of each treatment group were also measured. The regulatory T cells (Treg) of selected groups were quantified using counts of images taken by confocal microscopy. Results: one hundred percent survival was achieved by preventive vaccination with the group of cells transfected with p2F_GM-CSF. Therapeutic vaccination achieved initial inhibition of tumor growth but did not secure overall survival of the animals. Classical Treg cells did not vary among the different groups in this therapeutic vaccination model. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
Open AccessArticle Apoptosis Induction by OTA and TNF-α in Cultured Primary Rat Hepatocytes and Prevention by Silibinin
Toxins 2012, 4(11), 1139-1156; doi:10.3390/toxins4111139
Received: 31 August 2012 / Revised: 24 October 2012 / Accepted: 25 October 2012 / Published: 2 November 2012
Cited by 9 | PDF Full-text (1818 KB) | HTML Full-text | XML Full-text
Abstract
In cultures of primary rat hepatocytes, apoptosis occurred after application of 20 ng/mL tumor necrosis factor alpha (TNF-α). However, this was only in the presence of 200 ng/mL of the transcriptional inhibitor actinomycin D (ActD). This toxic effect was completely prevented in the
[...] Read more.
In cultures of primary rat hepatocytes, apoptosis occurred after application of 20 ng/mL tumor necrosis factor alpha (TNF-α). However, this was only in the presence of 200 ng/mL of the transcriptional inhibitor actinomycin D (ActD). This toxic effect was completely prevented in the presence of 25 µg/mL soluble TNF-α receptor I (sTNFR I) in the supernatant of hepatocyte cell cultures. Apoptosis also occurred after application of 12.5 µmol/L ochratoxin A (OTA). However, that was not prevented by up to 500 µg/mL sTNFR I, indicating that TNF-α/TNFR I is not involved in OTA mediated apoptosis in hepatocytes. The antioxidative flavanolignan silibinin in doses from 130 to 260 µmol/L prevented chromatin condensation, caspase-3 activation, and apoptotic DNA fragmentation that were induced by OTA, by 10 mmol/L hydrogen peroxide (H2O2) and by ultraviolet (UV-C) light (50 mJ/cm2), respectively. To achieve protection by silibinin, the drug was applied to the cell cultures for 2 h in advance. OTA stimulated lipid peroxidation on cultured immortalized rat liver HPCT cells, as was revealed by malondialdehyde (MDA) production. Lipid peroxidation occurred further by H2O2 and ActD/TNF-α incubation. These reactions were also suppressed by silibinin pretreatment. We conclude that the anti-apoptotic activity of silibinin against OTA, H2O2 and ActD/ TNF-α is caused in vitro by the antioxidative effects of the flavanolignan. Furthermore, cytotoxicity of the pro-apoptotic toxins was revealed by MTT-test. When applied separately, ActD and TNF-α showed no cytotoxic effects after 24 h, but were cytotoxic if applied in combination. The used concentrations of OTA, H2O2 and the dose of UV-C caused a substantial decrease in viability within 36 h that was prevented mostly by silibinin. We conclude that silibinin is a potent protective compound against apoptosis and cytotoxicity caused by OTA and the investigated compounds. Full article
(This article belongs to the Special Issue Ochratoxins 2011-2012)
Open AccessArticle Mathematic Modeling for Optimum Conditions on Aflatoxin B1 Degradation by the Aerobic Bacterium Rhodococcus erythropolis
Toxins 2012, 4(11), 1181-1195; doi:10.3390/toxins4111181
Received: 25 July 2012 / Revised: 8 October 2012 / Accepted: 31 October 2012 / Published: 6 November 2012
Cited by 6 | PDF Full-text (304 KB) | HTML Full-text | XML Full-text
Abstract
Response surface methodology was employed to optimize the degradation conditions of AFB1 by Rhodococcus erythropolis in liquid culture. The most important factors that influence the degradation, as identified by a two-level Plackett-Burman design with six variables, were temperature, pH, liquid volume, inoculum
[...] Read more.
Response surface methodology was employed to optimize the degradation conditions of AFB1 by Rhodococcus erythropolis in liquid culture. The most important factors that influence the degradation, as identified by a two-level Plackett-Burman design with six variables, were temperature, pH, liquid volume, inoculum size, agitation speed and incubation time. Central composite design (CCD) and response surface analysis were used to further investigate the interactions between these variables and to optimize the degradation efficiency of R. erythropolis based on a second-order model. The results demonstrated that the optimal parameters were: temperature, 23.2 °C; pH, 7.17; liquid volume, 24.6 mL in 100-mL flask; inoculum size, 10%; agitation speed, 180 rpm; and incubation time, 81.9 h. Under these conditions, the degradation efficiency of R. erythropolis could reach 95.8% in liquid culture, which was increased by about three times as compared to non-optimized conditions. The result by mathematic modeling has great potential for aflatoxin removal in industrial fermentation such as in food processing and ethanol production. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
Open AccessArticle A Review of Thoracic Outlet Syndrome and the Possible Role of Botulinum Toxin in the Treatment of This Syndrome
Toxins 2012, 4(11), 1223-1235; doi:10.3390/toxins4111223
Received: 3 September 2012 / Revised: 25 October 2012 / Accepted: 31 October 2012 / Published: 7 November 2012
Cited by 5 | PDF Full-text (187 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this paper is to discuss the classification, diagnosis, pathophysiology and management of Thoracic outlet syndrome (TOS). Thoracic outlet syndrome (TOS) is a complex entity that is characterized by different neurovascular signs and symptoms involving the upper limb. TOS is defined
[...] Read more.
The objective of this paper is to discuss the classification, diagnosis, pathophysiology and management of Thoracic outlet syndrome (TOS). Thoracic outlet syndrome (TOS) is a complex entity that is characterized by different neurovascular signs and symptoms involving the upper limb. TOS is defined as upper extremity symptoms due to compression of the neurovascular bundle in the area of the neck just above the first rib. Compression is thought to occur at one or more of the three anatomical compartments: the interscalene triangle, the costoclavicular space and the retropectoralis minor spaces. The clinical presentation can include both neurogenic and vascular symptoms. TOS can be difficult to diagnose because there is no standardized objective test that can be used and the clinician must rely on history and several positive findings on physical exam. The medial antebrachial cutaneous nerve conduction may be a sensitive way to detect pathology in the lower trunks of the brachial plexus which is promising for future research. Treatment options continue to be conservative and surgical. However, for those who have failed physical therapy there is research to suggest that botulinum toxin may help with symptom relief. However, given that there has been conflicting evidence, further research is required using randomized controlled trials. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)
Open AccessArticle A Metabolomic Approach to Clarifying the Effect of AST-120 on 5/6 Nephrectomized Rats by Capillary Electrophoresis with Mass Spectrometry (CE-MS)
Toxins 2012, 4(11), 1309-1322; doi:10.3390/toxins4111309
Received: 18 July 2012 / Revised: 19 September 2012 / Accepted: 26 October 2012 / Published: 14 November 2012
Cited by 9 | PDF Full-text (708 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The oral adsorbent AST-120 is composed of spherical carbon particles and has an adsorption ability for certain small-molecular-weight compounds that accumulate in patients with chronic kidney disease (CKD). So far, very few compounds are known to be adsorbed by AST-120 in vivo.
[...] Read more.
The oral adsorbent AST-120 is composed of spherical carbon particles and has an adsorption ability for certain small-molecular-weight compounds that accumulate in patients with chronic kidney disease (CKD). So far, very few compounds are known to be adsorbed by AST-120 in vivo. To examine the effect of AST-120 in vivo, we comprehensively evaluated the plasma concentrations of 146 compounds (61 anions and 85 cations) in CKD model rats, with or without four weeks of treatment with AST-120. By capillary electrophoresis with mass spectrometry, we identified 6 anions and 17 cations that were significantly decreased by AST-120 treatment. In contrast, we also identified 2 cations that were significantly increased by AST-120. Among them, 4 anions, apart from indoxyl sulfate and hippurate, and 19 cations were newly identified in this study. The plasma levels of N-acetyl-neuraminate, 4-pyridoxate, 4-oxopentanoate, glycine, γ-guanidinobutyrate, N-γ-ethylglutamine, allantoin, cytosine, 5-methylcytosine and imidazole-4-acetate were significantly increased in the CKD model compared with the sham-operated group, and were significantly decreased by AST-120 treatment. Therefore, these 10 compounds could be added as uremic compounds that indicate the effect of AST-120 treatment. This study provides useful information not only for identifying the indicators of AST-120, but also for clarifying changes in the metabolic profile by AST-120 treatment in the clinical setting. Full article
(This article belongs to the Special Issue Uremic Toxins)
Open AccessArticle Lengthening of Insect Development on Bt Zone Results in Adult Emergence Asynchrony: Does It Influence the Effectiveness of the High Dose/Refuge Zone Strategy?
Toxins 2012, 4(11), 1323-1342; doi:10.3390/toxins4111323
Received: 26 September 2012 / Revised: 6 November 2012 / Accepted: 6 November 2012 / Published: 15 November 2012
Cited by 3 | PDF Full-text (437 KB) | HTML Full-text | XML Full-text
Abstract
The “High Dose/Refuge” strategy (HD/R) is the currently recommended Insect Resistance Management strategy (IRM) to limit resistance development to Bacillus thuringiensis (Bt) plants. This strategy requires planting a “refuge zone” composed of non-Bt plants suitable for the target insect and
[...] Read more.
The “High Dose/Refuge” strategy (HD/R) is the currently recommended Insect Resistance Management strategy (IRM) to limit resistance development to Bacillus thuringiensis (Bt) plants. This strategy requires planting a “refuge zone” composed of non-Bt plants suitable for the target insect and in close proximity to a “Bt zone” expressing a high toxin concentration. One of the main assumptions is that enough susceptible adults mate with resistant insects. However, previous studies have suggested that the high toxin concentration produced by Bt plants induces slower insect development, creating an asynchrony in emergence between the refuge and the Bt zone and leading to assortative mating between adults inside each zone. Here, we develop a deterministic model to estimate the impact of toxin concentration, emergence asynchrony and refuge zone size on the effectiveness of the HD/R strategy. We conclude that emergence asynchrony only affects resistance when toxin concentration is high and resistance is recessive. Resistance develops more rapidly and survival of susceptible insects is higher at lower toxin concentration, but in such situations, resistance is insensitive to emergence asynchrony. Full article
(This article belongs to the Special Issue Insecticidal Toxins)
Open AccessArticle Short Toxin-like Proteins Abound in Cnidaria Genomes
Toxins 2012, 4(11), 1367-1384; doi:10.3390/toxins4111367
Received: 24 September 2012 / Revised: 8 November 2012 / Accepted: 9 November 2012 / Published: 16 November 2012
Cited by 1 | PDF Full-text (842 KB) | HTML Full-text | XML Full-text
Abstract
Cnidaria is a rich phylum that includes thousands of marine species. In this study, we focused on Anthozoa and Hydrozoa that are represented by the Nematostella vectensis (Sea anemone) and Hydra magnipapillata genomes. We present a method for ranking the toxin-like candidates from
[...] Read more.
Cnidaria is a rich phylum that includes thousands of marine species. In this study, we focused on Anthozoa and Hydrozoa that are represented by the Nematostella vectensis (Sea anemone) and Hydra magnipapillata genomes. We present a method for ranking the toxin-like candidates from complete proteomes of Cnidaria. Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors from venomous animals. Fundamental features that were emphasized in training ClanTox include cysteines and their spacing along the sequences. Among the 83,000 proteins derived from Cnidaria representatives, we found 170 candidates that fulfill the properties of toxin-like-proteins, the vast majority of which were previously unrecognized as toxins. An additional 394 short proteins exhibit characteristics of toxin-like proteins at a moderate degree of confidence. Remarkably, only 11% of the predicted toxin-like proteins were previously classified as toxins. Based on our prediction methodology and manual annotation, we inferred functions for over 400 of these proteins. Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. Many of the proteins belong to small families of paralogs. We conclude that the evolutionary expansion of toxin-like proteins in Cnidaria contributes to their fitness in the complex environment of the aquatic ecosystem. Full article
(This article belongs to the Special Issue Toxins from Aquatic Organisms)
Open AccessArticle Relationship between Aflatoxin Contamination and Physiological Responses of Corn Plants under Drought and Heat Stress
Toxins 2012, 4(11), 1385-1403; doi:10.3390/toxins4111385
Received: 29 August 2012 / Revised: 13 November 2012 / Accepted: 14 November 2012 / Published: 20 November 2012
Cited by 22 | PDF Full-text (325 KB) | HTML Full-text | XML Full-text
Abstract
Increased aflatoxin contamination in corn by the fungus Aspergillus flavus is associated with frequent periods of drought and heat stress during the reproductive stages of the plants. The objective of this study was to evaluate the relationship between aflatoxin contamination and physiological responses
[...] Read more.
Increased aflatoxin contamination in corn by the fungus Aspergillus flavus is associated with frequent periods of drought and heat stress during the reproductive stages of the plants. The objective of this study was to evaluate the relationship between aflatoxin contamination and physiological responses of corn plants under drought and heat stress. The study was conducted in Stoneville, MS, USA under irrigated and non-irrigated conditions. Five commercial hybrids, P31G70, P33F87, P32B34, P31B13 and DKC63-42 and two inbred germplasm lines, PI 639055 and PI 489361, were evaluated. The plants were inoculated with Aspergillus flavus (K-54) at mid-silk stage, and aflatoxin contamination was determined on the kernels at harvest. Several physiological measurements which are indicators of stress response were determined. The results suggested that PI 639055, PI 489361 and hybrid DKC63-42 were more sensitive to drought and high temperature stress in the non-irrigated plots and P31G70 was the most tolerant among all the genotypes. Aflatoxin contamination was the highest in DKC63-42 and PI 489361 but significantly lower in P31G70. However, PI 639055, which is an aflatoxin resistant germplasm, had the lowest aflatoxin contamination, even though it was one of the most stressed genotypes. Possible reasons for these differences are discussed. These results suggested that the physiological responses were associated with the level of aflatoxin contamination in all the genotypes, except PI 639055. These and other physiological responses related to stress may help examine differences among corn genotypes in aflatoxin contamination. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)

Review

Jump to: Research

Open AccessReview Immune Dysfunction in Uremia—An Update
Toxins 2012, 4(11), 962-990; doi:10.3390/toxins4110962
Received: 6 August 2012 / Revised: 26 September 2012 / Accepted: 8 October 2012 / Published: 24 October 2012
Cited by 28 | PDF Full-text (301 KB) | HTML Full-text | XML Full-text
Abstract
Kidney dysfunction leads to disturbed renal metabolic activities and to impaired glomerular filtration, resulting in the retention of toxic solutes affecting all organs of the body. Cardiovascular disease (CVD) and infections are the main causes for the increased occurrence of morbidity and mortality
[...] Read more.
Kidney dysfunction leads to disturbed renal metabolic activities and to impaired glomerular filtration, resulting in the retention of toxic solutes affecting all organs of the body. Cardiovascular disease (CVD) and infections are the main causes for the increased occurrence of morbidity and mortality among patients with chronic kidney disease (CKD). Both complications are directly or indirectly linked to a compromised immune defense. The specific coordinated roles of polymorphonuclear leukocytes (PMNLs), monocytes/macrophages, lymphocytes and antigen-presenting cells (APCs) in maintaining an efficient immune response are affected. Their normal response can be impaired, giving rise to infectious diseases or pre-activated/primed, leading to inflammation and consequently to CVD. Whereas the coordinated removal via apoptosis of activated immune cells is crucial for the resolution of inflammation, inappropriately high apoptotic rates lead to a diminished immune response. In uremia, the balance between pro- and anti-inflammatory and between pro- and anti-apoptotic factors is disturbed. This review summarizes the interrelated parameters interfering with the immune response in uremia, with a special focus on the non-specific immune response and the role of uremic toxins. Full article
(This article belongs to the Special Issue Uremic Toxins)
Open AccessReview Current Understanding on Aflatoxin Biosynthesis and Future Perspective in Reducing Aflatoxin Contamination
Toxins 2012, 4(11), 1024-1057; doi:10.3390/toxins4111024
Received: 17 August 2012 / Revised: 8 October 2012 / Accepted: 9 October 2012 / Published: 25 October 2012
Cited by 39 | PDF Full-text (382 KB) | HTML Full-text | XML Full-text
Abstract
Traditional molecular techniques have been used in research in discovering the genes and enzymes that are involved in aflatoxin formation and genetic regulation. We cloned most, if not all, of the aflatoxin pathway genes. A consensus gene cluster for aflatoxin biosynthesis was discovered
[...] Read more.
Traditional molecular techniques have been used in research in discovering the genes and enzymes that are involved in aflatoxin formation and genetic regulation. We cloned most, if not all, of the aflatoxin pathway genes. A consensus gene cluster for aflatoxin biosynthesis was discovered in 2005. The factors that affect aflatoxin formation have been studied. In this report, the author summarized the current status of research progress and future possibilities that may be used for solving aflatoxin contamination. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
Open AccessReview Scorpion Toxins Specific for Potassium (K+) Channels: A Historical Overview of Peptide Bioengineering
Toxins 2012, 4(11), 1082-1119; doi:10.3390/toxins4111082
Received: 14 September 2012 / Revised: 22 October 2012 / Accepted: 23 October 2012 / Published: 1 November 2012
Cited by 26 | PDF Full-text (673 KB) | HTML Full-text | XML Full-text
Abstract
Scorpion toxins have been central to the investigation and understanding of the physiological role of potassium (K+) channels and their expansive function in membrane biophysics. As highly specific probes, toxins have revealed a great deal about channel structure and the correlation
[...] Read more.
Scorpion toxins have been central to the investigation and understanding of the physiological role of potassium (K+) channels and their expansive function in membrane biophysics. As highly specific probes, toxins have revealed a great deal about channel structure and the correlation between mutations, altered regulation and a number of human pathologies. Radio- and fluorescently-labeled toxin isoforms have contributed to localization studies of channel subtypes in expressing cells, and have been further used in competitive displacement assays for the identification of additional novel ligands for use in research and medicine. Chimeric toxins have been designed from multiple peptide scaffolds to probe channel isoform specificity, while advanced epitope chimerization has aided in the development of novel molecular therapeutics. Peptide backbone cyclization has been utilized to enhance therapeutic efficiency by augmenting serum stability and toxin half-life in vivo as a number of K+-channel isoforms have been identified with essential roles in disease states ranging from HIV, T-cell mediated autoimmune disease and hypertension to various cardiac arrhythmias and Malaria. Bioengineered scorpion toxins have been monumental to the evolution of channel science, and are now serving as templates for the development of invaluable experimental molecular therapeutics. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview Advances in Deoxynivalenol Toxicity Mechanisms: The Brain as a Target
Toxins 2012, 4(11), 1120-1138; doi:10.3390/toxins4111120
Received: 18 September 2012 / Revised: 18 October 2012 / Accepted: 19 October 2012 / Published: 1 November 2012
Cited by 18 | PDF Full-text (1826 KB) | HTML Full-text | XML Full-text
Abstract
Deoxynivalenol (DON), mainly produced by Fusarium fungi, and also commonly called vomitoxin, is a trichothecene mycotoxin. It is one of the most abundant trichothecenes which contaminate cereals consumed by farm animals and humans. The extent of cereal contamination is strongly associated with rainfall
[...] Read more.
Deoxynivalenol (DON), mainly produced by Fusarium fungi, and also commonly called vomitoxin, is a trichothecene mycotoxin. It is one of the most abundant trichothecenes which contaminate cereals consumed by farm animals and humans. The extent of cereal contamination is strongly associated with rainfall and moisture at the time of flowering and with grain storage conditions. DON consumption may result in intoxication, the severity of which is dose-dependent and may lead to different symptoms including anorexia, vomiting, reduced weight gain, neuroendocrine changes, immunological effects, diarrhea, leukocytosis, hemorrhage or circulatory shock. During the last two decades, many studies have described DON toxicity using diverse animal species as a model. While the action of the toxin on peripheral organs and tissues is well documented, data illustrating its effect on the brain are significantly less abundant. Yet, DON is known to affect the central nervous system. Recent studies have provided new evidence and detail regarding the action of the toxin on the brain. The purpose of the present review is to summarize critical studies illustrating this central action of the toxin and to suggest research perspectives in this field. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview Factors Influencing Deoxynivalenol Accumulation in Small Grain Cereals
Toxins 2012, 4(11), 1157-1180; doi:10.3390/toxins4111157
Received: 28 September 2012 / Revised: 24 October 2012 / Accepted: 2 November 2012 / Published: 6 November 2012
Cited by 32 | PDF Full-text (1393 KB) | HTML Full-text | XML Full-text
Abstract
Deoxynivalenol (DON) is a mycotoxin produced by the plant pathogenic fungi Fusarium graminearum and F. culmorum. These and other closely related fungi cause a disease known as Fusarium head blight (FHB) in small grain cereals. Other mycotoxins produced by FHB-causing fungi include nivalenol,
[...] Read more.
Deoxynivalenol (DON) is a mycotoxin produced by the plant pathogenic fungi Fusarium graminearum and F. culmorum. These and other closely related fungi cause a disease known as Fusarium head blight (FHB) in small grain cereals. Other mycotoxins produced by FHB-causing fungi include nivalenol, T-2 toxin, and zearalenone. Ingestion of mycotoxin-contaminated food and feed can lead to toxicosis in humans and animals, respectively. DON is the predominant and most economically important of these mycotoxins in the majority of small grain-producing regions of the world. This review examines the factors that influence DON accumulation in small grain cereals from an agricultural perspective. The occurrence and economic importance of FHB and DON in small grain cereals, epidemiological factors and cereal production practices that favor FHB development and DON accumulation in grain under field conditions, and regulatory/advisory standards for DON in food and feed are discussed. This information can be used to develop strategies that reduce DON accumulation in grain before harvest and to mitigate the human and animal health risks associated with DON contamination of food and feed. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
Open AccessReview Emerging Opportunities for Serotypes of Botulinum Neurotoxins
Toxins 2012, 4(11), 1196-1222; doi:10.3390/toxins4111196
Received: 6 July 2012 / Revised: 2 October 2012 / Accepted: 29 October 2012 / Published: 7 November 2012
Cited by 6 | PDF Full-text (1054 KB) | HTML Full-text | XML Full-text
Abstract
Background: Two decades ago, botulinum neurotoxin (BoNT) type A was introduced to the commercial market. Subsequently, the toxin was approved by the FDA to address several neurological syndromes, involving muscle, nerve, and gland hyperactivity. These syndromes have typically been associated with abnormalities in
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Background: Two decades ago, botulinum neurotoxin (BoNT) type A was introduced to the commercial market. Subsequently, the toxin was approved by the FDA to address several neurological syndromes, involving muscle, nerve, and gland hyperactivity. These syndromes have typically been associated with abnormalities in cholinergic transmission. Despite the multiplicity of botulinal serotypes (designated as types A through G), therapeutic preparations are currently only available for BoNT types A and B. However, other BoNT serotypes are under study for possible clinical use and new clinical indications; Objective: To review the current research on botulinum neurotoxin serotypes A-G, and to analyze potential applications within basic science and clinical settings; Conclusions: The increasing understanding of botulinal neurotoxin pathophysiology, including the neurotoxin’s effects on specific neuronal populations, will help us in tailoring treatments for specific diagnoses, symptoms and patients. Scientists and clinicians should be aware of the full range of available data involving neurotoxin subtypes A-G. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)
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Open AccessReview Conotoxins Targeting Neuronal Voltage-Gated Sodium Channel Subtypes: Potential Analgesics?
Toxins 2012, 4(11), 1236-1260; doi:10.3390/toxins4111236
Received: 10 October 2012 / Revised: 5 November 2012 / Accepted: 5 November 2012 / Published: 8 November 2012
Cited by 29 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text
Abstract
Voltage-gated sodium channels (VGSC) are the primary mediators of electrical signal amplification and propagation in excitable cells. VGSC subtypes are diverse, with different biophysical and pharmacological properties, and varied tissue distribution. Altered VGSC expression and/or increased VGSC activity in sensory neurons is characteristic
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Voltage-gated sodium channels (VGSC) are the primary mediators of electrical signal amplification and propagation in excitable cells. VGSC subtypes are diverse, with different biophysical and pharmacological properties, and varied tissue distribution. Altered VGSC expression and/or increased VGSC activity in sensory neurons is characteristic of inflammatory and neuropathic pain states. Therefore, VGSC modulators could be used in prospective analgesic compounds. VGSCs have specific binding sites for four conotoxin families: μ-, μO-, δ- and ί-conotoxins. Various studies have identified that the binding site of these peptide toxins is restricted to well-defined areas or domains. To date, only the μ- and μO-family exhibit analgesic properties in animal pain models. This review will focus on conotoxins from the μ- and μO-families that act on neuronal VGSCs. Examples of how these conotoxins target various pharmacologically important neuronal ion channels, as well as potential problems with the development of drugs from conotoxins, will be discussed. Full article
(This article belongs to the Special Issue Animal Toxins Targeting Ion Channels Involved in Pain)
Open AccessReview Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals
Toxins 2012, 4(11), 1261-1287; doi:10.3390/toxins4111261
Received: 17 September 2012 / Revised: 1 November 2012 / Accepted: 2 November 2012 / Published: 8 November 2012
Cited by 36 | PDF Full-text (445 KB) | HTML Full-text | XML Full-text
Abstract
Food-borne diseases are estimated at 76 million illnesses and 5000 deaths every year in the United States with the greatest burden on young children, the elderly and immunocompromised populations. The impact of efficient food distribution systems and a truly global food supply ensures
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Food-borne diseases are estimated at 76 million illnesses and 5000 deaths every year in the United States with the greatest burden on young children, the elderly and immunocompromised populations. The impact of efficient food distribution systems and a truly global food supply ensures that outbreaks, previously sporadic and contained locally, are far more widespread and emerging pathogens have far more frequent infection opportunities. Enterohemorrhagic E. coli is an emerging food- and water-borne pathogen family whose Shiga-like toxins induce painful hemorrhagic colitis with potentially lethal complications of hemolytic uremic syndrome (HUS). The clinical manifestations of Shiga toxin-induced HUS overlap with other related syndromes yet molecular mechanisms differ considerably. As discussed herein, understanding these differences and the novel properties of the toxins is imperative for clinical management decisions, design of appropriate animal models, and choices of adjunctive therapeutics. The emergence of new strains with rapidly aggressive virulence makes clinical and research initiatives in this field a high public health priority. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview Pharmacophore Selection and Redesign of Non-nucleotide Inhibitors of Anthrax Edema Factor
Toxins 2012, 4(11), 1288-1300; doi:10.3390/toxins4111288
Received: 24 September 2012 / Revised: 25 October 2012 / Accepted: 1 November 2012 / Published: 8 November 2012
Cited by 9 | PDF Full-text (667 KB) | HTML Full-text | XML Full-text
Abstract
Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF), an adenylyl cyclase,
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Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin’s basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC) in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera. Full article
(This article belongs to the Special Issue Anthrax Toxin)
Open AccessReview Glucan–Resveratrol–Vitamin C Combination Offers Protection against Toxic Agents
Toxins 2012, 4(11), 1301-1308; doi:10.3390/toxins4111301
Received: 17 August 2012 / Revised: 26 September 2012 / Accepted: 19 October 2012 / Published: 9 November 2012
Cited by 6 | PDF Full-text (546 KB) | HTML Full-text | XML Full-text
Abstract
Biological immunomodulators are routinely evaluated as a natural source of molecules with profound effects on the immune system. They belong to a group of physiologically active compounds, collectively termed biological response modifiers. Most of the studies were focused on immune system stimulation. Recently,
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Biological immunomodulators are routinely evaluated as a natural source of molecules with profound effects on the immune system. They belong to a group of physiologically active compounds, collectively termed biological response modifiers. Most of the studies were focused on immune system stimulation. Recently, they have become the focus of studies seeking molecules that are able to overcome negative effects of various immunotoxins. This paper concentrates on the effects of a glucan/resveratrol/vitamin C combination on immunosuppressive effects of mercury and perfluorinated hydrocarbons. Effects described in this review have strong clinical potential, as environmental contaminants have adverse effects on all aspects of the immune system and represent a serious threat to the health of both humans and animals. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
Open AccessReview PI3K/Akt/mTOR, a Pathway Less Recognized for Staphylococcal Superantigen-Induced Toxicity
Toxins 2012, 4(11), 1343-1366; doi:10.3390/toxins4111343
Received: 27 September 2012 / Revised: 12 November 2012 / Accepted: 13 November 2012 / Published: 15 November 2012
Cited by 5 | PDF Full-text (949 KB) | HTML Full-text | XML Full-text
Abstract
Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic toxins cause diseases in humans and laboratory animals by activating cells of the immune system. These toxins bind directly to the major histocompatibility complex (MHC) class II molecules on antigen-presenting cells and specific Vβ regions
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Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic toxins cause diseases in humans and laboratory animals by activating cells of the immune system. These toxins bind directly to the major histocompatibility complex (MHC) class II molecules on antigen-presenting cells and specific Vβ regions of T-cell receptors (TCR), resulting in hyperactivation of both T lymphocytes and monocytes/macrophages. Activated host cells produce excessive amounts of proinflammatory cytokines and chemokines, especially tumor necrosis factor α, interleukin 1 (IL-1), IL-2, interferon γ (IFNγ), and macrophage chemoattractant protein 1 causing clinical symptoms of fever, hypotension, and shock. The well-explored signal transduction pathways for SEB-induced toxicity downstream from TCR/MHC ligation and interaction of cell surface co-stimulatory molecules include the mitogen-activated protein kinase cascades and cytokine receptor signaling, culminating in NFκB activation. Independently, IL-2, IFNγ, and chemokines from activated T cells signal via the phosphoinositide 3-kinase (PI3K), the serine/threonine kinases, Akt and mammalian target of rapamycin (mTOR) pathways. This article reviews the signaling molecules induced by superantigens in the activation of PI3K/Akt/mTOR pathways leading to staphylococcal superantigen-induced toxicity and updates potential therapeutics against superantigens. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview Botulinum Toxin Physiology in Focal Hand and Cranial Dystonia
Toxins 2012, 4(11), 1404-1414; doi:10.3390/toxins4111404
Received: 3 September 2012 / Revised: 24 October 2012 / Accepted: 9 November 2012 / Published: 20 November 2012
Cited by 8 | PDF Full-text (148 KB) | HTML Full-text | XML Full-text
Abstract
The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features,
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The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features, such as task specificity in focal hand dystonia which is not a common feature of cranial dystonia. The physiologic effects of botulinum toxin in these 2 disorders also show both similarities and differences. This paper compares and contrasts the physiology of focal hand and cranial dystonias and of botulinum toxin in the management of these disorders. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)

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