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Toxins, Volume 5, Issue 4 (April 2013), Pages 605-864

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Research

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Open AccessArticle Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome
Toxins 2013, 5(4), 605-617; doi:10.3390/toxins5040605
Received: 18 March 2013 / Revised: 1 April 2013 / Accepted: 3 April 2013 / Published: 11 April 2013
Cited by 18 | PDF Full-text (63 KB) | HTML Full-text | XML Full-text
Abstract
Over the past 20 years, exposure to mycotoxin producing mold has been recognized as a significant health risk. Scientific literature has demonstrated mycotoxins as possible causes of human disease in water-damaged buildings (WDB). This study was conducted to determine if selected mycotoxins could
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Over the past 20 years, exposure to mycotoxin producing mold has been recognized as a significant health risk. Scientific literature has demonstrated mycotoxins as possible causes of human disease in water-damaged buildings (WDB). This study was conducted to determine if selected mycotoxins could be identified in human urine from patients suffering from chronic fatigue syndrome (CFS). Patients (n = 112) with a prior diagnosis of CFS were evaluated for mold exposure and the presence of mycotoxins in their urine. Urine was tested for aflatoxins (AT), ochratoxin A (OTA) and macrocyclic trichothecenes (MT) using Enzyme Linked Immunosorbent Assays (ELISA). Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin (one in the equivocal range). Almost 30% of the cases had more than one mycotoxin present. OTA was the most prevalent mycotoxin detected (83%) with MT as the next most common (44%). Exposure histories indicated current and/or past exposure to WDB in over 90% of cases. Environmental testing was performed in the WDB from a subset of these patients. This testing revealed the presence of potentially mycotoxin producing mold species and mycotoxins in the environment of the WDB. Prior testing in a healthy control population with no history of exposure to a WDB or moldy environment (n = 55) by the same laboratory, utilizing the same methods, revealed no positive cases at the limits of detection. Full article
(This article belongs to the Special Issue Mycotoxins and Human Diseases)
Open AccessArticle Multiple Membrane Interactions and Versatile Vesicle Deformations Elicited by Melittin
Toxins 2013, 5(4), 637-664; doi:10.3390/toxins5040637
Received: 18 February 2013 / Revised: 2 April 2013 / Accepted: 10 April 2013 / Published: 17 April 2013
Cited by 12 | PDF Full-text (6923 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Melittin induces various reactions in membranes and has been widely studied as a model for membrane-interacting peptide; however, the mechanism whereby melittin elicits its effects remains unclear. Here, we observed melittin-induced changes in individual giant liposomes using direct real-time imaging by dark-field optical
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Melittin induces various reactions in membranes and has been widely studied as a model for membrane-interacting peptide; however, the mechanism whereby melittin elicits its effects remains unclear. Here, we observed melittin-induced changes in individual giant liposomes using direct real-time imaging by dark-field optical microscopy, and the mechanisms involved were correlated with results obtained using circular dichroism, cosedimentation, fluorescence quenching of tryptophan residues, and electron microscopy. Depending on the concentration of negatively charged phospholipids in the membrane and the molecular ratio between lipid and melittin, melittin induced the “increasing membrane area”, “phased shrinkage”, or “solubilization” of liposomes. In phased shrinkage, liposomes formed small particles on their surface and rapidly decreased in size. Under conditions in which the increasing membrane area, phased shrinkage, or solubilization were mainly observed, the secondary structure of melittin was primarily estimated as an α-helix, β-like, or disordered structure, respectively. When the increasing membrane area or phased shrinkage occurred, almost all melittin was bound to the membranes and reached more hydrophobic regions of the membranes than when solubilization occurred. These results indicate that the various effects of melittin result from its ability to adopt various structures and membrane-binding states depending on the conditions. Full article
(This article belongs to the Special Issue Pore-Forming Toxins)
Open AccessArticle Carmustine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane
Toxins 2013, 5(4), 703-716; doi:10.3390/toxins5040703
Received: 20 February 2013 / Revised: 7 April 2013 / Accepted: 10 April 2013 / Published: 19 April 2013
Cited by 45 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text
Abstract
The nitrosourea alkylating agent, carmustine, is used as chemotherapeutic drug in several malignancies. The substance triggers tumor cell apoptosis. Side effects of carmustine include myelotoxicity with anemia. At least in theory, anemia could partly be due to stimulation of eryptosis, the suicidal
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The nitrosourea alkylating agent, carmustine, is used as chemotherapeutic drug in several malignancies. The substance triggers tumor cell apoptosis. Side effects of carmustine include myelotoxicity with anemia. At least in theory, anemia could partly be due to stimulation of eryptosis, the suicidal death of erythrocytes, characterized by cell shrinkage and breakdown of phosphatidylserine asymmetry of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i). The present study tested whether carmustine triggers eryptosis. To this end [Ca2+]i was estimated from Fluo3 fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin V binding, and hemolysis from hemoglobin release. As a result a 48 h exposure to carmustine (≥25 µM) significantly increased [Ca2+]i, decreased forward scatter and increased annexin V binding. The effect on annexin V binding was significantly blunted in the absence of extracellular Ca2+. In conclusion, carmustine stimulates eryptosis at least partially by increasing cytosolic Ca2+ activity. Full article
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Open AccessArticle Phylogenetic Study of Polyketide Synthases and Nonribosomal Peptide Synthetases Involved in the Biosynthesis of Mycotoxins
Toxins 2013, 5(4), 717-742; doi:10.3390/toxins5040717
Received: 27 February 2013 / Revised: 22 March 2013 / Accepted: 10 April 2013 / Published: 19 April 2013
Cited by 15 | PDF Full-text (1005 KB) | HTML Full-text | XML Full-text
Abstract
Polyketide synthase (PKSs) and nonribosomal peptide synthetase (NRPSs) are large multimodular enzymes involved in biosynthesis of polyketide and peptide toxins produced by fungi. Furthermore, hybrid enzymes, in which a reducing PKS region is fused to a single NRPS module, are also responsible of
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Polyketide synthase (PKSs) and nonribosomal peptide synthetase (NRPSs) are large multimodular enzymes involved in biosynthesis of polyketide and peptide toxins produced by fungi. Furthermore, hybrid enzymes, in which a reducing PKS region is fused to a single NRPS module, are also responsible of the synthesis of peptide-polyketide metabolites in fungi. The genes encoding for PKSs and NRPSs have been exposed to complex evolutionary mechanisms, which have determined the great number and diversity of metabolites. In this study, we considered the most important polyketide and peptide mycotoxins and, for the first time, a phylogenetic analysis of both PKSs and NRPSs involved in their biosynthesis was assessed using two domains for each enzyme: β-ketosynthase (KS) and acyl-transferase (AT) for PKSs; adenylation (A) and condensation (C) for NRPSs. The analysis of both KS and AT domains confirmed the differentiation of the three classes of highly, partially and non-reducing PKSs. Hybrid PKS-NRPSs involved in mycotoxins biosynthesis grouped together in the phylogenetic trees of all the domains analyzed. For most mycotoxins, the corresponding biosynthetic enzymes from distinct fungal species grouped together, except for PKS and NRPS involved in ochratoxin A biosynthesis, for which an unlike process of evolution could be hypothesized in different species. Full article
Open AccessArticle Continuation of Long-Term Care for Cervical Dystonia at an Academic Movement Disorders Clinic
Toxins 2013, 5(4), 776-783; doi:10.3390/toxins5040776
Received: 19 March 2013 / Revised: 12 April 2013 / Accepted: 15 April 2013 / Published: 23 April 2013
Cited by 4 | PDF Full-text (194 KB) | HTML Full-text | XML Full-text
Abstract
Patients with cervical dystonia (CD) receive much of their care at university based hospital outpatient clinics. This study aimed to describe the clinical characteristics and treatment experiences of patients who continued care at our university based movement disorders clinic, and to document the
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Patients with cervical dystonia (CD) receive much of their care at university based hospital outpatient clinics. This study aimed to describe the clinical characteristics and treatment experiences of patients who continued care at our university based movement disorders clinic, and to document the reasons for which a subset discontinued care. Seventy patients (77% female) were recruited from all patients at the clinic (n = 323). Most (93%) were treated with botulinum neurotoxin (BoNT) injection, and onabotulinumtoxinA was initially used in 97%. The average dose of onabotulinumtoxinA was 270.4 U (range 50–500) and the median number of injections was 14 (range: 1–39). Twenty one patients later received at least one cycle of rimabotulinumtoxinB (33%); of those, 10 switched back to onabotulinumtoxinA (48%). The initial rimabotulinumtoxinB dose averaged 11,996 units (range: 3000–25,000 over 1–18 injections). Twenty one patients (30%) discontinued care. Reasons cited included suboptimal response to BoNT therapy (62%), excessive cost (24%), excessive travel burden (10%), and side effects of BoNT therapy (10%). Most patients (76%) did not seek further care after leaving the clinic. Patients who terminated care received fewer treatment cycles (5.5 vs. 13.0, p = 0.020). There were no other identifiable differences between groups in gender, age, disease characteristics, toxin dose, or toxin formulation. These results indicate that a significant number of CD patients discontinue care due to addressable barriers to access, including cost and travel burden, and that when leaving specialty care, patients often discontinue treatment altogether. These data highlight the need for new initiatives to reduce out-of-pocket costs, as well as training for community physicians on neurotoxin injection in order to lessen the travel burden patients must accept in order to receive standard-of-care treatments. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)
Open AccessArticle Effect of Low Dose of Fumonisins on Pig Health: Immune Status, Intestinal Microbiota and Sensitivity to Salmonella
Toxins 2013, 5(4), 841-864; doi:10.3390/toxins5040841
Received: 7 February 2013 / Revised: 12 April 2013 / Accepted: 12 April 2013 / Published: 23 April 2013
Cited by 7 | PDF Full-text (302 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to measure the effects of chronic exposure to fumonisins via the ingestion of feed containing naturally contaminated corn in growing pigs infected or not with Salmonella spp. This exposure to a moderate dietary concentration of fumonisins (11.8
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The objective of this study was to measure the effects of chronic exposure to fumonisins via the ingestion of feed containing naturally contaminated corn in growing pigs infected or not with Salmonella spp. This exposure to a moderate dietary concentration of fumonisins (11.8 ppm) was sufficient to induce a biological effect in pigs (Sa/So ratio), but no mortality or pathology was observed over 63 days of exposure. No mortality or related clinical signs, even in cases of inoculation with Salmonella (5 × 104 CFU), were observed either. Fumonisins, at these concentrations, did not affect the ability of lymphocytes to proliferate in the presence of mitogens, but after seven days post-inoculation they led to inhibition of the ability of specific Salmonella lymphocytes to proliferate following exposure to a specific Salmonella antigen. However, the ingestion of fumonisins had no impact on Salmonella translocation or seroconversion in inoculated pigs. The inoculation of Salmonella did not affect faecal microbiota profiles, but exposure to moderate concentrations of fumonisins transiently affected the digestive microbiota balance. In cases of co-infection with fumonisins and Salmonella, the microbiota profiles were rapidly and clearly modified as early as 48 h post-Salmonella inoculation. Therefore under these experimental conditions, exposure to an average concentration of fumonisins in naturally contaminated feed had no effect on pig health but did affect the digestive microbiota balance, with Salmonella exposure amplifying this phenomenon. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)

Review

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Open AccessReview More Than a Pore: The Cellular Response to Cholesterol-Dependent Cytolysins
Toxins 2013, 5(4), 618-636; doi:10.3390/toxins5040618
Received: 1 March 2013 / Revised: 7 April 2013 / Accepted: 7 April 2013 / Published: 12 April 2013
Cited by 23 | PDF Full-text (333 KB) | HTML Full-text | XML Full-text
Abstract
Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately
[...] Read more.
Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell. Full article
(This article belongs to the Special Issue Pore-Forming Toxins)
Open AccessReview The Snake Venom Rhodocytin from Calloselasma rhodostoma— A Clinically Important Toxin and a Useful Experimental Tool for Studies of C-Type Lectin-like Receptor 2 (CLEC-2)
Toxins 2013, 5(4), 665-674; doi:10.3390/toxins5040665
Received: 11 March 2013 / Revised: 1 April 2013 / Accepted: 7 April 2013 / Published: 17 April 2013
PDF Full-text (192 KB) | HTML Full-text | XML Full-text
Abstract
The snake venom, rhodocytin, from the Malayan viper, Calloselasma rhodostoma, and the endogenous podoplanin are identified as ligands for the C-type lectin-like receptor 2 (CLEC-2). The snakebites caused by Calloselasma rhodostoma cause a local reaction with swelling, bleeding and eventually necrosis, together
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The snake venom, rhodocytin, from the Malayan viper, Calloselasma rhodostoma, and the endogenous podoplanin are identified as ligands for the C-type lectin-like receptor 2 (CLEC-2). The snakebites caused by Calloselasma rhodostoma cause a local reaction with swelling, bleeding and eventually necrosis, together with a systemic effect on blood coagulation with distant bleedings that can occur in many different organs. This clinical picture suggests that toxins in the venom have effects on endothelial cells and vessel permeability, extravasation and, possibly, activation of immunocompetent cells, as well as effects on platelets and the coagulation cascade. Based on the available biological studies, it seems likely that ligation of CLEC-2 contributes to local extravasation, inflammation and, possibly, local necrosis, due to microthrombi and ischemia, whereas other toxins may be more important for the distant hemorrhagic complications. However, the venom contains several toxins and both local, as well as distant, symptoms are probably complex reactions that cannot be explained by the effects of rhodocytin and CLEC-2 alone. The in vivo reactions to rhodocytin are thus examples of toxin-induced crosstalk between coagulation (platelets), endothelium and inflammation (immunocompetent cells). Very few studies have addressed this crosstalk as a part of the pathogenesis behind local and systemic reactions to Calloselasma rhodostoma bites. The author suggests that detailed biological studies based on an up-to-date methodology of local and systemic reactions to Calloselasma rhodostoma bites should be used as a hypothesis-generating basis for future functional studies of the CLEC-2 receptor. It will not be possible to study the effects of purified toxins in humans, but the development of animal models (e.g., cutaneous injections of rhodocytin to mimic snakebites) would supplement studies in humans. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
Open AccessReview Towards Systems Biology of Mycotoxin Regulation
Toxins 2013, 5(4), 675-682; doi:10.3390/toxins5040675
Received: 25 February 2013 / Revised: 22 March 2013 / Accepted: 10 April 2013 / Published: 18 April 2013
Cited by 3 | PDF Full-text (823 KB) | HTML Full-text | XML Full-text
Abstract
Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of
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Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of systems biology, but the last decade of research is leading us closer than ever to this approach. Past research has delineated multiple levels of regulation in the pathways leading to the biosynthesis of secondary metabolites, including mycotoxins. At the top of this hierarchy, the global or master transcriptional regulators perceive various environmental cues such as climatic conditions, the availability of nutrients, and the developmental stages of the organism. Information accumulated from various inputs is integrated through a complex web of signalling networks to generate the eventual outcome. This review will focus on adapting techniques such as chemical and other genetic tools available in the model system Saccharomyces cerevisiae, to disentangle the various biological networks involved in the biosynthesis of mycotoxins in the Fusarium spp. Full article
Open AccessReview Oxidative Stress-Related Transcription Factors in the Regulation of Secondary Metabolism
Toxins 2013, 5(4), 683-702; doi:10.3390/toxins5040683
Received: 5 March 2013 / Revised: 1 April 2013 / Accepted: 9 April 2013 / Published: 18 April 2013
Cited by 36 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
There is extensive and unequivocal evidence that secondary metabolism in filamentous fungi and plants is associated with oxidative stress. In support of this idea, transcription factors related to oxidative stress response in yeast, plants, and fungi have been shown to participate in controlling
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There is extensive and unequivocal evidence that secondary metabolism in filamentous fungi and plants is associated with oxidative stress. In support of this idea, transcription factors related to oxidative stress response in yeast, plants, and fungi have been shown to participate in controlling secondary metabolism. Aflatoxin biosynthesis, one model of secondary metabolism, has been demonstrated to be triggered and intensified by reactive oxygen species buildup. An oxidative stress-related bZIP transcription factor AtfB is a key player in coordinate expression of antioxidant genes and genes involved in aflatoxin biosynthesis. Recent findings from our laboratory provide strong support for a regulatory network comprised of at least four transcription factors that bind in a highly coordinated and timely manner to promoters of the target genes and regulate their expression. In this review, we will focus on transcription factors involved in co-regulation of aflatoxin biosynthesis with oxidative stress response in aspergilli, and we will discuss the relationship of known oxidative stress-associated transcription factors and secondary metabolism in other organisms. We will also talk about transcription factors that are involved in oxidative stress response, but have not yet been demonstrated to be affiliated with secondary metabolism. The data support the notion that secondary metabolism provides a secondary line of defense in cellular response to oxidative stress. Full article
Open AccessReview Review of the Inhibition of Biological Activities of Food-Related Selected Toxins by Natural Compounds
Toxins 2013, 5(4), 743-775; doi:10.3390/toxins5040743
Received: 27 March 2013 / Revised: 5 April 2013 / Accepted: 16 April 2013 / Published: 23 April 2013
Cited by 26 | PDF Full-text (961 KB) | HTML Full-text | XML Full-text
Abstract
There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term ‘chemical genetics’ has been used to describe this approach. This overview attempts to survey and consolidate the
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There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term ‘chemical genetics’ has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol
Toxins 2013, 5(4), 784-820; doi:10.3390/toxins5040784
Received: 25 February 2013 / Revised: 11 April 2013 / Accepted: 12 April 2013 / Published: 23 April 2013
Cited by 83 | PDF Full-text (2006 KB) | HTML Full-text | XML Full-text
Abstract
Mycotoxins are fungal secondary metabolites contaminating food and causing toxicity to animals and humans. Among the various mycotoxins found in crops used for food and feed production, the trichothecene toxin deoxynivalenol (DON or vomitoxin) is one of the most prevalent and hazardous. In
[...] Read more.
Mycotoxins are fungal secondary metabolites contaminating food and causing toxicity to animals and humans. Among the various mycotoxins found in crops used for food and feed production, the trichothecene toxin deoxynivalenol (DON or vomitoxin) is one of the most prevalent and hazardous. In addition to native toxins, food also contains a large amount of plant and fungal derivatives of DON, including acetyl-DON (3 and 15ADON), glucoside-DON (D3G), and potentially animal derivatives such as glucuronide metabolites (D3 and D15GA) present in animal tissues (e.g., blood, muscle and liver tissue). The present review summarizes previous and very recent experimental data collected in vivo and in vitro regarding the transport, detoxification/metabolism and physiological impact of DON and its derivatives on intestinal, immune, endocrine and neurologic functions during their journey from the gut to the brain. Full article
(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)
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Open AccessReview Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins
Toxins 2013, 5(4), 821-840; doi:10.3390/toxins5040821
Received: 12 February 2013 / Revised: 27 March 2013 / Accepted: 12 April 2013 / Published: 23 April 2013
Cited by 32 | PDF Full-text (497 KB) | HTML Full-text | XML Full-text
Abstract
Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B
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Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent. Full article
(This article belongs to the Special Issue Neurotoxins: Health Threats and Biological Tools)

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