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Toxins, Volume 5, Issue 1 (January 2013), Pages 1-202

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Research

Jump to: Review, Other

Open AccessArticle Differences in Susceptibility to Okadaic Acid, a Diarrhetic Shellfish Poisoning Toxin, between Male and Female Mice
Toxins 2013, 5(1), 9-15; doi:10.3390/toxins5010009
Received: 8 November 2012 / Revised: 14 December 2012 / Accepted: 21 December 2012 / Published: 27 December 2012
Cited by 4 | PDF Full-text (171 KB) | HTML Full-text | XML Full-text
Abstract
The mouse bioassay (MBA) for diarrhetic shellfish poisoning (DSP) toxins has been widely used in many countries of the world. In the Japanese and EU methods, male mice are designated to be used for MBA. Female mice were described to be less susceptible
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The mouse bioassay (MBA) for diarrhetic shellfish poisoning (DSP) toxins has been widely used in many countries of the world. In the Japanese and EU methods, male mice are designated to be used for MBA. Female mice were described to be less susceptible than male mice. To the best of our knowledge, however, there have been no reports on the details of sex differences in susceptibility to DSP toxins. In this study, we investigated whether, and to what extent, female mice are less sensitive to DSP toxins. A lethal dose of okadaic acid (OA), one of the representative DSP toxins, was injected intraperitoneally into mice. The mice were observed until 24 hours after injection. Both male and female mice of ICR and ddY strains, which are designated in the Japanese official method, were compared. All the mice were four weeks old and weighed 18–20 g. The experiments were repeated twice. The lethality was 70%–100%. Survival analysis showed no sex differences in susceptibility to OA, but ICR female mice showed significant resistance compared with other groups in one out of two trials. These results indicate that sex differences were not clear but, nonetheless, male mice showed more stable results. Full article
(This article belongs to the Special Issue Toxins from Aquatic Organisms)
Open AccessArticle Onabotulinumtoxin A for Treating Overactive/Poor Compliant Bladders in Children and Adolescents with Neurogenic Bladder Secondary to Myelomeningocele
Toxins 2013, 5(1), 16-24; doi:10.3390/toxins5010016
Received: 19 November 2012 / Revised: 19 December 2012 / Accepted: 21 December 2012 / Published: 28 December 2012
Cited by 8 | PDF Full-text (578 KB) | HTML Full-text | XML Full-text
Abstract
This retrospective study was performed to verify the efficacy and safety of Onabotulinumtoxin A (BTX-A) in treating children with neurogenic bladder (NB) secondary to myelomeningocele (MMC) with detrusor overactivity/low compliance. From January 2002 to June 2011, 47 patients out of 68 with neuropathic
[...] Read more.
This retrospective study was performed to verify the efficacy and safety of Onabotulinumtoxin A (BTX-A) in treating children with neurogenic bladder (NB) secondary to myelomeningocele (MMC) with detrusor overactivity/low compliance. From January 2002 to June 2011, 47 patients out of 68 with neuropathic bladder were selected (22 females, 25 males, age range 5–17 years; mean age 10.7 years at first injection). They presented overactive/poor compliant neurogenic bladders on clean intermittent catheterization, and were resistant or non compliant to pharmacological therapy. Ten patients presented second to fourth grade concomitant monolateral/bilateral vesicoureteral reflux (VUR). All patients were incontinent despite catheterization. In the majority of patients Botulinum-A toxin was administered under general/local anesthesia by the injection of 200 IU of toxin, without exceeding the dosage of 12IU/kg body weight, diluted in 20 cc of saline solution in 20 sites, except in the periureteral areas. Follow-up included clinical and ultrasound examination, urodynamics performed at 6, 12 and 24 weeks, and annually thereafter. Seven patients remained stable, 21 patients required a second injection after 6–9 months and 19 a third injection. VUR was corrected, when necessary, in the same session after the BT-A injection, by 1–3 cc of subureteral Deflux®. Urodynamic parameters considered were leak point pressure (LPP), leak point volume (LPV) and specific volume at 20 cm H2O pressure. The results were analyzed using the Wilcoxon test. All patients experienced a significant 66.45% average increase of LPV (Wilcoxon paired rank test = 7169 × 10 −10) and a significant 118.57% average increase of SC 20 (Wilcoxon paired rank test = 2.466 × 10 −12). The difference between preoperative and postoperative LPP resulted not significant (Wilcoxon paired rank test = 0.8858) No patient presented severe systemic complications; 38/47 patients presented slight hematuria for 2–3 days. Two patients had postoperative urinary tract infection. All patients were hospitalized for 24 h with catheterization. Thirty-eight out of 47 patients achieved dryness between CIC; nine patients improved their incontinence but still need pads. Ten patients have resumed anticholinergic agents. Our results suggest that the use of BTX-A is safe and effective in patients with MMC with a positive effect on their dryness and quality of life. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)
Open AccessArticle Ochratoxin A Management in Vineyards by Lobesia botrana Biocontrol
Toxins 2013, 5(1), 49-59; doi:10.3390/toxins5010049
Received: 18 October 2012 / Revised: 19 December 2012 / Accepted: 21 December 2012 / Published: 2 January 2013
Cited by 4 | PDF Full-text (583 KB) | HTML Full-text | XML Full-text
Abstract
Grape berries attacked by Lobesia botrana larvae are more easily infected by Aspergillus section Nigri (black aspergilli) ochratoxigenic species. Two-year field trials were carried out in Apulia (Italy) to evaluate a bioinsecticide control strategy against L. botrana and the indirect effect on reducing
[...] Read more.
Grape berries attacked by Lobesia botrana larvae are more easily infected by Aspergillus section Nigri (black aspergilli) ochratoxigenic species. Two-year field trials were carried out in Apulia (Italy) to evaluate a bioinsecticide control strategy against L. botrana and the indirect effect on reducing ochratoxin A (OTA) contamination in vineyards. A commercial Bacillus thuringiensis formulate and an experimental Beauveria bassiana (ITEM-1559) formulate were tested in two vineyards cultivated with the same grape variety, Negroamaro, but with two different training systems (espalier and little-arbor techniques). In both years and training systems the treatments by B. bassiana ITEM-1559 significantly controlled L. botrana larvae attacks with effectiveness similar to B. thuringensis (more than 20%). A significant reduction of OTA concentrations (up to 80% compared to untreated controls) was observed only in the first year in both training systems, when the metereological parameters prior to harvest were more favorable to the insect attack. Results of field trials showed that B. bassiana ITEM-1559 is a valid bioinsecticide against L. botrana and that grape moth biocontrol is a strategy to reduce OTA contamination in vineyard in seasons with heavy natural infestation. Full article
(This article belongs to the Special Issue Ochratoxins 2011-2012)
Open AccessArticle First Evidence of Placental Transfer of Ochratoxin A in Horses
Toxins 2013, 5(1), 84-92; doi:10.3390/toxins5010084
Received: 17 October 2012 / Revised: 28 December 2012 / Accepted: 4 January 2013 / Published: 11 January 2013
Cited by 7 | PDF Full-text (203 KB) | HTML Full-text | XML Full-text
Abstract
Ochratoxin A (OTA) is a renal mycotoxin and transplacental genotoxic carcinogen. The aim of this study was to evaluate the natural occurrence of OTA in equine blood samples and its placental transfer. For the assessment of OTA levels, serum samples were collected from
[...] Read more.
Ochratoxin A (OTA) is a renal mycotoxin and transplacental genotoxic carcinogen. The aim of this study was to evaluate the natural occurrence of OTA in equine blood samples and its placental transfer. For the assessment of OTA levels, serum samples were collected from 12 stallions, 7 cycling mares and 17 pregnant mares. OTA was found in 83% of serum samples (median value = 121.4 pg/mL). For the assessment of placental transfer, serum samples were collected from the 17 mares after delivery and from the umbilical cords of their foals, after foaling. Fourteen serum samples from pregnant mares contained OTA (median value = 106.5 pg/mL), but only 50% of their foals were exposed (median values = 96.6 pg/mL). HPLC analysis carried out on four serum samples (collected from two mares and their respective foals) supported the ELISA results on OTA placental transfer. This is the first report on the natural occurrence of OTA in horse serum samples and placental transfer in horses. Full article
(This article belongs to the Special Issue Ochratoxins 2011-2012)
Open AccessArticle Influence of Botulinum Toxin Therapy on Postural Control and Lower Limb Intersegmental Coordination in Children with Spastic Cerebral Palsy
Toxins 2013, 5(1), 93-105; doi:10.3390/toxins5010093
Received: 17 September 2012 / Revised: 12 December 2012 / Accepted: 5 January 2013 / Published: 11 January 2013
Cited by 3 | PDF Full-text (581 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum toxin injections may significantly improve lower limb kinematics in gait of children with spastic forms of cerebral palsy. Here we aimed to analyze the effect of lower limb botulinum toxin injections on trunk postural control and lower limb intralimb (intersegmental) coordination in
[...] Read more.
Botulinum toxin injections may significantly improve lower limb kinematics in gait of children with spastic forms of cerebral palsy. Here we aimed to analyze the effect of lower limb botulinum toxin injections on trunk postural control and lower limb intralimb (intersegmental) coordination in children with spastic diplegia or spastic hemiplegia (GMFCS I or II). We recorded tridimensional trunk kinematics and thigh, shank and foot elevation angles in fourteen 3–12 year-old children with spastic diplegia and 14 with spastic hemiplegia while walking either barefoot or with ankle-foot orthoses (AFO) before and after botulinum toxin infiltration according to a management protocol. We found significantly greater trunk excursions in the transverse plane (barefoot condition) and in the frontal plane (AFO condition). Intralimb coordination showed significant differences only in the barefoot condition, suggesting that reducing the degrees of freedom may limit the emergence of selective coordination. Minimal relative phase analysis showed differences between the groups (diplegia and hemiplegia) but there were no significant alterations unless the children wore AFO. We conclude that botulinum toxin injection in lower limb spastic muscles leads to changes in motor planning, including through interference with trunk stability, but a combination of therapies (orthoses and physical therapy) is needed in order to learn new motor strategies. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)
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Open AccessArticle Difference in F-Actin Depolymerization Induced by Toxin B from the Clostridium difficile Strain VPI 10463 and Toxin B from the Variant Clostridium difficile Serotype F Strain 1470
Toxins 2013, 5(1), 106-119; doi:10.3390/toxins5010106
Received: 14 November 2012 / Revised: 14 December 2012 / Accepted: 28 December 2012 / Published: 11 January 2013
Cited by 6 | PDF Full-text (2810 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Clostridium difficile toxin A (TcdA) and toxin B (TcdB) are the causative agent of the C. difficile-associated diarrhea (CDAD) and its severe form, the pseudomembranous colitis (PMC). TcdB from the C. difficile strain VPI10463 mono-glucosylates (thereby inactivates) the small GTPases Rho, Rac,
[...] Read more.
Clostridium difficile toxin A (TcdA) and toxin B (TcdB) are the causative agent of the C. difficile-associated diarrhea (CDAD) and its severe form, the pseudomembranous colitis (PMC). TcdB from the C. difficile strain VPI10463 mono-glucosylates (thereby inactivates) the small GTPases Rho, Rac, and Cdc42, while Toxin B from the variant C. difficile strain serotype F 1470 (TcdBF) specifically mono-glucosylates Rac but not Rho(A/B/C). TcdBF is related to lethal toxin from C. sordellii (TcsL) that glucosylates Rac1 but not Rho(A/B/C). In this study, the effects of Rho-inactivating toxins on the concentrations of cellular F-actin were investigated using the rhodamine-phalloidin-based F-actin ELISA. TcdB induces F-actin depolymerization comparable to the RhoA-inactivating exoenzyme C3 from C. limosum (C3-lim). In contrast, the Rac-glucosylating toxins TcdBF and TcsL did not cause F-actin depolymerization. These observations led to the conclusion that F-actin depolymerization depends on the toxin’s capability of glucosylating RhoA. Furthermore, the integrity of focal adhesions (FAs) was analyzed using paxillin and p21-activated kinase (PAK) as FA marker proteins. Paxillin dephosphorylation was observed upon treatment of cells with TcdB, TcdBF, or C3-lim. In conclusion, the Rho-inactivating toxins induce loss of cell shape by either F-actin depolymerization (upon RhoA inactivation) or the disassembly of FAs (upon Rac1 inactivation). Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessArticle Bacillus anthracis Protective Antigen Kinetics in Inhalation Spore-Challenged Untreated or Levofloxacin/ Raxibacumab-Treated New Zealand White Rabbits
Toxins 2013, 5(1), 120-138; doi:10.3390/toxins5010120
Received: 23 July 2012 / Revised: 29 September 2012 / Accepted: 17 December 2012 / Published: 14 January 2013
Cited by 15 | PDF Full-text (460 KB) | HTML Full-text | XML Full-text
Abstract
Inhaled Bacillus anthracis spores germinate and the subsequent vegetative growth results in bacteremia and toxin production. Anthrax toxin is tripartite: the lethal factor and edema factor are enzymatic moieties, while the protective antigen (PA) binds to cell receptors and the enzymatic moieties. Antibiotics
[...] Read more.
Inhaled Bacillus anthracis spores germinate and the subsequent vegetative growth results in bacteremia and toxin production. Anthrax toxin is tripartite: the lethal factor and edema factor are enzymatic moieties, while the protective antigen (PA) binds to cell receptors and the enzymatic moieties. Antibiotics can control B. anthracis bacteremia, whereas raxibacumab binds PA and blocks lethal toxin effects. This study assessed plasma PA kinetics in rabbits following an inhaled B. anthracis spore challenge. Additionally, at 84 h post-challenge, 42% of challenged rabbits that had survived were treated with either levofloxacin/placebo or levofloxacin/raxibacumab. The profiles were modeled using a modified Gompertz/second exponential growth phase model in untreated rabbits, with added monoexponential PA elimination in treated rabbits. Shorter survival times were related to a higher plateau and a faster increase in PA levels. PA elimination half-lives were 10 and 19 h for the levofloxacin/placebo and levofloxacin/raxibacumab groups, respectively, with the difference attributable to persistent circulating PA-raxibacumab complex. PA kinetics were similar between untreated and treated rabbits, with one exception: treated rabbits had a plateau phase nearly twice as long as that for untreated rabbits. Treated rabbits that succumbed to disease had higher plateau PA levels and shorter plateau duration than surviving treated rabbits. Full article
(This article belongs to the Special Issue Anthrax Toxin)
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Open AccessArticle Effects of Ergot Alkaloids on Liver Function of Piglets as Evaluated by the 13C-Methacetin and 13C-α-Ketoisocaproic Acid Breath Test
Toxins 2013, 5(1), 139-161; doi:10.3390/toxins5010139
Received: 10 September 2012 / Revised: 12 December 2012 / Accepted: 20 December 2012 / Published: 15 January 2013
Cited by 4 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text
Abstract
Ergot alkaloids (the sum of individual ergot alkaloids are termed as total alkaloids, TA) are produced by the fungus Claviceps purpurea, which infests cereal grains commonly used as feedstuffs. Ergot alkaloids potentially modulate microsomal and mitochondrial hepatic enzymes. Thus, the aim of
[...] Read more.
Ergot alkaloids (the sum of individual ergot alkaloids are termed as total alkaloids, TA) are produced by the fungus Claviceps purpurea, which infests cereal grains commonly used as feedstuffs. Ergot alkaloids potentially modulate microsomal and mitochondrial hepatic enzymes. Thus, the aim of the present experiment was to assess their effects on microsomal and mitochondrial liver function using the 13C-Methacetin (MC) and 13C-α-ketoisocaproic acid (KICA) breath test, respectively. Two ergot batches were mixed into piglet diets, resulting in 11 and 22 mg (Ergot 5-low and Ergot 5-high), 9 and 14 mg TA/kg (Ergot 15-low and Ergot 15-high) and compared to an ergot-free control group. Feed intake and live weight gain decreased significantly with the TA content (p < 0.001). Feeding the Ergot 5-high diet tended to decrease the 60-min-cumulative 13CO2 percentage of the dose recovery (cPDR60) by 26% and 28% in the MC and KICA breath test, respectively, compared to the control group (p = 0.065). Therefore, both microsomal and mitochondrial liver function was slightly affected by ergot alkaloids. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessArticle Maize Aflatoxin Accumulation Segregates with Early Maturing Selections from an S2 Breeding Cross Population
Toxins 2013, 5(1), 162-172; doi:10.3390/toxins5010162
Received: 27 December 2012 / Revised: 9 January 2013 / Accepted: 9 January 2013 / Published: 15 January 2013
Cited by 2 | PDF Full-text (370 KB) | HTML Full-text | XML Full-text
Abstract
Maize breeders continue to seek new sources of aflatoxin resistance, but most lines identified as resistance sources are late maturing. The vast difference in flowering time makes it hard to cross these lines with proprietary commercial lines that mature much earlier and often
[...] Read more.
Maize breeders continue to seek new sources of aflatoxin resistance, but most lines identified as resistance sources are late maturing. The vast difference in flowering time makes it hard to cross these lines with proprietary commercial lines that mature much earlier and often subjects the reproductive phase of these resistant lines to the hottest and driest portion of the summer, making silking, pollination and grain fill challenging. Two hundred crosses from the GEM Project were screened for aflatoxin accumulation at Mississippi State in 2008, and a subset of these lines were screened again in 2009. The breeding cross UR13085:S99g99u was identified as a potential source of aflatoxin resistance, and maturity-based selections were made from an S2 breeding population from this same germplasm source: UR13085:S99g99u-B-B. The earliest maturing selections performed poorly for aflatoxin accumulation, but later maturing selections were identified with favorable levels of aflatoxin accumulation. These selections, while designated as “late” within this study, matured earlier than most aflatoxin resistant lines presently available to breeders. Two selections from this study, designated S5_L7 and S5_L8, are potential sources of aflatoxin resistance and will be advanced for line development and additional aflatoxin screening over more site years and environments. Full article
Open AccessArticle Carry-Over of Aflatoxin B1 to Aflatoxin M1 in High Yielding Israeli Cows in Mid- and Late-Lactation
Toxins 2013, 5(1), 173-183; doi:10.3390/toxins5010173
Received: 29 November 2012 / Revised: 31 December 2012 / Accepted: 7 January 2013 / Published: 16 January 2013
Cited by 15 | PDF Full-text (246 KB) | HTML Full-text | XML Full-text
Abstract
The potent hepatotoxin and carcinogen aflatoxin B1 (AFB1) is a common mycotoxin contaminant of grains used in animal feeds. Aflatoxin M1 (AFM1) is the major metabolite of AFB1 in mammals, being partially excreted into milk, and is a possible human carcinogen. The maximum
[...] Read more.
The potent hepatotoxin and carcinogen aflatoxin B1 (AFB1) is a common mycotoxin contaminant of grains used in animal feeds. Aflatoxin M1 (AFM1) is the major metabolite of AFB1 in mammals, being partially excreted into milk, and is a possible human carcinogen. The maximum permitted concentration of AFM1 in cows’ milk is 0.05 μg/kg in Israel and the European Union. Since milk yield and the carry-over of AFB1 in the feed to AFM1 in the milk are highly correlated, it was considered important to determine the AFM1 carry-over in Israeli-Holstein dairy cows, distinguished by world record high milk production. Twelve such cows were used to determine AFM1 carry-over following daily oral administration of feed containing ~86 μg AFB1 for 7 days. The mean carry-over rate at steady-state (Days 3–7) was 5.8% and 2.5% in mid-lactation and late-lactation groups, respectively. The carry-over appears to increase exponentially with milk yield and could be described by the equation: carry-over% = 0.5154 e0.0521 × milk yield, with r2 = 0.6224. If these data truly reflect the carry-over in the national Israeli dairy herd, the maximum level of AFB1 in feed should not exceed 1.4 μg/kg, a value 3.6 times lower than the maximum residue level currently applied in Israel. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
Open AccessCommunication Occurrence of Deoxynivalenol and Zearalenone in Commercial Fish Feed: An Initial Study
Toxins 2013, 5(1), 184-192; doi:10.3390/toxins5010184
Received: 18 October 2012 / Revised: 19 December 2012 / Accepted: 5 January 2013 / Published: 16 January 2013
Cited by 25 | PDF Full-text (184 KB) | HTML Full-text | XML Full-text
Abstract
The control of mycotoxins is a global challenge not only in human consumption but also in nutrition of farm animals including aquatic species. Fusarium toxins, such as deoxynivalenol (DON) and zearalenone (ZEN), are common contaminants of animal feed but no study reported the
[...] Read more.
The control of mycotoxins is a global challenge not only in human consumption but also in nutrition of farm animals including aquatic species. Fusarium toxins, such as deoxynivalenol (DON) and zearalenone (ZEN), are common contaminants of animal feed but no study reported the occurrence of both mycotoxins in fish feed so far. Here, we report for the first time the occurrence of DON and ZEN in samples of commercial fish feed designed for nutrition of cyprinids collected from central Europe. A maximal DON concentration of 825 μg kg−1 feed was found in one feed whereas average values of 289 μg kg−1 feed were noted. ZEN was the more prevalent mycotoxin but the concentrations were lower showing an average level of 67.9 μg kg−1 feed. Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed)
Open AccessArticle Removal of Toxin (Tetrodotoxin) from Puffer Ovary by Traditional Fermentation
Toxins 2013, 5(1), 193-202; doi:10.3390/toxins5010193
Received: 12 December 2012 / Revised: 10 January 2013 / Accepted: 11 January 2013 / Published: 18 January 2013
Cited by 2 | PDF Full-text (480 KB) | HTML Full-text | XML Full-text
Abstract
The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented “Nukazuke and “Kasuzuke ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (I
[...] Read more.
The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented “Nukazuke and “Kasuzuke ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (INa) recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in “Nukazuke” and “Kasuzuke ovaries decreased to 1/50–1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes” fresh muscle that is normally eaten. It was concluded that the fermented “Nukazuke and “Kasuzuke” ovaries of puffer fish T. Stictonotus are safe and harmless as food. Full article
(This article belongs to the Special Issue Toxins from Aquatic Organisms)
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Review

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Open AccessReview Prevalence, Biogenesis, and Functionality of the Serine Protease Autotransporter EspP
Toxins 2013, 5(1), 25-48; doi:10.3390/toxins5010025
Received: 25 October 2012 / Revised: 18 December 2012 / Accepted: 21 December 2012 / Published: 28 December 2012
Cited by 5 | PDF Full-text (1333 KB) | HTML Full-text | XML Full-text
Abstract
Enterohemorrhagic E. coli (EHEC) causes severe diseases in humans worldwide. One of its virulence factors is EspP, which belongs to the serine protease autotransporters of Enterobacteriaceae (SPATE) family. In this review we recapitulate the current data on prevalence, biogenesis, structural properties and
[...] Read more.
Enterohemorrhagic E. coli (EHEC) causes severe diseases in humans worldwide. One of its virulence factors is EspP, which belongs to the serine protease autotransporters of Enterobacteriaceae (SPATE) family. In this review we recapitulate the current data on prevalence, biogenesis, structural properties and functionality. EspP has been used to investigate mechanistic details of autotransport, and recent studies indicate that this transport mechanism is not autonomous but rather dependent on additional factors. Currently, five subtypes have been identified (EspPα-EspPε), with EspPα being associated with highly virulent EHEC serotypes and isolates from patients with severe disease. EspPα has been shown to degrade major proteins of the complement cascade, namely C3 and C5 and probably interferes with hemostasis by cleavage of coagulation factor V. Furthermore, EspPα is believed to contribute to biofilm formation perhaps by polymerization to rope-like structures. Together with the proteolytic activity, EspPα might ameliorate host colonization and interfere with host response. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessReview Off Label Use of Botulinum Toxin in Children under Two Years of Age: A Systematic Review
Toxins 2013, 5(1), 60-72; doi:10.3390/toxins5010060
Received: 30 September 2012 / Revised: 14 December 2012 / Accepted: 24 December 2012 / Published: 7 January 2013
Cited by 9 | PDF Full-text (201 KB) | HTML Full-text | XML Full-text
Abstract
The treatment of children with cerebral palsy with Botulinum Toxin is considered safe and effective, but is only approved for children older than two years of age. The effect of BoNT-A injection on juvenile skeletal muscle especially on neuromuscular junction density, distribution and
[...] Read more.
The treatment of children with cerebral palsy with Botulinum Toxin is considered safe and effective, but is only approved for children older than two years of age. The effect of BoNT-A injection on juvenile skeletal muscle especially on neuromuscular junction density, distribution and morphology is poorly delineated and concerns of irreversible damage to the motor endplates especially in young children exist. In contrast, earlier treatment could be appropriate to improve the attainment of motor milestones and general motor development. This review systematically analyzes the evidence regarding this hypothesis. A database search, including PubMed and Medline databases, was performed and all randomized controlled trials (RCTs) comparing the efficacy of Botulinum Toxin in children younger than two years were identified. Two authors independently extracted the data and the methods of all identified trials were assessed. Three RCTs met the inclusion criteria. The results of the analysis revealed an improvement in spasticity of the upper and lower extremities as well as in the range of motion in the joints of the lower limbs. However, evidence of an improvement of general motor development could not be found, as the assessment of this area was not completely specified for this patient group. Based on available evidence it can not be concluded that Botulinum Toxin treatment in children younger than two years improves the achievement of motor milestones. However, there is evidence for the reduction of spasticity, avoiding contractures and delaying surgery. Due to some limitations, the results of this review should be cautiously interpreted. More studies, long-term follow up independent high-quality RCTs with effectiveness analyses are needed. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)
Open AccessReview Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms
Toxins 2013, 5(1), 73-83; doi:10.3390/toxins5010073
Received: 26 September 2012 / Revised: 25 December 2012 / Accepted: 27 December 2012 / Published: 8 January 2013
Cited by 16 | PDF Full-text (183 KB) | HTML Full-text | XML Full-text
Abstract
Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals,
[...] Read more.
Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection. Full article
(This article belongs to the Special Issue Clinical Use of Botulinum Toxins)

Other

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Open AccessBrief Report The Receptors that Mediate the Direct Lethality of Anthrax Toxin
Toxins 2013, 5(1), 1-8; doi:10.3390/toxins5010001
Received: 24 November 2012 / Revised: 19 December 2012 / Accepted: 21 December 2012 / Published: 27 December 2012
Cited by 13 | PDF Full-text (329 KB) | HTML Full-text | XML Full-text
Abstract
Tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2) are the two well-characterized anthrax toxin receptors, each containing a von Willebrand factor A (vWA) domain responsible for anthrax protective antigen (PA) binding. Recently, a cell-based analysis was used to implicate another vWA domain-containing
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Tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2) are the two well-characterized anthrax toxin receptors, each containing a von Willebrand factor A (vWA) domain responsible for anthrax protective antigen (PA) binding. Recently, a cell-based analysis was used to implicate another vWA domain-containing protein, integrin β1 as a third anthrax toxin receptor. To explore whether proteins other than TEM8 and CMG2 function as anthrax toxin receptors in vivo, we challenged mice lacking TEM8 and/or CMG2. Specifically, we used as an effector protein the fusion protein FP59, a fusion between the PA-binding domain of anthrax lethal factor (LF) and the catalytic domain of Pseudomonas aeruginosa exotoxin A. FP59 is at least 50-fold more potent than LF in the presence of PA, with 2 μg PA + 2 μg FP59 being sufficient to kill a mouse. While TEM8−/− and wild type control mice succumbed to a 5 μg PA + 5 μg FP59 challenge, CMG2−/− mice were completely resistant to this dose, confirming that CMG2 is the major anthrax toxin receptor in vivo. To detect whether any toxic effects are mediated by TEM8 or other putative receptors such as integrin β1, CMG2−/−/TEM8−/− mice were challenged with as many as five doses of 50 μg PA + 50 μg FP59. Strikingly, the CMG2−/−/TEM8−/− mice were completely resistant to the 5-dose challenge. These results strongly suggest that TEM8 is the only minor anthrax toxin receptor mediating direct lethality in vivo and that other proteins implicated as receptors do not play this role. Full article
(This article belongs to the Special Issue Anthrax Toxin)

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