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A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: closed (31 October 2009)

Special Issue Editor

Editor-in-Chief
Prof. Dr. Med. Florian Lang

Physiologisches Institut I, Universität Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany
Website | E-Mail
Fax: +49 (0)7071 29 5618
Interests: mechanisms and clinical significance of cell volume regulation; erythrocyte death signaling; serum-and glucocorticoid inducible kinase isoforms; physiology and pharmacology of human ion channels and carriers expressed in oocytes; host cell physiology in hostpathogen interaction; mechanisms of apoptotic cell death

Published Papers (7 papers)

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Research

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Open AccessArticle The Effects of Cholera Toxin on Cellular Energy Metabolism
Toxins 2010, 2(4), 632-648; doi:10.3390/toxins2040632
Received: 11 March 2010 / Revised: 31 March 2010 / Accepted: 6 April 2010 / Published: 8 April 2010
Cited by 12 | PDF Full-text (2338 KB) | HTML Full-text | XML Full-text
Abstract
Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate
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Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate production and a decrease in the oxygen uptake. We believe the responses observed are due to a CTx-induced activation of adenylate cyclase, increasing cAMP production and resulting in a switch to anaerobic respiration. Inhibitors (H-89, brefeldin A) and stimulators (forskolin) of cAMP were employed to modulate the CTx-induced cAMP responses. The results of this study show the utility of multianalyte microphysiometry to quantitatively determine the dynamic metabolic effects of toxins and affected pathways. Full article
(This article belongs to the Special Issue Feature Papers)
Open AccessArticle Effects of Aflatoxin B1 and Fumonisin B1 on Blood Biochemical Parameters in Broilers
Toxins 2010, 2(4), 453-460; doi:10.3390/toxins2040453
Received: 4 March 2010 / Revised: 16 March 2010 / Accepted: 26 March 2010 / Published: 29 March 2010
Cited by 8 | PDF Full-text (274 KB) | HTML Full-text | XML Full-text
Abstract
The individual and combined effects of dietary aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days
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The individual and combined effects of dietary aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB1 (0, 50 and 200 μg AFB1/kg), and three levels of FB1 (0, 50 and 200 mg FB1/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB1 only, concentrations of AST were higher (p < 0.05) in all other treatment groups when compared with controls. Plasma TP was lower (p < 0.05) at six days post feeding in groups fed 200 mgAFB1/kg alone or in combination with FB1. At day 33 days post feeding, with the exception of birds fed the highest combination of AFB1 and FB1 which had higher plasma TP than control birds, plasma TP of birds fed other dietary treatments were similar to controls. Broilers receiving the highest levels of AFB1 and FB1 had bile duct proliferation and trabecular disorder in liver samples. AFB1 singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST. Full article
(This article belongs to the Special Issue Feature Papers)
Open AccessArticle Determination of the Biological Activity and Structure Activity Relationships of Drugs Based on the Highly Cytotoxic Duocarmycins and CC-1065
Toxins 2009, 1(2), 134-150; doi:10.3390/toxins1020134
Received: 3 November 2009 / Revised: 28 November 2009 / Accepted: 1 December 2009 / Published: 2 December 2009
Cited by 12 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
The natural antibiotics CC-1065 and the duocarmycins are highly cytotoxic compounds which however are not suitable for cancer therapy due to their general toxicity. We have developed glycosidic prodrugs of seco-analogues of these antibiotics for a selective cancer therapy using conjugates of
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The natural antibiotics CC-1065 and the duocarmycins are highly cytotoxic compounds which however are not suitable for cancer therapy due to their general toxicity. We have developed glycosidic prodrugs of seco-analogues of these antibiotics for a selective cancer therapy using conjugates of glycohydrolases and tumour-selective monoclonal antibodies for the liberation of the drugs from the prodrugs predominantly at the tumour site. For the determination of structure activity relationships of the different seco-drugs, experiments addressing their interaction with synthetic DNA were performed. Using electrospray mass spectrometry and high performance liquid chromatography, the experiments revealed a correlation of the stability of these drugs with their cytotoxicity in cell culture investigations. Furthermore, it was shown that the drugs bind to AT-rich regions of double-stranded DNA and the more cytotoxic drugs induce DNA fragmentation at room temperature in several of the selected DNA double-strands. Finally, an explanation for the very high cytotoxicity of CC-1065, the duocarmycins and analogous drugs is given. Full article
(This article belongs to the Special Issue Feature Papers)
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Open AccessArticle Oxazolone-Induced Delayed Type Hypersensitivity Reaction in the Adult Yucatan Pigs. A Useful Model for Drug Development and Validation
Toxins 2009, 1(1), 25-36; doi:10.3390/toxins1010025
Received: 29 July 2009 / Revised: 19 August 2009 / Accepted: 21 August 2009 / Published: 21 August 2009
PDF Full-text (368 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of this study was to establish a model of delayed type hypersensitivity (DTH) reaction in the ear skin of large animals such as adult Yucatan pigs, which may aid in evaluating the efficacy of therapeutic modalities of newly developed anti-inflammatory drugs.
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The purpose of this study was to establish a model of delayed type hypersensitivity (DTH) reaction in the ear skin of large animals such as adult Yucatan pigs, which may aid in evaluating the efficacy of therapeutic modalities of newly developed anti-inflammatory drugs. The pigs were sensitized with oxazolone, re-challenged with the same irritant six days later, and dosed with either vehicle or with cyclosporine A (CsA) before and after challenge. CsA reduced the redness, inhibited the accumulation of ear fluid and inflammatory cells, as well as the release of the inflammatory mediators. Further, CsA inhibited the proliferation of T cells collected from the spleens or PBMCs of CsA-treated pigs when these cells were stimulated in vitro with PMA plus Ionomycin. These results indicate that pig skin can be used to evaluate modalities for the purpose of developing drugs that may be used to treat DTH in humans. Full article
(This article belongs to the Special Issue Feature Papers)
Open AccessArticle Effect of Neem Leaf Extract and Neem Oil on Penicillium Growth, Sporulation, Morphology and Ochratoxin A Production
Toxins 2009, 1(1), 3-13; doi:10.3390/toxins1010003
Received: 18 June 2009 / Revised: 14 July 2009 / Accepted: 21 July 2009 / Published: 23 July 2009
Cited by 10 | PDF Full-text (404 KB) | HTML Full-text | XML Full-text
Abstract
In vitro trials were conducted to evaluate the effect of Azadirachta indica (neem) extracts on mycelial growth, sporulation, morphology and ochratoxin A production by P. verrucosum and P. brevicompactum. The effect of neem oil extract from seeds and leaf was evaluated at
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In vitro trials were conducted to evaluate the effect of Azadirachta indica (neem) extracts on mycelial growth, sporulation, morphology and ochratoxin A production by P. verrucosum and P. brevicompactum. The effect of neem oil extract from seeds and leaf was evaluated at 0.125; 0.25 and 0.5% and 6.25 and 12.5 mg/mL, respectively, in Yeast Extract Sucrose (YES) medium. Ochratoxin A production was evaluated by a thin-layer chromatography technique. Oil extracts exhibited significant (p ≤ 0.05) reduction of growth and sporulation of the fungi. No inhibition of ochratoxin A production was observed. Given its accessibility and low cost, neem oil could be implemented as part of a sustainable integrated pest management strategy for plant disease, as it has been shown to be fungitoxic by inhibition of growth and sporulation. Full article
(This article belongs to the Special Issue Feature Papers)

Review

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Open AccessReview Cyclopiazonic Acid Biosynthesis of Aspergillus flavus and Aspergillus oryzae
Toxins 2009, 1(2), 74-99; doi:10.3390/toxins1020074
Received: 9 October 2009 / Revised: 3 November 2009 / Accepted: 4 November 2009 / Published: 6 November 2009
Cited by 31 | PDF Full-text (512 KB) | HTML Full-text | XML Full-text
Abstract
Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by some of the same strains of A. flavus that produce aflatoxins and by some Aspergillus oryzae strains. Despite its discovery 40 years ago, few reviews of its toxicity and biosynthesis have been reported.
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Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by some of the same strains of A. flavus that produce aflatoxins and by some Aspergillus oryzae strains. Despite its discovery 40 years ago, few reviews of its toxicity and biosynthesis have been reported. This review examines what is currently known about the toxicity of CPA to animals and humans, both by itself or in combination with other mycotoxins. The review also discusses CPA biosynthesis and the genetic diversity of CPA production in A. flavus/oryzae populations. Full article
(This article belongs to the Special Issue Feature Papers)
Open AccessReview Predicted Roles of the Uncharacterized Clustered Genes in Aflatoxin Biosynthesis
Toxins 2009, 1(1), 37-58; doi:10.3390/toxins1010037
Received: 11 August 2009 / Revised: 22 September 2009 / Accepted: 24 September 2009 / Published: 25 September 2009
Cited by 13 | PDF Full-text (1112 KB) | HTML Full-text | XML Full-text
Abstract
Biosynthesis of the toxic and carcinogenic aflatoxins (AFs) requires the activity of more than 27 enzymes. The roles in biosynthesis of newly described enzymes are discussed in this review. We suggest that HypC catalyzes the oxidation of norsolorinic acid anthrone; AvfA (AflI), the
[...] Read more.
Biosynthesis of the toxic and carcinogenic aflatoxins (AFs) requires the activity of more than 27 enzymes. The roles in biosynthesis of newly described enzymes are discussed in this review. We suggest that HypC catalyzes the oxidation of norsolorinic acid anthrone; AvfA (AflI), the ring-closure step in formation of hydroxyversicolorone; HypB, the second oxidation step in conversion of O-methylsterigmatocystin to AF; and HypE and NorA (AflE), the final two steps in AFB1 formation. HypD, an integral membrane protein, affects fungal development and lowers AF production while AflJ (AflS), has a partial methyltransferase domain that may be important in its function as a transcriptional co-activator. Full article
(This article belongs to the Special Issue Feature Papers)
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