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Jane E. Harding - One of the best experts on this subject based on the ideXlab platform.
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Effect of Sporidesmin-induced liver damage in ewes before mating on growth of the foetus and placenta
World Mycotoxin Journal, 2009Co-Authors: Mark H. Oliver, Jane E. HardingAbstract:Sporidesmin is a fungal toxin commonly found in pasture. It causes liver damage in sheep that resembles cholestasis in humans. We determined whether pre-mating Sporidesmin-induced liver damage in ewes might provide a useful approach to the experimental induction of intrauterine growth restriction (IUGR). Romney ewes were drenched with Sporidesmin extracts. Affected ewes (SP, n=44) and controls (CN, n=42) were mated. Sporidesmin treatment decreased pregnancy rate (non-pregnant; SP 43% vs. CN 12%, twin; SP 23% vs. CN 52%, both P
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effect of Sporidesmin induced liver damage in ewes before mating on growth of the foetus and placenta
World Mycotoxin Journal, 2009Co-Authors: Mark H. Oliver, Jane E. HardingAbstract:Sporidesmin is a fungal toxin commonly found in pasture. It causes liver damage in sheep that resembles cholestasis in humans. We determined whether pre-mating Sporidesmin-induced liver damage in ewes might provide a useful approach to the experimental induction of intrauterine growth restriction (IUGR). Romney ewes were drenched with Sporidesmin extracts. Affected ewes (SP, n=44) and controls (CN, n=42) were mated. Sporidesmin treatment decreased pregnancy rate (non-pregnant; SP 43% vs. CN 12%, twin; SP 23% vs. CN 52%, both P<0.05). SP foetuses were 6% lighter than CN foetuses at 89 days of gestation, but not at 134 days. Increasing maternal plasma gamma glutamyl transferase activities at mating were associated at 89 days with reduced maternal weight (-1.1: -1.9, -0.3 kg/100 U/l, mean effect size: 95% confidence intervals), increased visual liver damage and reduced placentome number (-1.4: -2.7, -0.1/100 U/l) and foetal pancreatic weight (-21: -38, -4 mg/100 U/l). They were also associated at 134 days wi...
Neale R. Towers - One of the best experts on this subject based on the ideXlab platform.
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A zinc-containing intraruminal device for prevention of the Sporidesmin-induced cholangiopathy of facial eczema in calves.
New Zealand Veterinary Journal, 2001Co-Authors: Rex Munday, Neale R. Towers, A.m. Thompson, Barry L. Smith, K. O'donnell, R.m. Mcdonald, M. StirnemannAbstract:Abstract Aim: To develop and evaluate a zinc-containing intraruminal controlled-release bolus for protection of calves (175 – 250 kg bodyweight) against facial eczema (FE). Methods: Boluses releasing zinc, in the form of zinc oxide, at rates ranging from 1.67 to 4.25 g/day were administered to calves which were challenged 4 weeks later with the FE toxin, Sporidesmin. The efficacy of the boluses in protecting against Sporidesmin-induced cholangiopathy was determined by measuring serum activities of gamma-glutamyltransferase (GGT). Results: A bolus releasing zinc at approximately 4.25 g/day gave excellent protection against Sporidesmin toxicity for periods of up to 5 weeks duration. Conclusions: This zinc-containing intraruminal controlled-release bolus has the potential to markedly reduce the incidence and severity of FE in calves within a 175 – 250 kg bodyweight range.
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Urinary excretion of immunoreactive Sporidesmin metabolites in sheep in relation to factors influencing susceptibility to Sporidesmin intoxication
New Zealand Veterinary Journal, 1999Co-Authors: B.l. Smith, L. R. Briggs, P. P. Embling, Allan D. Hawkes, Neale R. TowersAbstract:Abstract Aim. To study the urinary disposition of orally administered Sporidesmins A and D in sheep and identify factors influencing their kinetics, particularly the influence of breeding for resistance and susceptibility to Sporidesmin, the mycotoxin responsible for the hepatogenous photosensitisation, facial eczema. Methods. A competitive ELISA was used to monitor urinary output of immunoreactive metabolites after the intraruminal administration, tofemale Romney sheep,of either Sporidesmin A or Sporidesmin D, the nontoxic analogue. Preliminary characterisation of metabolites was carried out using HPLC with fractions monitored by ELISA. Results. Maximum urinary excretion rates of immunoreactive metabolites occurred 2–8 h after dosing with Sporidesmin D and 15–30 h after dosing with Sporidesmin A. Sporidesmin D caused no liver injury, as detected by changes in serum enzyme activity, while the liver injury caused by Sporidesmin A was greatest for the sheep with the highest cumulative output of metabolite. ...
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Development of immunodiagnostic field tests for the detection of the mycotoxin, Sporidesmin a
Food and Agricultural Immunology, 1998Co-Authors: Roger Collin, Lyn R. Briggs, Elisabeth Schneider, Neale R. TowersAbstract:Three rapid immunoassays—immunofiltration, immunochromatography and dipstick—were developed for the detection of Sporidesmin A, the mycotoxin responsible for facial eczema’, a disease which causes liver injury and photosensitization of livestock in New Zealand. Each assay format exhibited particular advantages and disadvantages with regard to assay sensitivity, working range and ease of use. The immunofiltration assay proved to be suitable for the detection of Sporidesmin A in pasture due to its sensitivity and its potential to be used outside a laboratory environment. Semi‐quantitative scores of spiked pasture samples using the immunofiltration assay were in good agreement with the amount of Sporidesmin A added to the samples.
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Lack of toxicity of a non-Sporidesmin-producing strain of Pithomyces chartarum in cell culture and when dosed to lambs.
New Zealand Veterinary Journal, 1996Co-Authors: R. G. Collin, B.l. Smith, Neale R. TowersAbstract:In New Zealand the fungus Pithomyces charturum normally produces Sporidesmin, a mycotoxin, which is responsible for the hepatogenous photosensitisation disease known as facial eczema. Cultures from an isolate of P. charturum, which does not produce Sporidesmin, were examined by cell culture and by dosing to lambs to determine whether other toxic metabolites were produced. Acute and long term toxicity studies were conducted with the toxic response being assessed by weight changes, postmortem and histological examination of tissues, blood biochemistry and haematology tests. An extract from a Sporidesmin-producing isolate was highly toxic in cell culture, while extracts of the nonSporidesmin-producing isolate did not cause a cytotoxic response to HEp 2 cells. After dosing with a Sporidesmin-producing isolate, lambs developed liver lesions and clinical signs of facial eczema. Serum biochemistry changes occurred which were consistent with Sporidesmin poisoning. Lambs dosed with the nonSporidesmin-producing isolate, at the rate of thirty times the number of spores of the Sporidesmin-producing isolate, showed no observable toxic effects. All organs were of normal appearance, and histological examination of tissues, blood biochemistry and haematology results showed no abnormal changes. Similarly, long term dosing of extracts of the nonSporidesmin-producing isolate, at a rate equivalent to 100,000 spores/g of grass, produced no indication of a toxic response. It was concluded that the nonSporidesmin-producing isolate of P. churtarum contained no toxic metabolites in significant concentration.
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Development and evaluation of an enzyme immunoassay for Sporidesmin in pasture
New Zealand Journal of Agricultural Research, 1995Co-Authors: Roger Collin, Lyn R. Briggs, Neale R. TowersAbstract:Abstract An enzyme immunoassay was developed which could detect Sporidesmin in pasture samples. The assay had a linear working range of 0.4–40 ng/ml Sporidesmin A while validation using pasture extracts gave mean percentage recoveries of 124% for samples containing 1 ng/ml Sporidesmin and 97% for extracts containing 20 ng/ml Sporidesmin. The Sporidesmin levels and numbers of Pithomyces chartarum spores from many pasture samples were compared. The amount of Sporidesmin detected generally corresponded to the number of spores found in the sample.
Mark H. Oliver - One of the best experts on this subject based on the ideXlab platform.
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Effect of Sporidesmin-induced liver damage in ewes before mating on growth of the foetus and placenta
World Mycotoxin Journal, 2009Co-Authors: Mark H. Oliver, Jane E. HardingAbstract:Sporidesmin is a fungal toxin commonly found in pasture. It causes liver damage in sheep that resembles cholestasis in humans. We determined whether pre-mating Sporidesmin-induced liver damage in ewes might provide a useful approach to the experimental induction of intrauterine growth restriction (IUGR). Romney ewes were drenched with Sporidesmin extracts. Affected ewes (SP, n=44) and controls (CN, n=42) were mated. Sporidesmin treatment decreased pregnancy rate (non-pregnant; SP 43% vs. CN 12%, twin; SP 23% vs. CN 52%, both P
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effect of Sporidesmin induced liver damage in ewes before mating on growth of the foetus and placenta
World Mycotoxin Journal, 2009Co-Authors: Mark H. Oliver, Jane E. HardingAbstract:Sporidesmin is a fungal toxin commonly found in pasture. It causes liver damage in sheep that resembles cholestasis in humans. We determined whether pre-mating Sporidesmin-induced liver damage in ewes might provide a useful approach to the experimental induction of intrauterine growth restriction (IUGR). Romney ewes were drenched with Sporidesmin extracts. Affected ewes (SP, n=44) and controls (CN, n=42) were mated. Sporidesmin treatment decreased pregnancy rate (non-pregnant; SP 43% vs. CN 12%, twin; SP 23% vs. CN 52%, both P<0.05). SP foetuses were 6% lighter than CN foetuses at 89 days of gestation, but not at 134 days. Increasing maternal plasma gamma glutamyl transferase activities at mating were associated at 89 days with reduced maternal weight (-1.1: -1.9, -0.3 kg/100 U/l, mean effect size: 95% confidence intervals), increased visual liver damage and reduced placentome number (-1.4: -2.7, -0.1/100 U/l) and foetal pancreatic weight (-21: -38, -4 mg/100 U/l). They were also associated at 134 days wi...
Peter J. Derrick - One of the best experts on this subject based on the ideXlab platform.
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Effect of a one-off Sporidesmin challenge on the milk production of dairy cows.
New Zealand Veterinary Journal, 2018Co-Authors: Zoe M. Matthews, Mark G. Collett, Jonathan C. Marshall, Peter J. Derrick, Ashton Partridge, Patrick J. B. EdwardsAbstract:To investigate the effects on milk yield in lactating dairy cows of a single dose of Sporidesmin, and to categorise the responses based on clinical signs and differing degrees of liver damage, as a...
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Serum metabolomics using ultra performance liquid chromatography coupled to mass spectrometry in lactating dairy cows following a single dose of Sporidesmin
Metabolomics, 2018Co-Authors: Zoe M. Matthews, Patrick J. B. Edwards, Ariane Kahnt, Mark G. Collett, Jonathan C. Marshall, Ashton C. Partridge, Scott J. Harrison, Karl Fraser, Mingshu Cao, Peter J. DerrickAbstract:Introduction Photosensitization is a common clinical sign in cows suffering from liver damage caused by the mycotoxin Sporidesmin. This disease, called facial eczema (FE), is of major importance in New Zealand. Current techniques for diagnosing animals with subclinical Sporidesmin-induced liver damage (i.e. without photosensitization) are nonspecific. In addition, little is known of the mechanisms involved in Sporidesmin resistance, nor the early effects seen following low-dose Sporidesmin intoxication. Objective The objective of this study was to identify individual metabolites or metabolic profiles that could be used as serum markers for early stage FE in lactating cows. Methods Results are presented from a 59-day Sporidesmin challenge in Friesian-cross dairy cows. Serum metabolite profiles were obtained using reversed phase ultra-performance liquid chromatography (UPLC) electrospray ionization mass spectrometry (MS) and UPLC tandem MS. Multivariate and time series analyses were used to assess the data. Results Statistical analysis, both with and without the temporal component, could distinguish the profiles of animals with clinical signs from the others, but not those affected subclinically. An increase in the concentrations of a combination of taurine- and glycine-conjugated secondary bile acids (BAs) was the most likely cause of the separation. This is the first time that MS methods have been applied to FE and that bile acids changes have been detected in cattle exposed to Sporidesmin. Conclusions It is well known that BA concentrations increase during cholestasis due to damage to bile ducts and leakage of the bile. This is the first study to investigate metabolomic changes in serum following a Sporidesmin challenge. Further work to establish the significance of the elevation of individual BAs concentrations in the serum of early-stage Sporidesmin-poisoned cows is necessary.
Tw Jordan - One of the best experts on this subject based on the ideXlab platform.
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The cellular and molecular toxicity of Sporidesmin.
New Zealand Veterinary Journal, 2020Co-Authors: Tw JordanAbstract:The fungal metabolite Sporidesmin is responsible for the hepatogenous photosensitising disease facial eczema in livestock. Toxicity is due to a sulfur-bridged epidithiodioxopiperazine ring that has...
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Effects of Sporidesmin on cultured biliary tract cells from Romney lambs that differed in their sensitivity to Sporidesmin.
New Zealand Veterinary Journal, 2018Co-Authors: G C Lindsay, C. A. Morris, M Boucher, K Capundan, Tw JordanAbstract:AIMSTo investigate the effects of Sporidesmin on cells cultured from the epithelial surface of sheep gallbladder walls, and to examine cellular responses to Sporidesmin using cultures prepared from the gallbladders of sheep from selection lines that differed in sensitivity to Sporidesmin-induced liver damage.METHODSGallbladders were obtained following slaughter of lambs that were selected for resistance or susceptibility to Sporidesmin-induced liver damage, or were not selected (controls). Monolayer cell cultures were established after incubation of excised gallbladders with protease to detach the lining epithelial cells from the muscular and connective tissue of the gallbladder wall. Released cells were harvested and transferred to culture flasks or dishes, then incubated with 1 µg/mL Sporidesmin and were examined at 5 minute intervals, up to 3 hours, using light microscopy to monitor loss of attachment of cultured cells. Immunofluorescence staining of cell cultures was used to identify cytokeratin 19 as...
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Effects of Sporidesmin on cultured biliary tract cells from Romney lambs that differed in their sensitivity to Sporidesmin
2018Co-Authors: G C Lindsay, C. A. Morris, M Boucher, K Capundan, Tw JordanAbstract:To investigate the effects of Sporidesmin on cells cultured from the epithelial surface of sheep gallbladder walls, and to examine cellular responses to Sporidesmin using cultures prepared from the gallbladders of sheep from selection lines that differed in sensitivity to Sporidesmin-induced liver damage. Gallbladders were obtained following slaughter of lambs that were selected for resistance or susceptibility to Sporidesmin-induced liver damage, or were not selected (controls). Monolayer cell cultures were established after incubation of excised gallbladders with protease to detach the lining epithelial cells from the muscular and connective tissue of the gallbladder wall. Released cells were harvested and transferred to culture flasks or dishes, then incubated with 1 µg/mL Sporidesmin and were examined at 5 minute intervals, up to 3 hours, using light microscopy to monitor loss of attachment of cultured cells. Immunofluorescence staining of cell cultures was used to identify cytokeratin 19 as a marker for biliary epithelial cells, and to characterise Sporidesmin-induced change in the cellular distribution of actin microfilaments. Gallbladder size was also measured. In cultures incubated with Sporidesmin, cells at the margins of sheets of cells showed the first signs of change, becoming unanchored from the culture vessels while remaining attached to the cell mass. This was followed by progressive detachment of sheets of cells and clumps of rounded cells. Disruption of cytoplasmic actin microfilaments with accumulation of actin in the cytoplasm adjacent to the plasma membrane preceded major detachment of cells. Cells from susceptible line lambs were extensively rounded up within 1 hour with complete or almost complete detachment within 2 hours, whereas cultures from resistant line lambs generally only contained detaching rounded-up cells at the periphery of monolayers within 2 hours; detachment observed in cells from the control line lambs was intermediate. There was a trend for gallbladders to be smaller in male lambs from the resistant line compared to the control or susceptible lines. Altered cell adhesion and disruption of microfilament actin in biliary cell cultures incubated with Sporidesmin suggest that biliary tract pathology may be due to the effects of the toxin on cytoplasmic and cell surface protein networks that affect the integrity of the epithelial lining of the biliary tract. These effects can be interpreted in terms of the hepatobiliary pathology of facial eczema, including potential differences in sensitivity of biliary tract cells that may contribute to inherited resistance and susceptibility to Sporidesmin and hence facial eczema.
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Use of indirect immunofluorescence to show changes in liver actin microfilament staining in inbred mice strains exposed to the mycotoxin Sporidesmin
Liver, 2008Co-Authors: Tw JordanAbstract:— The distribution of microfilaments in cryostat sections of liver from BALB/c and C57BL/6 mice was compared using the F-actin binding probe rhodaminyl phalloidin and indirect immunofluorescence using a human serum containing anti-actin autoantibodies. The immunological reactivity of this serum was established by its capacity to immunoprecipitate purified skeletal muscle actin and by its ability to immunoprecipitate a protein which migrated electrophoretically with actin from 35S-labeled liver cells. Oral administration of the liver toxin Sporidesmin did not substantially alter the binding of rhodaminyl phalloidin to microfilaments but the reactivity of the anti-actin serum with the liver cytoskeleton was diminished 3 h after, and enhanced within 24 h of toxin ingestion. Amounts of actin measured by DNAase inhibition were not altered. The results are assessed in terms of their significance for understanding the way in which Sporidesmin causes liver damage.
