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1.
Sixteen pairs of identical twin dairy calves were reared together and at one year of age subjected to a test of uniformity of response to sporidesmin intoxication. The response was measured by scoring livers for toxic injury and by measuring serum gamma-glutamyltransferase at weekly intervals after dosing. Within pair variance in serum gamma-glutamyltransferase was greatest at two and six weeks after sporidesmin dosing when enzyme levels were rising and falling. Within twin variance and the interclass correlation coefficients were least and greatest respectively at five weeks after dosing. At five weeks the GGT correlation coefficient was 0.89 and for liver injury score 0.76. High consistency among twins of a pair, compared with differences among pairs indicates a high relative efficiency in using identical twins rather than singles for experimental work (approximately x 5). It is also consistent with a high heritability of resistance to sporidesmin intoxication in dairy cattle. 相似文献
2.
No liver damage occurred in a group of 21 lambs dosed intraruminally with up to 9 g of sarsasapogenin or diosgenin daily for 10 consecutive days. In contrast, seven out of 15 lambs dosed with 0.1 mg of sporidesmin/kg liveweight in combination with sarsasapogenin and three out of six lambs dosed with sporidesmin in combination with diosgenin developed liver lesions. These were typical of those induced by sporidesmin. One lamb dosed with sporidesmin in combination with 9 g of diosgenin developed a crystal-associated cholangitis typical of Panicurn intoxication and alveld. No sapogenins were detected in urine by gas chromatography-mass spectrometry. The results suggest that orally administered sarsasapogenin and diosgenin are either not hepatotoxic per se or are too poorly absorbed to elicit a toxic response. The results provide only weak evidence that sporidesmin may be involved in the aetiology of Panicurn intoxication. 相似文献
3.
Alveld is a hepatogenous photosensitization disease seen in lambs grazing Narthecium ossifragum pastures in Norway. Mycotoxins, possibly sporidesmin, have been suspected to cause the liver damage in alveld as in facial eczema. The histological changes in the liver of alveld cases and in lambs photosensitized after experimental sporidesmin intoxication were compared. The liver damage characterized by necrosis in single centrilobular hepatocytes, was of the same type in both conditions. Minor to moderate portal fibroplasia and bile duct proliferation were almost always present. Accumulated glycogen was seen in hepatocytes in the centrilobular areas. This was significantly correlated to the enzymatically measured glycogen content and there was good correlation between parenchymal damage and glycogen accumulation. The glucose-6-phosphatase and glycogen phosphorylase activities were normal. These findings indicate that parenchymal damage, rather than obstruction of the bile ducts, caused the retention of phylloerythrin both in alveld cases and in experimentally sporidesmin-intoxicated lambs. The accumulation of glycogen could not be explained.Abbreviations HE
haematoxylin and eoson
- PAS
periodic acid Schiff
- EDTA
ethylene diamine tetracetic acid 相似文献
4.
Zinc sulphate solution, administered concurrently with the mycotoxin sporidesmin, gave significant protection against the toxin. The protective effect was shown in maintained milk production and bodyweights, and in reduced liver damage as determined by serum enzyme (gamma-glutamyltransferase, ornithine carbamyltransferase) analysis and by subjective grading of the liver damage after slaughter. There was no overt facial eczema in either group but, in sporidesmin dosed cows not receiving zinc sulphate, there was a fall in milk yield and in bodyweight. Serum enzyme levels did not rise until more than a week after dosing at which time milk yields were showing partial recovery. Serum concentrations of the enzyme gamma-gluta-myltransferase (EC 23.2.2) were found to be correlated to the severity of the liver damage observed at post-mortem. 相似文献
5.
van Wuijckhuise L Snoep J Cremers G Duvivier A Groeneveld A Ottens W van der Sar S 《Tijdschrift voor diergeneeskunde》2006,131(23):858-861
Between mid September and the beginning of November 2005, the Animal Health Service (AHS) received thirteen reports offarms on which several animals showed severe symptoms of solar eczema. Blood chemistry showed very high levels of GOT/AST and GGT indicative of severe liver damage. Farm visits to eight farms showed that the animals--previous to the start of the symptoms--had been grazing 24 hours/day and received no additional feed. Ingestion of poisonous plants or medications was considered unlikely to have caused the liver damage, and liver fluke infections were present on only two farms. Microscopic examination of specimens of grass revealed the presence of spores of Pithomyces chartarum in samples taken from six of nine farms. This fungus produces the mycotoxin sporidesmin, which causes severe liver damage and pithomycotoxicosis (facial eczema). This article is the first to describe Pithomyces chartarum in cattle in mainland Europe. Further research on the distribution and re-occurrence of Pithomyces chartarum infection and sporidesmin survival in grass silage is recommended. 相似文献
6.
W.C. Barry M.R.C.V.S. 《New Zealand veterinary journal》2013,61(2):51-52
A field outbreak of facial eczema occurred during a vitamin B12 response trial in young growing sheep. Pasture cobalt levels were in the low range for sheep <0.08 mg/kg, 1.358 µmol/kg) and mean (of 3) liver vitamin B12 levels in the sheep were low (>100 nmol/kg) during the period in which facial eczema occurred. Mean serum vitamin B12 levels of the untreated group were low (>185 pmol/1) for the two months (January and February) preceding the period of facial eczema. However, levels showed an approximate 3.5 fold increase in both cobalt supplemented and unsupplemented groups with the onset of facial eczema in March. From February to March the mean serum vitamin B12 and glutamyl transferase (GGT) activity showed parallel increases with a positive correlation (r = 0.73) between log serum vitamin B12 and log serum GGT activity during the period January to July for both groups. This finding suggested that the increase in serum vitamin B12 was due to sporidesmin induced liver damage. The diagnostic implication is that, in areas where facial eczema is a problem, liver is the sample of choice for determining vitamin B12 status, because sporidesmin toxicity can elevate low serum vitamin B12 levels to diagnostically normal levels. 相似文献
7.
A field outbreak of facial eczema occurred during a vitamin B12 response trial in young growing sheep. Pasture cobalt levels were in the low range for sheep (<0.08 mg/kg, 1.358 micromol/kg) and mean (of 3) liver vitamin B12 levels in the sheep were low (<400 nmol/kg) during the period in which facial eczema occurred. Mean serum vitamin B12 levels of the untreated group were low (<485 pmol/l) for the two months (January and February) preceding the period of facial eczema. However, levels showed an approximate 3.5 fold increase in both cobalt supplemented and unsupplemented groups with the onset of facial eczema in March. From February to March the mean serum vitamin B12 and glutamyl transferase (GGT) activity showed parallel increases with a positive correlation (r = 0.73) between log serum vitamin B12 and log serum GGT activity during the period January to July for both groups. This finding suggested that the increase in serum vitamin B12 was due to sporidesmin induced liver damage. The diagnostic implication is that, in areas where facial eczema is a problem, liver is the sample of choice for determining vitamin B12 status. because sporidesmin toxicity can elevate low serum vitamin B12 levels to diagnostically normal levels. 相似文献
8.
Munday R Thompson AM Smith BL Towers NR O'Donnell K McDonald RM Stirnemann M 《New Zealand veterinary journal》2001,49(1):29-33
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. 相似文献
9.
B.L. Smith 《New Zealand veterinary journal》2013,61(6):176-181
Aim: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days. Methods: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded. Results: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease. Conclusions: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals.These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep. 相似文献
10.
Morris CA Towers NR Hohenboken WD Maqbool N Smith BL Phua SH 《New Zealand veterinary journal》2004,52(5):205-215
Facial eczema (FE) is a costly problem to New Zealand pastoral agriculture, and has a detrimental impact on animal wellbeing. Incidence and severity of the disease can be reduced by grazing management and zinc prophylaxis. An additional strategy is to breed animals that are genetically resistant to intoxication with sporidesmin, the causative mycotoxin. This review summarises research findings on the inheritance of resistance of animals to FE, including evidence of among- and within-breed genetic variation, direct and correlated responses to selection, and identification of genetic markers and candidate genes for FE resistance. 相似文献
11.
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, to female 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. When sporidesmin D was administered in two separate doses to sheep bred for either resistance or susceptibility to facial eczema, the variability of metabolic output between sheep within groups was much less after the second dose. The mean urinary metabolite excretion was greater for the susceptible than the resistant sheep but the difference was not significant. Potentiation (caused by pre-administration of small doses of sporidesmin A) resulted in a more severe reaction to the dosed sporidesmin A. Urinary output of metabolite was less in the potentiated than in the unpotentiated sheep. When resistant and susceptible sheep were dosed with sporidesmin A after potentiation there was no difference between them in their cumulative totals or excretion rates of immunoreactive metabolites. However, the volume of urine produced by the susceptible sheep was lower and less variable than the resistant sheep and consequently the concentration of their urinary metabolites was higher. Preliminary ELISA examination of HPLC-fractionated urine from a sheep dosed with sporidesmin A indicated the presence of several metabolites of sporidesmin. CONCLUSION: Sporidesmin A and metabolites are rapidly excreted in urine but not as rapidly as sporidesmin D and its metabolites. Only minor differences between sheep bred for resistance and susceptibility were seen. Potentiation caused a more severe reaction to sporidesmin A and less urinary excretion of the sporidesmin and its metabolites. CLINICAL RELEVANCE: This work is part of a programme with the aim of identifying FE-resistant animals without the need for sporidesmin dosing. 相似文献
12.
Smith BL 《New Zealand veterinary journal》2000,48(6):176-181
AIM: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days. METHODS: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded. RESULTS: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease. CONCLUSIONS: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals. These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep. 相似文献
13.
Hum S 《Australian veterinary journal》2005,83(11):678-679
A 2-year-old, captive, male Eastern Grey kangaroo (Macropus giganteus) died after progressive weight loss over a 4 week period. Biochemical analysis suggested hepatobiliary injury. At necropsy the liver was small, pale and firm. There were no abnormalities detected in other organs. Histopathological examination revealed a severe, diffuse, obliterative cholangiohepatopathy with advanced periportal fibrosis. This chronic hepatotoxicity was consistent with exposure to sporidesmin, the toxic metabolite in the spores of the fungus Pithomyces chartarum. Restricted grazing opportunities and heavy fungal pasture contamination may have precipitated sporidesmin toxicity in this animal. Sporidesmin toxicity has not previously been reported in this species. 相似文献
14.
The distribution of 5'-nucleotidase (5'-NT) activity in the tissues of the sheep differs from that of gamma glutamyl transferase (GGT). Nevertheless, both enzymes are released into the plasma of sheep which have been infected with Fasciola hepatica or in which the bile duct has been ligated. In a sheep dosed with sporidesmin, a fungal toxin which damages the biliary tract, there was an increase in GGT activity in the plasma and urine but no change in 5'-NT activity. Neither enzyme was released into the plasma or urine of sheep dosed with carbon tetrachloride. In sheep with renal tubular necrosis and hepatocellular necrosis caused by dosage with hexachlorobutadiene, both enzymes were released into the plasma, and GGT, but not 5'-NT activity was found in urine. In sheep with tubular necrosis of the kidney caused by the administration of mercuric chloride, GGT activity, but not 5'-NT, increased in the plasma and urine. 相似文献
15.
AIMS: To study the increase in phylloerythrin concentration in plasma and the disposition of phylloerythrin in skin and other tissues of sheep in which the hepatogenous photosensitisation,facial eczema, had been experimentally induced by dosing with the mycotoxin, sporidesmin. Spectroscopic differences between plasma and skin measurements of animals kept inside and outside after dosing were also studied in order to establish whether phylloerythrin undergoes photodegradation when exposed to sunlight. METHODS: Twenty-six Romney x Polled Dorset (25-30 kg)weaned female lambs were purchased from a commercial flock in the Waikato region, New Zealand. Twenty-two of these lambs were dosed with 0.25 mg sporidesmin/kg liveweight on each of two consecutive days (Days -1 and 0); the remaining four lambs served as controls. Both sporidesmin-dosed lambs and controls were randomly divided into two penned groups, one group housed inside in a darkened room and the others outside, exposed to natural sunlight. The lambs were fed green lucerne pellets and lucerne chaff ad libitum for 10 days prior to dosing and until Day 12 after the first dose; thereafter, all the lambs were fed fresh, cut grass (mainly ryegrass) ad libitum, until the end of the experimental period on Day 26. Plasma samples collected on Days -2, 7, 10, 12, 14, 17, 20 and 25were analysed for gamma glutamyltransferase (GGT) activity, bilirubin concentration, and the fluorescence spectrum of phylloerythrin. Spectrofluorometric analysis of phylloerythrin in skin was performed in vivo on the same days, using an external fiber-optic probe. RESULTS: Eight of 11 lambs (73%) kept outside after sporidesmin dosing became photosensitised during the experimental period. None of the sporidesmin-dosed animals kept inside showed clinical signs of photosensitisation. The GGT activity in plasma increased exponentially during the experimental period in all sporidesmin-dosed animals until it reached a plateau. All plasma obtained from sporidesmin-dosed sheep had spectral characteristics similar to those of phylloerythrin, namely a peak in the excitation spectrum at 422 nm and strong emission band at 650 (SE 1) and 709 (SE 1) nm. The fluorescence under excitation at 422 nm of phylloerythrin added to plasma from control lambs had identical peaks. Emission spectra obtained from plasma from healthy sheep without addition of phylloerythrin showed either no fluorescence or minor fluorescence at around 671 nm. Fluorescence in skin of sporidesmin-dosed animals had similar spectra to that in plasma. The appearance of the phylloerythrin-like spectra occurred 2-3 days later in the skin than in plasma, and phylloerythrin in sunlight-exposed skin did not suffer photodegradation during the course of the study. CONCLUSION: Plasma concentrations of phylloerythrin in healthy sheep were <0.1 micromol/l, and clinical signs of photosensitisation were not evident until concentrations exceeded 0.3 micromol/l. Plasma concentrations of phylloerythrin rose as high as 4.9 micromol/l in some animals. The concentration of phylloerythrin in skin began increasing 2-3 days later than that in blood. Hepatogenous photosensitisation can be diagnosed by analysis of plasma phylloerythrin concentrations using a spectroscopic method. 相似文献
16.
Groups of six goats were orally dosed with sporidesmin at rates of 0.3, 0.6, 1.2 and 2.4 mg of sporidesmin per kg body weight and their responses up to 6 weeks later compared with those of sheep dosed at the same time. Clinical facial eczema and pathological lesions similar to those found in sheep were found in all the goat breeds, but at higher dose rates of sporidesmin than those which caused equivalent lesions in sheep. Saanens were the most susceptible goat breed, requiring 2-4 times as much sporidesmin as sheep to achieve similar effects. G4 and feral goats required 4-8 times the sheep dose of sporidesmin to obtain similar responses. Gamma-glutamyltransferase reached its highest serum levels after 20 days while glutamate dehydrogenase and aspartate aminotransferase reached their highest levels between 10 and 20 days. Alkaline phosphatase did not rise consistently to high levels in affected goats. The elevation in aspartate aminotransferase levels tended to be early and transient; glutamate dehydrogenase early and prolonged; gamma-glutamyltransferase late and prolonged, and'alkaline phosphatase late and minor. There was considerable individual variation in the time at which elevations occurred and the levels which enzymes reached. Cholesterol and bilirubin levels were high if liver injury was severe. 相似文献
17.
An examination was made of the relationship in Romney sheep between selenium deficiency and (i) the state of the liver drug metabolising enzyme system, (ii) subclinical liver damage, (iii) susceptibility to facial eczema, and (iv) susceptibility to ryegrasss staggers. The microsomal electron transport detoxifying enzymes based on cytochrome P-450 were unaffected by Se deficiency, suggesting that these enzymes are uninduced on ryegrass/clover pastures. Selenium deficiency had no effect on sporidesmin-induced liver damage, which makes it unlikely that peroxidative events countered by Se-dependent glutathione peroxidase (E.C.1.11.10) have a major role in the mechanism of sporidesmin toxicity. Selenium deficiency did appear to suppress the development of photosensitisation. There was no major effect on ryegrass staggers and no deficiency-induced subclinical liver damage. 相似文献
18.
TW Jordan 《New Zealand veterinary journal》2020,68(4):203-213
ABSTRACTThe 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 wide biological reactivity. The ways in which the toxin causes hepatobiliary and other tissue damage have not been established. Hypotheses include direct interaction with cellular thiols including protein cysteine residues or production of reactive oxygen species resulting in oxidative stress. Comparison with the cellular effects of the structurally related compound gliotoxin suggests additional mechanisms including interaction with cell adhesion complexes and possible downstream consequences for regulated necrosis as a response to tissue injury. Revision of hypotheses of how sporidesmin affects cells has the potential to generate new strategies for control of facial eczema including through identification of proteins and genes that are associated with resistance to the disease. 相似文献
19.
N.R. Towers 《New Zealand veterinary journal》2013,61(6):142-145
The incidence of subclinical facial eczema in 10 Waikato dairy herds was investigated using the serum enzyme γ-glutamyltransferase (GGT) as an indicator of liver disease. Although only 127 (9.4%) of the 1357 milking cows and 4 (2.6%) of the 155 calves and yearlings bled were recognised to have had clinical facial eczema, 39% of the cows and 48% of the young stock had abnormal serum GGT concentrations, indicating recent liver damage. Determining serum GGT activity, or body-condition grade, in May or July had no value in predicting which animals would suffer metabolic diseases, or calving problems, in the following spring. Severe liver damage did not apparently affect subsequent reproductive performance. 相似文献
20.
Topal A Gül N Ilçöl Y Görgül OS 《Journal of veterinary medicine. A, Physiology, pathology, clinical medicine》2003,50(10):530-533
The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic function and hepatocellular damage were investigated in dogs, comparing the activity of hepatic enzymes and bilirubin concentration in serum. An experimental study was designed. Twenty-one clinically normal mongrel dogs were divided into three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n = 7) and sevoflurane (n = 7). The dogs were 1-4 years old, and weighed between 13.5 and 27 kg (18.4 +/- 3.9). Xylazine HCI (1-2 mg/kg) i.m. was used as pre-anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The trachea was intubated and anaesthesia maintained with halothane, isoflurane or sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively. Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration rate, 12-14/min) was started immediately after intubation and the anaesthesia lasted for 60 min. Venous blood samples were collected before pre-medication, 24 and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT) activities and bilirubin concentration were measured. Serum AST, ALT and GGT activities increased after anaesthesia in all groups. In the halothane group, serum AST and ALT activities significantly increased all the time after anaesthesia compared with baseline activities. But in the isoflurane group AST and ALT activities increased only between 2 and 7 days, and in the sevoflurane group 7 days after anaesthesia. GGT activity was increased in the halothane group between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after anaesthesia. All dogs recovered from anaesthesia without complications and none developed clinical signs of hepatic damage within 14 days. The results suggest that the use of halothane anaesthesia induces an elevation of serum activities of liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia on the liver in dogs is safer than halothane anaesthesia in dogs. 相似文献