Fusariotoxicosis from barley in British Columbia. I. Natural occurrence and diagnosis.
Clinical sickness was observed in domestic ducks, geese, horses and swine during October 1973. All species showed upper alimentary distress with mortalities occurring in the geese. Barley derived from a common source had been fed. Examination of the barley revealed invasion by Fusarium spp and detection of a high level of dermatitic fusariotoxins. (+info)
Fusariotoxicosis from barley in British Columbia. II. Analysis and toxicity of syspected barley.
Fusariotoxin T-2, a trichothecene, was tentatively identified in barley samples which caused field outbreaks of mycotoxicosis in British Columbia. Geese died when fed the contaminated barley experimentally but mice were little affected after long term feeding. The methods used in the laboratory for trichothecene extraction and identification of T-2 toxin are described. (+info)
Mycotoxin determinations on animal feedstuffs and tissues in Western Canada.
Results of examination of specimens of plant or animal origin for various mycotoxins are presented. Analyses for aflatoxins and ochratoxins were most frequently requested, usually on the basis of visible mouldiness. Aflatoxin B1 was found in one of 100 specimens at a level of 50 ppb in a sample of alfalfa brome hay. Ochratoxin A was detected in seven of 95 specimens comprising six samples of wheat at levels between 30 and 6000 ppb and one sample of hay at a level of 30 ppb. An overall detection rate of 4.2% involving significant levels of potent mycotoxins suggests that acute or chronic mycotoxicoses may occur in farm livestock or poultry more frequently than presently diagnosied. (+info)
Natural occurrence of the C series of fumonisins in moldy corn.
We analyzed 44 moldy corn samples for the B and C series of fumonisins by high-performance liquid chromatography. Of the 44 samples, 32 (73%) were contaminated with both the B and C series of fumonisins and 6 were contaminated with only the B series of fumonisins. The incidence of fumonisin C1 in moldy corn was 71%; the incidence was 11% for fumonisin C3 and 43% for fumonisin C4. Their mean levels ranged from 500 to 1,900 ng/g. This is the first report on the natural occurrence of the C series of fumonisins and fumonisin B4 in moldy corn. (+info)
The effect of cyclopiazonic acid on the development of pale, soft, and exudative pork from pigs of defined malignant hyperthermia genotype.
Malignant hyperthermia (MH) and the mycotoxin cyclopiazonic acid (CPA) are each associated with abnormal calcium homeostasis in skeletal muscle, a key underlying factor in the development of pale, soft, and exudative (PSE) pork. To determine whether the natural presence of CPA in livestock feed ingredients contributes to the varying incidence of PSE in the pork industry, various levels of CPA (.1 to 50 mg/kg of diet) were included in the diets of market weight hogs (n = 52) of defined malignant hyperthermia genotype (NN = normal, Nn = a MH carrier, and nn = MH-positive). Animals with two copies of the MH mutation (nn) displayed improved live animal performance compared with NN and Nn animals (increased feed intake, average daily gain, and feed efficiency) but yielded lower quality loin chops as indicated by lower 45-min pH (P<.01), higher Commission Internationale de l'Eclairage (CIE) L* color coordinate values (P<.05), and higher drip losses (P<.01). The effects of CPA varied. In the first feeding trial, conducted under normal outside temperatures (2 degrees C), CPA had no effect (P> .2) on either live animal performance or meat quality. During the second trial, conducted under extreme outside temperatures (-18 degrees C), CPA-dependent reductions (P<.05) in feed intake, average daily gain, and 45-min pH in nn hogs support the possibility of interactions between malignant hyperthermia and dietary CPA on skeletal muscle calcium homeostasis and the development of PSE pork. These results suggest that this interaction may require stressful environmental conditions or the ingestion of CPA doses much higher than occur under natural conditions. (+info)
Analysis and pharmacokinetics of cyclopiazonic acid in market weight pigs.
The pharmacokinetic behavior of cyclopiazonic acid (CPA) was determined in market weight pigs using a competitive indirect ELISA developed for the determination of the mycotoxin in various biological matrices. Sample preparation for corn and skeletal muscle was achieved with a single extraction and recoveries of 53+/-6% over the effective range of the standard curve. The detection limit of CPA was 1 ppb in plasma, which required no extraction, and 20 ppb in corn and skeletal muscle with average intra- and interassay CV of 11 and 23%, respectively. Levels of CPA contamination in corn grown and stored in Michigan were unremarkable compared with published toxicity thresholds; the highest level of CPA found in any sample was 47 ppb. In pigs given a 20-mg i.v. bolus, CPA distributed rapidly among three compartments, with an overall volume of distribution (49 L) nearly equivalent to total body water. Cyclopiazonic acid was eliminated with a half-life of 24 h. Estimates of these pharmacokinetic parameters were supported by the achievement of steady-state plasma CPA levels within 6 d in pigs consuming a diet containing 10 ppm CPA, and by measured concentrations of CPA in plasma (410+/-44 ng/mL) and skeletal muscle (469+/-86 ng/ g). From these and other data, we concluded that the threat of CPA toxicity to livestock from consumption of cereal grains or to humans from consumption of animal products is minimal. (+info)
Multiple mechanisms confer drug resistance to mitoxantrone in the human 8226 myeloma cell line.
Selection for in vitro drug resistance can result in a complex phenotype with more than one mechanism of resistance emerging concurrently or sequentially. We examined emerging mechanisms of drug resistance during selection with mitoxantrone in the human myeloma cell line 8226. A novel transport mechanism appeared early in the selection process that was associated with a 10-fold resistance to mitoxantrone in the 8226/MR4 cell line. The reduction in intracellular drug concentration was ATP-dependent and ouabain-insensitive. The 8226/MR4 cell line was 34-fold cross-resistant to the fluorescent aza-anthrapyrazole BBR 3390. The resistance to BBR 3390 coincided with a 50% reduction in intracellular drug concentration. Confocal microscopy using BBR 3390 revealed a 64% decrease in the nuclear:cytoplasmic ratio in the drug-resistant cell line. The reduction in intracellular drug concentration of both mitoxantrone and BBR 3390 was reversed by a novel chemosensitizing agent, fumitremorgin C. In contrast, fumitremorgin C had no effect on resistance to mitoxantrone or BBR 3390 in the P-glycoprotein-positive 8226/DOX6 cell line. Increasing the degree of resistance to mitoxantrone in the 8226 cell line from 10 to 37 times (8226/MR20) did not further reduce the intracellular drug concentration. However, the 8226/MR20 cell line exhibited 88 and 70% reductions in topoisomerase II beta and alpha expression, respectively, compared with the parental drug sensitive cell line. This decrease in topoisomerase expression and activity was not observed in the low-level drug-resistant, 8226/MR4 cell line. These data demonstrate that low-level mitoxantrone resistance is due to the presence of a novel, energy-dependent drug efflux pump similar to P-glycoprotein and multidrug resistance-associated protein. Reversal of resistance by blocking drug efflux with fumitremorgin C should allow for functional analysis of this novel transporter in cancer cell lines or clinical tumor samples. Increased resistance to mitoxantrone may result from reduced intracellular drug accumulation, altered nuclear/cytoplasmic drug distribution, and alterations in topoisomerase II activity. (+info)
Serum levels of ochratoxin A in healthy adults in Tuscany: correlation with individual characteristics and between repeat measurements.
Ochratoxin A (OTA), a mycotoxin widely contaminating staple foods and beverages, has been classified as a "possible human carcinogen (Group 2B)" by the IARC. Serum levels of OTA were measured in a group of 138 healthy adults (age, 35-65 years) living in the area surrounding Florence (Tuscany, central Italy) and detected in all but four samples (97%). After the exclusion of one subject with a peak value of 57.2 ng/ml, OTA levels ranged between 0.12 and 2.84 ng/ml, with mean and median values of 0.56 and 0.48 ng/ml, respectively. OTA levels were significantly higher in men than in women (0.64 versus 0.50) and correlated positively with height. A strong association was found with the season in which blood samples were obtained, with summer values higher than autumn values. On the other hand, OTA levels tended to be negatively associated with blood pressure, either systolic or diastolic; no association was evident with age, weight, body mass index, and smoking history. The associations with height and season persisted in a multivariate regression analysis. A subgroup of subjects provided a repeat blood sample approximately 1 year later. The Spearman correlation coefficient between 68 pairs of original and repeat measurements was practically null (r = 0.05). Only two subjects (2.9%) had OTA levels of >1 ng/ml on both occasions. These results suggest that OTA contamination is widespread in foods consumed by this population, in agreement with previous reports from Italy and other countries. A strong seasonal variation, which possibly differs from year to year, was observed. OTA serum levels are a short-term biomarker with a high within-subject variability; therefore they have limited use at the individual level but can be used to characterize populations or subgroups of subjects. Additional analyses are needed to explore the dietary determinants of OTA levels in this population. (+info)