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Fusaric acid is produced by several species of Fusarium, which commonly infect corn and other agricultural commodities. Since this mycotoxin may augment the effects of other Fusarium toxins, a gas chromatography/mass spectrometry method of analysis in feeds was developed. Fusaric acid was analyzed as the trimethylsilyl-ester from F. moniliforme-cultures, -contaminated corn screenings, and feeds toxic to livestock. The mycotoxin was found in all samples and ranged from 0.43 to 12.39 micrograms/g sample. Also, fusaric acid was tested for its neurochemical effects in the brain and pineal gland of rats. Animals were dosed intraperitoneally (100 mg/kg body weight) 30 min prior to the onset of the dark phase (lights out) and the effects were studied at 1.5, 3.5, and 5.5 h after treatment. Brain serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), tyrosine (TYRO), and dopamine (DA) were increased (P < 0.05) by fusaric acid, and norepinephrine (NEpi) was decreased (P < 0.05). Analogously, DA in the pineal gland increased and NEpi decreased (P < 0.05). Pineal N-acetylserotonin (NAc5HT) was increased (P < 0.05), whereas pineal 5HT and its two major metabolites 5HIAA and 5-hydroxytryptophol (5HTOL) decreased (P < 0.05). Elevated brain TYRO and brain and pineal DA, with decreased NEpi, may be consistent with fusaric acid's partial inhibitory effect on tyrosine-hydroxylase and its inhibitory effect on dopamine-beta-hydroxylase, respectively. Elevated pineal Nac5HT is consistent with decreased pineal 5HT and the increased pineal DA, and support the dopaminergic stimulatory activity of the enzyme responsible for the conversion of 5HT to NAc5HT. This is the first report of fusaric acid's in vivo effect on pineal DA, NEpi, 5HT, and NAc5HT in rats, and a relation for the effects on TYRO, 5HT, and 5HIAA in brain tissue. The results indicate fusaric acid alters brain and pineal neurotransmitters and may contribute to the toxic effects of Fusarium-contaminated feeds.

Analysis of melatonin (MEL) in pineal cell cultures by enzyme linked immunosorbent assay showed its concentration was increased by fusaric acid (FA), a mycotoxin produced by Fusarium species and associated with toxic duck and ostrich feeds. Subsequent cell culture studies demonstrated the precursors of MEL, 5-hydroxytryptophan (5HTP) and serotonin (5HT), were also affected by FA as well as other Fusarium mycotoxins. Herein we describe a technique for the analysis of 5HTP and 5HT in pineal cell cultures using HPLC with electrochemical detection (EC), and report on the effects of FA alone and in combination with fumonisin B1 (FB1) and deoxynivalenol (DON) on the levels of these MEL precursors.

In 1995 airborne gamma-ray spectrometric data were acquired over the Endako porphyry molybdenum district in central British Columbia. Here we analyze these data together with surficial and lithogeochemical data to assess their utility as an aid to geological mapping and mineral exploration. Our results show that individual surficial units (e.g. till, glaciolacustrine, alluvium, etc.) cannot be distinguished in airborne data or geochemical analyses of surficial deposits. We observe small differences in mean radioelement concentrations between mapped bedrock units, even in areas of thick overburden; however, as all such differences are statistically insignificant, individual bedrock units cannot be uniquely identified by their radioelement response alone. We conclude that airborne spectrometry has limited mapping application where variations in bedrock compositions are subtle. Unlike other porphyry molybdenum occurrences in Canada, those in our study area are characterized by modest enrichments in both K and eTh relative to the host rock and significant eTh/K depletions are not observed. 1 Contribution to the Nechako NATMAP Project 1 Resume : En 1995, un leve aerien par spectrometrie a rayons gamma a ete realise dans le district du gisement porphyrique de molybdene d’Endako, dans la partie centrale de la Colombie-Britannique. L’analyse des donnees recueillies et des donnees sur les depots superficiels et sur la lithogeochimie visait a etablir leur valeur pour la cartographie geologique et l’exploration minerale. Selon les resultats obtenus, on ne peut pas distinguer les unites superficielles individuelles (p. ex. till, sediments glaciolacustres, alluvions, etc.) en utilisant les donnees aeriennes ou les analyses geochimiques des depots superficiels. Nous avons note de petites differences dans les concentrations moyennes des radio-elements entre les unites cartographiees du substratum rocheux, meme si la couverture de depots meubles est epaisse. Mais, comme ces differences ne sont pas statistiquement significatives, on ne peut pas faire uniquement appel aux radio-elements pour identifier les unites particulieres du substratum rocheux. En conclusion, la spectrometrie aerienne a des applications limitees en cartographie si la composition du substratum rocheux ne varie que faiblement. Contrairement aux autres gisements porphyriques de molybdene qui existent au Canada, ceux de la presente analyse sont moderement enrichis en K et eTh par rapport a la roche encaissante. Aucun appauvrissement significatif de eTh/K n’a ete observe.

Most manufacturing firms are under considerable pressure to increase their flexibility and responsiveness within the market. Key business processes concerned with responsiveness include information systems for demand management and manufacturing control. Overall, information systems account for almost a quarter of all IT investment within major manufacturing companies and much of this is currently being spent with ERP vendors who include BAAN, Oracle, SAP and MK Manufacturing (Vortman, 1998).

Analysis of melatonin (MEL) in pineal cell cultures by enzyme linked immunosorbent assay showed its concentration was increased by fusaric acid (FA), a mycotoxin produced by Fusarium species and associated with toxic duck and ostrich feeds. Subsequent cell culture studies demonstrated the precursors of MEL, 5-hydroxytryptophan (5HTP) and serotonin (5HT), were also affected by FA as well as other Fusarium mycotoxins. Herein we describe a technique for the analysis of 5HTP and 5HT in pineal cell cultures using HPLC with electrochemical detection (EC), and report on the effects of FA alone and in combination with fumonisin B1 (FB1) and deoxynivalenol (DON) on the levels of these MEL precursors.

Fusaric acid (FA) is produced by several Fusarium species that commonly infect cereal grains and other agricultural commodities. FA in the feed of nursing dams is lactationally transferred to the suckling offspring and alters serotonin (5-hydroxytryptamine, 5HT) in the pineal gland of the neonate rat. 5HT is involved in melatonin (MEL) production by the pineal gland. MEL is a hormone important in reproduction and seasonality in animals. Therefore, the effects of FA on MEL in the serum and pineal gland of male and female 21-d-old weanling rats from dams on an FA diet were studied. MEL was measured by enzyme-linked immunosorbent assay (ELISA), which was standardized for directly measuring MEL in rat serum and pineal homogenates. At 200 ppm in the diet of nursing dams, FA increased serum MEL in both sexes. Results obtained from ELISA were supported by high-performance liquid chromatography (HPLC) analysis with fluorescence detection. MEL analysis of the pineal gland homogenates by ELISA and HPLC supported observations in the serum. Analogously, in pineal cell monolayer cultures, FA at 1 microM and 100 microM concentrations increased MEL in a dose-dependent manner as compared to the control cells. This is the first report that FA increases MEL in vivo and in vitro and suggests that FA contamination of diets may affect mechanisms involving MEL synthesis.

Fusaric acid is a mycotoxin with low to moderate toxicity, which is of concern since it might be synergistic with other cooccurring mycotoxins. Fusaric acid is widespread on corn and corn-based food and feeds and is frequently found in grain, where Fusarium spp. are also isolated. We surveyed 78 strains of Fusarium moniliforme, F. crookwellense, F. subglutinans, F. sambucinum, F. napiforme, F. heterosporum, F. oxysporum, F. solani, and F. proliferatum for their ability to produce fusaric acid. Strains in Fusarium section Liseola also were assigned to mating population of the Gibberella fujikuroi species complex. The fungi could be divided into three classes, low (< 100 micrograms/g), moderate (100 to 500 micrograms/g), and high (> 500 micrograms/g), based on the amounts of this mycotoxin produced in culture on autoclaved corn. Strains of mating populations C from rice consistently produced moderate to high concentrations of fusaric acid. Two isolates, one each from mating populations C and D, produced fusaric acid in excess of 1,000 micrograms/g of corn. No isolates of any of the Fusarium species examined were negative for the production of fusaric acid on autoclaved corn.

Fusaric acid is produced by several species of Fusarium and is found in corn, corn-based foods and feeds, wheat, barley, and other cereal grains. Given parenterally to rats, the mycotoxin affects neurochemical parameters in the pineal gland associated with growth and maturation. Since little information exists concerning the dietary effects of fusaric acid, the mycotoxin was mixed with feed at 10, 75, and 200 ppm and fed ad libitum to pregnant rats (F0 dams) from d 11-12 of gestation, through parturition and weaning (F1 generation). On d 4 postpartum, F1 pups were culled to 9-10 pups/litter; the stomach colostrum was collected from the culls and analyzed for fusaric acid. The mycotoxin in the colostrum (ng fusaric acid/100 mg colostrum) was directly related to the amount consumed by the nursing dams (i.e., 200 ppm pups, 3547 ng; 75 ppm pups, 1449 ng; 10 ppm pups, 80 ng; controls pups, 18 ng). All other animals survived, and appeared normal, healthy, and in good pelage. F0 dam feed consumption and dam and pup weights were not statistically different, but there was an inverse relation between pup average weight gain and amount of fusaric acid in the diets (i.e., weight gains: control pup10 ppm pup75 ppm pups200 ppm pups). At weaning, the F1 pups were randomly assigned to two groups per treatment: one group (F1A) for reproduction and fusaric acid effects on the F2 generation, and another group (F1B) for neurochemical comparisons. The F1A rats were maintained on their respective diets to age 13-14 wk; animals were bred (i.e., control males x control females, 10 ppm x 10 ppm, etc.) and the F1A dams and F2 pups were monitored as already described. Weight gains and fusaric acid in stomach colostrum from the F2-culls were analogous to the F1 generation. On d 5-6 and 7-8 postpartum, using litter weight gains as an indication of milk production in the F1A dams (controls vs. 200 ppm), the controls gained 32.5% (p.01) and 13.3% (p.02), respectively, more than 200 ppm F2 pups. At weaning, no differences were observed in neurochemicals in the pineal gland for the F1 generation. However, in the F2 200 ppm male and female weanlings, fusaric acid decreased pineal serotonin (males, por = .001; females, por = .15) and tyrosine (males, por = .04; females, por = .07). The results indicate fusaric acid in diets ator = 0.3 ppm (i.e., background control diet) lactationally passes from nursing dams to the neonate; in weanlings, at 200 ppm, fusaric acid decreases pineal serotonin and tyrosine. The data also suggest limited neonate weight gains may be related to either decreased milk production in dams or mycotoxin effects on the neonate. This is the first report of fusaric acid's lactational passage from the feed of nursing dams to neonates and the oral suppression of pineal serotonin and tyrosine in offspring.

Toxic interactions of fusaric acid and fumonisin B1, two mycotoxins produced by Fusarium moniliforme, were studied in the chicken embryo. The yolk sacs of fertile White Leghorn eggs were injected before incubation with separate and combined solutions of either fusaric acid and or fumonisin B1. The toxins were administered in either a sterile 10 mM buffered phosphate solution, pH 6.90, which produced a final pH of 6.6 +/- 0.2, or sterile distilled water. Toxicity was based on absence of egg pip at the end of the 21-day incubation period. Toxins administered in the phosphate buffer solution were more toxic than those administered in distilled water. When both toxins were combined in equal concentrations and injected into eggs, increased toxicity resulted. Fusaric acid was shown to be a mild toxin to the eggs and when a relatively nontoxic concentration of it was combined with graded doses of fumonisin B1, a synergistic toxic response was obtained. Fusaric acid is only moderately toxic to the chicken egg, however its co-occurrence with other fusaria toxins found on corn and other cereals might present possible antagonisms or synergisms. The results of this egg model suggest that fusaric acid might play a role in enhanced and unpredicted toxicity in mammalian systems if it is consumed with other mycotoxins.

Plasma and pineal melatonin (MEL) and selected pineal neurochemicals (5-hydroxytryptophan, serotonin, N-acetylserotonin, dopamine, norepinephrine) associated with MEL synthesis were determined in steers grazing Acremonium coenophialum (endophyte)-infected 'Kentucky-31' tall fescue paddocks. Paddock treatments included low (LE, 33%) or high (HE, 74%) endophyte at either low (134 kg.ha-1 x yr-1, LN) or high (335 kg.ha-1 x yr-1, HN) nitrogen fertilization. Twelve pairs of yearling Angus steers were randomly assigned to three replications of the paddock treatments (LEHN, HEHN, LELN, and HELN). One steer in each of the 12 paddocks received per os either a dopamine antagonist, metoclopramide (MC; 15 mg/kg), or sucrose (S; 15 mg/kg) three times weekly for 10 wk. Blood was collected via jugular cannulas during the day and night for plasma MEL analysis and pineal glands were collected at termination. Day and night plasma MEL in the S/HEHN steers was reduced by 31.7 and 35.4% (P.05), respectively, compared with that in S/LEHN steers. Mean night plasma MEL in the S/HELN steers was reduced by 26.7% (P.05) compared with that in S/LELN steers. Metoclopramide reduced mean day and night plasma MEL by 22.9 and 38.3% (P.05), respectively, in the LEHN steers and increased night MEL in the HELN animals by 35.1% (P.05). During the day and night, there was a MC x pasture treatment interaction (P.05). No differences were observed in either pineal MEL or the pineal neurochemicals. Acremonium coenophialum-infected fescue reduced plasma concentrations of MEL in steers, whereas treatment with MC altered plasma MEL biphasically.(ABSTRACT TRUNCATED AT 250 WORDS)

Fumonisin B1, a toxin produced by Fusarium moniliforme, has been associated with a neurotoxic syndrome in horses known as equine leukoencephlomalacia. Previous investigations showed that F. moniliforme cultured on corn and incorporated into rat chow increased brain 5-hydroxyindoleacetic acid (5HIAA) and 5HIAA: serotonin (5HT) ratios in these animals. Therefore, this study was undertaken to determine whether fumonisin B1 would produce related neurochemical effects in the brain and pineal gland of male and female rats. Rats were fed fumonisin B1 at 15, 50, and 150 ppm for 4 weeks. No differences occurred in brain concentrations of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, 5HT, 5HIAA, and the 5HIAA to 5HT ratios in either male or female rats, nor where there differences between the sexes. When compared across sexes, the norepinephrine to dopamine ratios were decreased (P < 0.05) in the 150-ppm-treated animals. This may suggest a fumonisin B1-induced imbalance in brain norepinephrine and/or dopamine. No differences were observed in pineal norepinephrine, 5HT, 5HIAA, and the 5HIAA to 5HT ratios. Since fumonisin B1 failed to duplicate the effects of the F. moniliforme-induced imbalances in 5HT and 5HIAA metabolism in the brains of rats, other mycotoxins from F. moniliforme may be responsible for these effects.

Different signs of ergotism in livestock associated with animals consuming feed grains and pasture grasses infected by Clavicipitaceae (e.g. Balansia spp. and Acremonium spp.) have been considered. Endophyte-infected tall fescue causes the damage to livestock, and its toxicity and ryegrass in livestock are associated with ergopeptide alkaloid ergovaline and indole-isoprenoid lolitrems produced by A. coenophialum and A. lolii. The role of another compound attendant to endophyte-infected fescue such as peramine and loline alkaloid is discussed. Concentration of alkaloids depends upon the season and the period of growing plant-host. The advantages and the problems of endophyte-grass mutualistic symbiosis in pasture conditions are considered. The perspective of genetic manipulation of grass and fungus to produce endophyte-infected grasses with stress and insect deterences without affecting ruminant health.

Ethical values and principles are singular and immutable, but this is not true of their interpretation and application. In Mexico, even though these values and principles are respected in medical practice, the teaching of bioethics is non-existent and in most of the schools for health professionals the subject is not included in the curriculum. Nevertheless, Mexican society has made notable progress in the legislation and regulation of ethical aspects of such activities as research on human subjects, fertility regulation, the right to death with dignity, organ transplants, and AIDS.

In Mexico, as in many other countries, there are numerous situations involving bioethics that are not necessarily covered by officially sanctioned policies or guidelines. In such cases, it is reasonable to describe commonly accepted rules, opinions, and practices in a general way so as to illustrate how bioethical questions are being managed. This article describes certain goals and practices relating to education in bioethics in Mexico. It then outlines Mexican laws and procedures governing research on human subjects, cites certain official rules and activities relating to regulation of human reproduction, quotes literature dealing with intervention in human procreation, discusses artificial prolongation of life, describes laws and practices governing organ transplants, considers ethical issues relating to such transplants, reviews the AIDS situation, and describes how the need for confidentiality is dealt with in managing AIDS cases and related data. In this manner it indicates how bioethical questions in these various areas are being handled and points out certain priority areas needing work.

Dopamine (DA), serotonin (5HT) and selected precursors and metabolites were measured in the anterior pituitary gland, hypothalamus and pineal gland, along with serum prolactin (PRL) and average daily gains (ADG), in steers (n = 6/group) grazing endophyte (Acremonium coenophialum)-infected and noninfected fescue (Festuca arundinacea Schreb). Paddocks (two/treatment) were designated 100F and 0F (100 and 0% infection, respectively). After 6 wk, three animals from one of the 100F paddocks were exchanged with three animals from one of the 0F paddocks, yielding 0F, 100F/0F, 0F/100F and 100F groups (n = 3). Compared to 0F steers, 100F steers had reduced serum PRL (9.23 vs 32.55 ng/ml, P less than or equal to .0001) and trial ADG (-.07 vs .28 kg, P less than or equal to .0002) but increased pituitary dihydroxyphenylacetic acid (DOPAC, a major metabolite of DA; 108 vs 59 ng/g, P less than or equal to .02) and 5-hydroxyindoleacetic acid (5HIAA, a major metabolite of 5HT; 265 vs 148 ng/g, P less than or equal to .04). Pituitary 5HIAA was greater in the steers rotated from the 0F to 100F paddocks than in steers maintained on the 0F paddocks (296 vs 148 ng/g, P less than or equal to .04). In addition pineal 5-hydroxytryptophan (5HTP, a precursor of 5HT) was increased (502 vs 280 ng/ml; P less than .08), whereas 5-methoxyindoleacetic acid (MIAA, a major metabolite of 5HIAA) and the 5HT/5HTP ratio were reduced (P less than .07) in 100F vs 0F steers. No differences among the treatment groups were observed in hypothalamic neurotransmitter and metabolite concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

The ability of quipazine and metoclopramide to protect rats from CB-154-induced suppression of serum prolactin concentrations was studied. These drugs affect whole brain concentrations of dopamine and serotonin, and their major metabolites dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid. Serum prolactin concentrations have been correlated with the concentrations of the neurotransmitters and their respective metabolites. Differences in the metabolite/precursor ratios have been used to compare turnover rates of the neurotransmitters dopamine and serotonin. Increased turnover of dopamine and decreased turnover of serotonin correlate with elevated prolactin concentrations for quipazine and metoclopramide administered together. The combination of quipazine and metoclopramide protects rats against CB-154-induced prolactin suppression better than either of the drugs given alone. This study suggests that a quipazine-metoclopramide regimen may have therapeutic potential for combating ergotlike fescue and other similar toxicities observed in cattle grazing on endophyte-infected pasture grasses.

Four species of Balansia (clavicipitaceous systemic grass pathogens) isolated from pastures where cattle showed signs of ergot toxicity were grown in culture. Balansia epichloe, one isolate of B. claviceps, B. henningsiana and two isolates of B. strangulans produced conidia in submerged culture during the first stage of a two-stage fermentation procedure. When transferred to a glucose/sorbitol/inorganic salts medium during the second stage, these four species produced ergot alkaloids in stationary cultures. The transfer of fungi cultured in the first medium to the second medium was necessary for alkaloid biosynthesis. One isolate of B. claviceps did not produce alkaloids. Balansia epichloe produced chanoclavine (I), agroclavine, penniclavine, elymoclavine, ergonovine and ergonovinine. Balansia claviceps produced chanoclavine (I), ergonovine and ergonovinine. This is the first report of isolating ergonovine and ergonovinine, two lysergic acid derivatives, from fungi outside the genus Claviceps. Only chanoclavine (I) was identified from extracts of B. strangulans and B. henningsiana. Chanoclavine (I) and ergonovine were identified from smut grass (Sporobolus poiretii) parasitized by B. epichloe, indicating that this endophyte produces alkaloids both in vivo and in vitro.

Crystals of the title compound are monoclinic, space group C2/c, with dimensions a= 26·04, b= 9·24, c= 9·45 A, β= 94·25°. The structure was solved by Fourier methods and the molecular parameters refined by full-matrix least-squares calculations to R 0·102 for 1681 independent reflexions. The copper atom lies on the crystallographic centre of symmetry with Cu–O(acetate) 1·976 and Cu–N 2·052 A. Distorted octahedral co-ordination around the copper atom is completed by bridging water molecules, Cu–O(water) 2·595 A, which are shared by adjacent octahedra. The remaining water molecules, which are not co-ordinated to the copper atom, form a hydrogen-bonded chain. The single-crystal e.s.r. spectrum and powder magnetic susceptibilities over the temperature range 80–300 K are discussed in terms of the structure. The magnetic susceptibilities of the aniline and p-toluidine adducts of Cu(BuO2)2 and Cu(PrO2)2 are also reported and discussed.

The use of bacterial bioluminescence as a toxicological assay for mycotoxins was tested with rubratoxin B, zearalenone, penicillic acid, citrinin, ochratoxin A, PR-toxin, aflatoxin B1, and patulin. The concentrations of mycotoxins causing 50% light reduction (EC50) in Photobacterium phosphoreum were determined immediately and at 5 h after reconstitution of the bacteria from a freeze-dried state. Generally, less toxins were required to obtain an EC50 at 5 h. The effects of the above mycotoxins on bioluminescence were determined after 5, 10, 15, and 20 min of incubation with the bacterial suspensions. The concentration of rubratoxin B necessary to elicit an EC50 increased with time, whereas the concentration of citrinin, penicillic acid, patulin, and PR-toxin necessary decreased with time. There was very little change in the concentration of zearalenone, aflatoxin B1, and ochratoxin A required to elicit an EC50 with time. The bacterial bioluminescence assay was most sensitive to patulin and least sensitive to rubratoxin B.

Investigations into diseases in cattle grazing on grass pastures infected with clavicipitaceous fungi have resulted in the isolation and characterization of erythro and threo 1-(3-indolyl) propane-1,2,3-triol from cultures of Balansia epichloë (Weese). Gas chromatography-mass spectroscopy analyses of synthetic and natural epimers as their trimethylsilyl derivatives is described. Toxicity studies with fertile chicken eggs demonstrated that the threo epimer was the more active compound. The ratio of erythro to threo was calculated at 3:2 in the natural isolate.

The single-crystal polarised electronic spectra, e.s.r., and magnetic anisotropy of tetra-(6-aminohexanoic acid)copper(II) diperchlorate are reported. These properties are interpreted by use of a point-charge crystal-field model and are seen to be consistent with the relative orbital energies, dxy > dx2–y2 > dz2 > dxz yz. The crystal-field parameters obtained are shown to agree closely with those for CaCu(AcO)4,6H2O when allowance is made for the different Cu–O distances involved.