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1.
Toxins (Basel) ; 13(10)2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34678976

RESUMO

Central Kentucky horse pastures contain significant populations of tall fescue (Schedonorus arundinacea (Schreb.) Dumort) infected with an endophyte (Epichloë coenophialum (Morgan-Jones and Gams) Bacon and Schardl) known to produce several ergot alkaloids, with ergovaline in the highest concentration. While most classes of horses are not adversely affected by average levels of ergovaline in pastures, late term pregnant mares have a low tolerance to ergovaline and the related ergot alkaloids. Endophyte-infected tall fescue has been known to cause prolonged gestation, thickened placenta, dystocia, agalactia, and foal and mare mortality. The University of Kentucky Horse Pasture Evaluation Program utilizes ergovaline and endophyte testing, as well as pasture species composition, to calculate ergovaline in the total diet in broodmare pastures. This data is used to develop detailed management recommendations for individual pastures. Application of these recommendations has led to reduced tall fescue toxicity symptoms on these farms, as well as improved pasture management and improved forage quality and quantity.


Assuntos
Ergotaminas/análise , Doenças dos Cavalos/prevenção & controle , Micoses/veterinária , Poaceae/microbiologia , Ração Animal/análise , Criação de Animais Domésticos/métodos , Animais , Endófitos , Epichloe/isolamento & purificação , Feminino , Cavalos , Kentucky , Micoses/prevenção & controle , Gravidez , Complicações na Gravidez/prevenção & controle , Complicações na Gravidez/veterinária
2.
Toxins (Basel) ; 13(7)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34357964

RESUMO

In the past centuries consumption of bread made of ergot-infected flour resulted in mass poisonings and miscarriages. The reason was the sclerotia of Claviceps purpurea (Fr.) Tul.-a source of noxious ergot alkaloids (ergotamine and ergovaline). The authors have searched the 19th century medical literature in order to find information on the following topics: dosage forms of drugs based on ergot and their application in official gynecology and obstetrics. The authors also briefly address the relevant data from the previous periods as well as the 20th century research on ergot. The research resulted in a conclusion that applications of ergot in gynecology and obstetrics in the 19th century were limited to controlling excessive uterine bleeding and irregular spasms, treatment of fibrous tumors of the uterus, and prevention of miscarriage, abortion, and amenorrhoea. The most common dosage forms mentioned in the works included in our review were the following: tinctures, water extracts (Wernich's and Squibb's watery extract of ergot), pills, and powders. The information documented in this paper will be helpful for further research and helpful in broadening the understanding of the historical application of the described controversial crude drugs. Ergot alkaloids were widely used in obstetrics, but in modern times they are not used in developed countries anymore. They may, however, play a significant role in developing countries where, in some cases, they can be used as an anti-hemorrhage agent during labor.


Assuntos
Alcaloides de Claviceps/uso terapêutico , Claviceps , Ergotamina , Ergotaminas , Ginecologia , Dietilamida do Ácido Lisérgico/análogos & derivados , Obstetrícia
3.
Molecules ; 26(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207051

RESUMO

An ultra-high performance liquid chromatography coupled to tandem mass spectrometry method is proposed for the determination of the major ergot alkaloids (ergometrine, ergosine, ergotamine, ergocornine, ergokryptine, ergocristine) and their epimers (ergometrinine, ergosinine, ergotaminine, ergocorninine, ergokryptinine, and ergocristinine) in oat-based foods and food supplements. A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure was applied as sample treatment, reducing the consumption of organic solvent and increasing sensitivity. This method involved an extraction with acetonitrile and ammonium carbonate (85:15, v/v) and a clean-up step based on dispersive solid-phase extraction, employing a mixture of C18/Z-Sep+ as sorbents. Procedural calibration curves were established and limits of quantification were below 3.2 µg/kg for the studied compounds. Repeatability and intermediate precision (expressed as RSD%) were lower than 6.3% and 15%, respectively, with recoveries ranging between 89.7% and 109%. The method was applied to oat-based products (bran, flakes, flour, grass, hydroalcoholic extracts, juices, and tablets), finding a positive sample of oat bran contaminated with ergometrine, ergosine, ergometrinine, and ergosinine (total content of 10.7 µg/kg).


Assuntos
Avena/química , Alcaloides de Claviceps/química , Alimento Funcional/análise , Carbonatos/química , Cromatografia Líquida de Alta Pressão/métodos , Ergolinas/química , Ergonovina/química , Ergotaminas/química , Contaminação de Alimentos/análise , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos
4.
Toxins (Basel) ; 13(5)2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925104

RESUMO

The natural occurrence of six major ergot alkaloids, ergometrine, ergosine, ergotamine, ergocornine, ergokryptine and ergocristine, as well as their corresponding epimers, were investigated in 60 cereal samples (barley and wheat) from Algeria. Ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and a QuEChERS extraction method were used for sample analysis. The results revealed that 12 out of 60 samples (20%) were contaminated with ergot alkaloids. Wheat was the most contaminated matrix, with an incidence of 26.7% (8 out of 30 samples). The concentration of total ergot alkaloids ranged from 17.8 to 53.9 µg/kg for barley and from 3.66 to 76.0 µg/kg for wheat samples. Ergosine, ergokryptine and ergocristine showed the highest incidences in wheat, while ergometrine was the most common ergot in barley.


Assuntos
Alcaloides de Claviceps/análise , Hordeum/química , Triticum/química , Argélia , Cromatografia Líquida de Alta Pressão , Ergolinas/análise , Ergonovina/análise , Ergotamina/análise , Ergotaminas/análise , Microbiologia de Alimentos , Limite de Detecção , Espectrometria de Massas em Tandem
5.
Artigo em Inglês | MEDLINE | ID: mdl-33784227

RESUMO

Cereals and feed contaminated with ergot alkaloids (EAs) have been of concern for several decades. Nowadays, analysis of EAs is focused on ergometrine, ergotamine, ergosine, ergocristine, ergocryptine (a mixture of α- and ß-isomers) and ergocornine and their related -inine epimers as listed in the European Commission Recommendation 2012/154/EU. Liquid chromatography with fluorescence detection has been used for quantification of EAs for decades whilst LC-MS has become the work-horse for quantification of EAs in the last decade. However, in LC-MS analysis matrix effects of different magnitudes exist for each EA epimer, especially ergometrine/ergometrinine, even after different clean-up procedures. This leads to an underestimation or overestimation of EAs levels. Moreover, isotopic labelled standards for EAs are still not available in the market. This review aims to provide background information on different analytical methods, discuss their advantages and disadvantages and possible advancement. Moreover, the method performance requirements to support forthcoming regulations are also discussed.


Assuntos
Grão Comestível/química , Alcaloides de Claviceps/análise , Contaminação de Alimentos/análise , Toxinas Biológicas/análise , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Ergolinas/análise , Ergotaminas/análise , Humanos , Lipídeos/química , Espectrometria de Fluorescência , Espectrometria de Massas em Tandem
6.
Toxins (Basel) ; 13(2)2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498584

RESUMO

Epichloë endophytes are filamentous fungi (family Clavicipitaceae) that live in symbiotic associations with grasses in the sub family Poöideae. In New Zealand, E. festucae var. lolii confers significant resistance to perennial ryegrass (Lolium perenne) against insect and animal herbivory and is an essential component of pastoral agriculture, where ryegrass is a major forage species. The fungus produces in planta a range of bioactive secondary metabolites, including ergovaline, which has demonstrated bioactivity against the important pasture pest black beetle, but can also cause mammalian toxicosis. We genetically modified E. festucae var. lolii strain AR5 to eliminate key enzymatic steps in the ergovaline pathway to determine if intermediate ergot alkaloid compounds can still provide insecticidal benefits in the absence of the toxic end product ergovaline. Four genes (dmaW, easG, cloA, and lpsB) spanning the pathway were deleted and each deletion mutant was inoculated into five different plant genotypes of perennial ryegrass, which were later harvested for a full chemical analysis of the ergot alkaloid compounds produced. These associations were also used in a black beetle feeding deterrence study. Deterrence was seen with just chanoclavine present, but was cumulative as more intermediate compounds in the pathway were made available. Ergovaline was not detected in any of the deletion associations, indicating that bioactivity towards black beetle can be obtained in the absence of this mammalian toxin.


Assuntos
Besouros/fisiologia , Endófitos/genética , Epichloe/genética , Alcaloides de Claviceps/genética , Regulação Fúngica da Expressão Gênica , Lolium/microbiologia , Controle Biológico de Vetores , Animais , Endófitos/metabolismo , Epichloe/metabolismo , Alcaloides de Claviceps/biossíntese , Ergotaminas/metabolismo , Deleção de Genes , Herbivoria , Lolium/parasitologia , Simbiose
7.
Toxins (Basel) ; 14(1)2021 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-35050986

RESUMO

Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate the effects of 24 h exposure to 5-HT and ergot alkaloids (ergovaline, ERV), two assays were conducted. The first assay determined the half-maximal inhibitory concentration (IC50) following the 24 h pre-exposure period, while the second assay evaluated the effect of IC50 concentrations of 5-HT and ERV either individually or in combination. There was an interaction between previous exposure to 5-HT and ERV. Previous exposure to 5-HT at the IC50 concentration of 7.57 × 10-7 M reduced the contractile response by more than 50% of control, while the exposure to ERV at IC50 dose of 1.57 × 10-10 M tended to decrease (p = 0.081) vessel contractility with a response higher than 50% of control. The 24 h previous exposure to both 5-HT and ERV did not potentiate the inhibitory response of blood vessels in comparison with incubation with each compound alone. These results suggest receptor competition between 5-HT and ERV. More studies are necessary to determine the potential of 5-HT to treat toxicosis caused by ergot alkaloids.


Assuntos
Ergotaminas/toxicidade , Micotoxinas/toxicidade , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Bovinos , Feminino
8.
Sci Rep ; 10(1): 9714, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546814

RESUMO

The complex ergot alkaloids, ergovaline and ergotamine, cause dysregulation of physiological functions, characterised by vasoconstriction as well as thermoregulatory and cardiovascular effects in grazing livestock. To assess the effect of the mycotoxins, blood pressure and heart rate of male mice were measured, and metabolite profiling undertaken to determine relative abundances of both ergotamine and its metabolic products in body and brain tissue. Ergotamine showed similar cardiovascular effects to ergovaline, causing elevations in blood pressure and reduced heart rate. Bradycardia was preserved at low-levels of ergovaline despite no changes in blood pressure. Ergotamine was identified in kidney, liver and brainstem but not in other regions of the brain, which indicates region-specific effects of the toxin. The structural configuration of two biotransformation products of ergotamine were determined and identified in the liver and kidney, but not the brain. Thus, the dysregulation in respiratory, thermoregulatory, cardiac and vasomotor function, evoked by ergot alkaloids in animals observed in various studies, could be partially explained by dysfunction in the autonomic nervous system, located in the brainstem.


Assuntos
Alcaloides de Claviceps/metabolismo , Alcaloides de Claviceps/toxicidade , Micotoxinas/toxicidade , Ração Animal/análise , Animais , Pressão Sanguínea/efeitos dos fármacos , Alcaloides de Claviceps/química , Ergotamina/metabolismo , Ergotamina/farmacologia , Ergotamina/toxicidade , Ergotaminas/metabolismo , Ergotaminas/farmacologia , Ergotaminas/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Micotoxinas/metabolismo , Micotoxinas/farmacologia , Toxinas Biológicas/farmacologia , Vasoconstrição/efeitos dos fármacos
9.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31850497

RESUMO

Fescue toxicosis is problematic for growing steers, causing lower DMI and productivity when fed endophyte-infected (E+) tall fescue. A complete understanding of underlying mechanisms of how fescue toxicosis affects growing steers is lacking. Therefore, the overall objective of this multiexperiment study was to determine whether ruminally dosed ergovaline (ERV) affects rumen motility, rumen contents, and eating patterns. In Exp. 1, an 8-h period to assess ruminal motility began 4 h after feeding by monitoring pressure changes using a wireless system for 21 d. Eight ruminally cannulated steers (283 kg BW) were pair fed with alfalfa cubes (1.5 × NEm) and assigned to endophyte free (E-; 0 µg ERV/kg BW/d) or E+ treatment (20 µg ERV/kg BW/d). Overall, E+ steers had more frequent rumen contractions (Seed P = 0.05 and day of feeding P = 0.02). On days 7 to 9, both treatments showed lower frequencies and E- steers had greater amplitude of contractions (P < 0.001) that corresponded with decreased DMI. In Exp. 2, steers remained in pairs assigned in Exp. 1 (322 kg BW), but reversed seed treatments while increasing ERV levels (titrated 0, 5, 10, 15, and 20 µg ERV/kg BW/d over 57 d). There were no differences between E- and E+ for frequency (P = 0.137) or amplitude of contractions (P = 0.951), but increasing ERV dosage, decreased frequency (P = 0.018) and amplitude (P = 0.005), coinciding with lower DMI. In Exp. 3, 8 steers (589 kg) were pair fed and ruminally dosed 15 µg ERV/kg BW/d, and rumen motility data were collected for 21 d. E- steers showed higher amplitude and lower frequency of contractions than E+ steers with seed (P < 0.001), day (P < 0.001), and seed × day (P < 0.04) effects, but rumen fill was not different between E- and E+ (P > 0.29). Serum prolactin concentrations were lower in E+ steers in Exp. 1 to 3. Eating patterns of pair-fed E- and E+ steers were relatively slower in E+ than E- (Exp. 4) by measuring every 2 h across 24 h. Number of meals were higher in E+ than E- steers, but meal duration and meal size were not different between treatments. Rumen content (DM%) tended to be higher in E+ than in E- when steers were fed once a day (P = 0.07), but there was no difference for rumen content (DM%) when E- and E+ steers were fed 12 times a day (P = 0.13). These results suggest the changes in rumen fill associated with fescue toxicosis may be driven more by changes in feeding behavior and eating pattern rather than by changes in motility.


Assuntos
Ergotaminas/efeitos adversos , Comportamento Alimentar/efeitos dos fármacos , Festuca/química , Intoxicação por Plantas/veterinária , Ração Animal/análise , Animais , Bovinos , Digestão , Ingestão de Alimentos , Endófitos , Masculino , Medicago sativa/microbiologia , Prolactina , Distribuição Aleatória , Sementes/microbiologia
10.
Toxins (Basel) ; 11(11)2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703425

RESUMO

The rapid identification and quantitation of alkaloids produced by Epichloë endophyte-infected pasture grass is important for the agricultural industry. Beneficial alkaloids, such as peramine, provide the grass with enhanced insect protection. Conversely, ergovaline and lolitrem B can negatively impact livestock. Currently, a single validated method to measure these combined alkaloids in planta does not exist. Here, a simple two-step extraction method was developed for Epichloë-infected perennial ryegrass (Lolium perenne L.). Peramine, ergovaline and lolitrem B were quantified using liquid chromatography-mass spectrometry (LC-MS). Alkaloid linearity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision, selectivity, recovery, matrix effect and robustness were all established. The validated method was applied to eight different ryegrass-endophyte symbiota. Robustness was established by comparing quantitation results across two additional instruments; a triple quadruple mass spectrometer (QQQ MS) and by fluorescence detection (FLD). Quantitation results were similar across all three instruments, indicating good reproducibility. LOQ values ranged from 0.8 ng/mL to 6 ng/mL, approximately one hundred times lower than those established by previous work using FLD (for ergovaline and lolitrem B), and LC-MS (for peramine). This work provides the first highly sensitive quantitative LC-MS method for the accurate and reproducible quantitation of important endophyte-derived alkaloids.


Assuntos
Endófitos/crescimento & desenvolvimento , Ergotaminas/análise , Compostos Heterocíclicos com 2 Anéis/análise , Alcaloides Indólicos/análise , Lolium/microbiologia , Micotoxinas/análise , Poliaminas/análise , Cromatografia Líquida , Endófitos/química , Ergotaminas/toxicidade , Compostos Heterocíclicos com 2 Anéis/toxicidade , Alcaloides Indólicos/toxicidade , Limite de Detecção , Micotoxinas/toxicidade , Brotos de Planta/microbiologia , Poliaminas/toxicidade , Espectrometria de Massas em Tandem
11.
J Anim Sci ; 97(10): 4160-4170, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31353402

RESUMO

Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue that affects performance; however, little information is available pertaining to its effects on immunity. Recently, it has been shown that supplemental CP can improve performance in weaned steers postvaccination. Thus, the objective of this study was to evaluate the effect of supplemental CP on innate and adaptive immune responses in stocker steers chronically exposed to ergovaline. Angus steers (n = 12 pens; 3 steers/pen) were stratified by weight and assigned to a 2 × 2 factorial arrangement to examine crude protein levels of supplement (14% or 18%) and ergovaline exposure (0 or 185 µg ergovaline/kg BW/d via ground endophyte-free (EF) or endophyte-infected (EI) tall fescue seed, respectively) on immune response. Consumption of low to moderate concentration of ergovaline from EI tall fescue seed was sufficient to induce mild symptoms associated with fescue toxicosis. Blood samples were collected at day 0, 42, and 56 to evaluate infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea virus (BVDV) type 1b titers following vaccine challenge. Additionally, serum cytokine concentrations were evaluated using Quantibody Bovine Cytokine Arrays on day 0, 28, and 42. Data were analyzed using PROC MIXED of SAS with repeated measures. Regardless of treatment, no differences were observed in IBR and BVDV-1b seroconversion following vaccine challenge (P > 0.05). Regardless of crude protein concentration, EI steers had greater concentrations of proinflammatory cytokines (TNF-α, IFN-γ, IL-1α), chemokines (CCL2, CCL4, MIG), anti-inflammatory cytokines (IL-2, -13, -15, -21), and various growth factors (FGF-1, IGF-1, VEGF-A) when compared to EF steers (P < 0.05). Furthermore, VEGF-A and IGF-1 concentrations were greater in EI-14 steers on day 28 compared to EI-18, EF-14, and EF-18 steers (P < 0.05), however, this difference was not observed on day 0 or 42 (P > 0.05). Based on these data, steers exposed to ergovaline have an increase in pro- and anti-inflammatory cytokines and supplemental CP had minimal impact to mitigate this response. However, in the current study, exposure to ergovaline had little to no effect on adaptive immunity and response to vaccination. Together, chronic exposure to ergovaline results in a hyperactive innate immune response, which may lead to an immuno-compromised animal.


Assuntos
Ração Animal/análise , Bovinos/imunologia , Suplementos Nutricionais/análise , Endófitos/fisiologia , Ergotaminas/farmacologia , Festuca/microbiologia , Imunidade Inata , Intoxicação por Plantas/veterinária , Vacinas/imunologia , Animais , Festuca/química , Masculino
12.
J Anim Sci ; 97(7): 3153-3168, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31051033

RESUMO

The objective of this study was to assess how exposure to ergot alkaloids during 2 stages of gestation alters fetal growth, muscle fiber formation, and miRNA expression. Pregnant ewes (n = 36; BW = 83.26 ± 8.14 kg; 4/group; 9 groups) were used in a 2 × 2 factorial arrangement with 2 tall fescue seed treatments [endophyte-infected (E+) vs. endophyte-free (E-)] fed during 2 stages of gestation (MID, days 35 to 85 vs. LATE, days 86 to 133), which created 4 possible treatments (E-/E-, E+/E-, E-/E+, or E+/E+). Ewes were individually fed a total mixed ration containing E+ or E- fescue seed according to treatment assignment. Terminal surgeries were conducted on day 133 of gestation for the collection of fetal measurements and muscle samples. Data were analyzed as a 2 × 2 factorial with fescue treatment, stage of gestation, and 2-way interaction as fixed effects. Fetuses exposed to E+ seed during LATE gestation had reduced (P = 0.0020) fetal BW by 10% compared with E- fetuses; however, fetal body weight did not differ (P = 0.41) with E+ exposure during MID gestation. Fetuses from ewes fed E+ seed during MID and LATE gestation tended to have smaller (P = 0.058) kidney weights compared with E- fetuses. Liver weight was larger (P = 0.0069) in fetuses fed E- during LATE gestation compared with E+. Fetal brain weight did not differ by fescue treatment fed during MID (P = 0.36) or LATE (P = 0.40) gestation. The percentage of brain to empty body weight (EBW) was greater (P = 0.0048) in fetuses from ewes fed E+ fescue seed during LATE gestation, which is indicative of intrauterine growth restriction (IUGR). Primary muscle fiber number was lower (P = 0.0005) in semitendinosus (STN) of fetuses exposed to E+ during MID and/or LATE gestation compared with E-/E-. miRNA sequencing showed differential expression (P < 0.010) of 6 novel miRNAs including bta-miR-652_R+1, mdo-miR-22-3p, bta-miR-1277_R-1, ppy-miR-133a_L+1_1ss5TG, hsa-miR-129-1-3p, and ssc-miR-615 in fetal STN muscle. These miRNA are associated with glucose transport, insulin signaling, intracellular ATP, hypertension, or adipogenesis. This work supports the hypothesis that E+ tall fescue seed fed during late gestation reduces fetal weight and causes asymmetrical growth, which is indicative of IUGR. Changes in primary fiber number and miRNA of STN indicate that exposure to E+ fescue fed during MID and LATE gestation alters fetal muscle development that may affect postnatal muscle growth and meat quality.


Assuntos
Endófitos/fisiologia , Alcaloides de Claviceps/toxicidade , Festuca/química , MicroRNAs/genética , Ovinos/fisiologia , Transcriptoma/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Ergotaminas/toxicidade , Feminino , Festuca/microbiologia , Desenvolvimento Fetal/efeitos dos fármacos , Peso Fetal/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Placentação , Gravidez , Sementes/química , Sementes/microbiologia , Ovinos/crescimento & desenvolvimento
13.
J Anim Sci ; 97(4): 1874-1890, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30895321

RESUMO

Tall fescue [Lolium arundinaceum (Scheyreb.) Darbysh] is the primary cool season forage grass in the Southeastern United States. Most tall fescue contains an endophytic fungus (Epichloë coenophiala) that produces ergot alkaloids and upon ingestion induces fescue toxicosis. The objective of this study was to assess how exposure to endophyte-infected (E+; 1.77 mg hd-1 d-1 ergovaline and ergovalinine) or endophyte-free (E-; 0 mg hd-1 d-1 ergovaline and ergovalinine) tall fescue seed fed during 2 stages of gestation (MID, days 35-85/LATE, days 86-133) alters placental development. Thirty-six, fescue naïve Suffolk ewes were randomly assigned to 1 of 4 fescue treatments: E-/E-, E-/E+, E+/E-, or E+/E+. Ewes were individually fed the same amount of E+ or E- seed mixed into total mixed ration during MID and LATE gestation. Terminal surgeries were conducted on day 133 of gestation. Ewes fed E+ fescue seed had elevated (P < 0.001) ergot alkaloid excretion and reduced (P < 0.001) prolactin levels during the periods when fed E+ seed. Ewes switched on day 86 from E- to E+ seed had a 4% reduction (P = 0.005) in DMI during LATE gestation, which translated to a 2% reduction (P = 0.07) in DMI overall. Average daily gain was also reduced (P = 0.049) by 64% for E-/E+ ewes during LATE gestation and tended to be reduced (P = 0.06) by 33% overall. Ewes fed E+ seed during LATE gestation exhibited a 14% and 23% reduction in uterine (P = 0.03) and placentome (P = 0.004) weights, respectively. Caruncle weights were also reduced by 28% (P = 0.003) for E-/E+ ewes compared with E-/E- and E+/E-. Ewes fed E+ seed during both MID and LATE gestation exhibited a 32% reduction in cotyledon (P = 0.01) weights, whereas ewes fed E+ seed only during MID gestation (E+/E-) had improved (P = 0.01) cotyledon weights. The percentage of type A placentomes tended to be greater (P = 0.08) for E+/E+ ewes compared with other treatments. Other placentome types (B, C, or D) did not differ (P > 0.05). Total fetal weight per ewe was reduced (P = 0.01) for ewes fed E+ seed during LATE gestation compared with E-; however, feeding E+ seed during MID gestation did not alter (P = 0.70) total fetal weight per ewe. These results suggest that exposure to ergot alkaloids during LATE (days 86-133) gestation has the greatest impact on placental development by reducing uterine and placentome weights. This, in turn, reduced total fetal weight per ewe by 15% in ewes fed E+ seed during LATE gestation (E-/E+ and E+/E+).


Assuntos
Epichloe/química , Alcaloides de Claviceps/toxicidade , Festuca/química , Ovinos/fisiologia , Ração Animal , Animais , Endófitos , Epichloe/fisiologia , Ergotaminas/toxicidade , Feminino , Festuca/microbiologia , Placentação/efeitos dos fármacos , Gravidez , Distribuição Aleatória , Ovinos/crescimento & desenvolvimento , Sudeste dos Estados Unidos , Útero/crescimento & desenvolvimento , Útero/fisiologia
14.
J Anim Sci ; 97(4): 1891-1902, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30763439

RESUMO

Previous research has shown that livestock exposed to ergot alkaloids results in decreased vasoactivity of gastrointestinal and peripheral vasculature. Little is known regarding the effect ergot alkaloid exposure during gestation may have on vasculature supporting the fetus. The objective of this study was to evaluate contractile responses of uterine and umbilical arteries collected from ewes consuming ergot alkaloids during gestation. On day 35 of gestation, 36 Suffolk ewes (78.24 ± 9.5 kg) were assigned to endophyte-infected (E+) or endophyte-free (E-) tall fescue seed treatments that were fed either throughout or switched on day 86 of gestation, creating four seed treatments E+E+, E+E-, E-E+, and E-E-. Ewes were fed E+ tall fescue seed to provide 1.77 mg of total ergovaline ⋅ hd-1 ⋅ d-1 with E- ewes receiving the same quantity of E- seed. Gestation was terminated on day 133, and sections of uterine artery and umbilical cord were surgically collected. Only collections from 28 ewes (n = 7/treatment) were of sufficient viability to proceed with the contractility experiments. Arteries were cleaned, sliced into 2-mm cross sections, and suspended in multi-myograph chambers containing 5 mL of continuously oxygenated Krebs-Henseleit buffer. Vessels were exposed to increasing concentrations (5 × 10-8 to 1 × 10-4 M) of norepinephrine, serotonin, ergotamine, and ergovaline (5 × 10-9 to 1 × 10-5M; extract of tall fescue seed) in 15-min intervals. Increasing concentrations of norepinephrine generated a contractile response by the uterine artery (P < 0.05), but no response in the umbilical artery. Increasing concentrations of serotonin resulted in negligible responses in uterine preparations, whereas umbilical artery preparations were responsive (P < 0.05) to serotonin. Ewes receiving E+E+ and E-E+ treatments had decreased vasoactivity in umbilical arteries to serotonin with a dextral shift in concentrations where the response curve initiated (P < 0.05). Interestingly, uterine arteries were not responsive to exposure to ergotamine or ergovaline, whereas umbilical arteries were responsive (P < 0.05). Umbilical arteries collected from ewes receiving E-E- and E+E- were more vasoactive to ergot alkaloids (P < 0.05) than other treatments. These findings indicate that maternal blood supply to the placenta appears protected from negative effects of ergot alkaloids; however, umbilical vasculature is not, and this could adversely influence fetal growth.


Assuntos
Endófitos/química , Alcaloides de Claviceps/toxicidade , Festuca/química , Contaminação de Alimentos , Ovinos/crescimento & desenvolvimento , Ração Animal/análise , Animais , Dieta/veterinária , Endófitos/fisiologia , Ergotamina/toxicidade , Ergotaminas/toxicidade , Feminino , Festuca/microbiologia , Placenta/irrigação sanguínea , Placenta/efeitos dos fármacos , Gravidez , Ovinos/fisiologia , Artérias Umbilicais/efeitos dos fármacos , Artéria Uterina/efeitos dos fármacos , Útero/irrigação sanguínea , Útero/efeitos dos fármacos
15.
Xenobiotica ; 49(10): 1149-1157, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30623698

RESUMO

1. Ergopeptine alkaloids like ergovaline and ergotamine are suspected to be associated with fescue toxicosis and ergotism in horses. Information on the metabolism of ergot alkaloids is scarce, especially in horses, but needed for toxicological analysis of these drugs in urine/feces of affected horses. The aim of this study was to investigate the metabolism of ergovaline, ergotamine, ergocristine, and ergocryptine in horses and comparison to humans. 2. Supernatants of alkaloid incubations with equine and human liver S9 fractions were analyzed by reversed-phase liquid-chromatography coupled to high-resolution tandem mass spectrometry with full scan and MS2 acquisition. Metabolite structures were postulated based on their MS2 spectra in comparison to those of the parent alkaloids. All compounds were extensively metabolized yielding nor-, N-oxide, hydroxy and dihydro-diole metabolites with largely overlapping patterns in equine and human liver S9 fractions. However, some metabolic steps e.g. the formation of 8'-hydroxy metabolites were unique for human metabolism, while formation of the 13/14-hydroxy and 13,14-dihydro-diol metabolites were unique for equine metabolism. Incubations with equine whole liver preparations yielded less metabolites than the S9 fractions. 3. The acquired data can be used to develop metabolite-based screenings for these alkaloids, which will likely extend their detection windows in urine/feces from affected horses.


Assuntos
Ergolinas , Ergotamina , Ergotaminas , Fígado/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Ergolinas/farmacocinética , Ergolinas/farmacologia , Ergotamina/farmacocinética , Ergotamina/farmacologia , Ergotaminas/farmacocinética , Ergotaminas/farmacologia , Cavalos , Humanos , Espectrometria de Massas em Tandem
16.
J Anim Sci ; 96(11): 4912-4922, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30476153

RESUMO

Ergot alkaloids from endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum) induce vasoconstriction. Previous work has shown that serotonin receptor subtype, 5HT2A, is present in bovine ruminal (R) and mesenteric (M) vasculature, plays a role in vasoconstriction, and could be influenced by ergot alkaloids. To determine the influence of ergot alkaloids on 5HT2A, the vasoactivity of an agonist selective for 5HT2A, (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine HCl (TCB-2), was evaluated using bovine ruminal and mesenteric arteries and veins (RA, RV, MA, MV) that were exposed to ergovaline (ERV) prior to or during the TCB-2 additions. Ruminal and mesenteric blood vessel segments were collected, cleaned, and cut into 2- to 3-mm cross-sections. Vessel segments were incubated in Krebs-Henseleit buffer containing 0, 0.01 or 1 µM ERV for 2 h prior to TCB-2 dose response or exposed to ERV concentrations simultaneously during TCB-2 dose response. For the dose response portion of the study, vessels were suspended in a multimyograph containing 5 mL of continuously oxygenated Krebs-Henseleit buffer and equilibrated to 1 g tension for 90 min. Vessels were exposed to increasing concentrations of TCB-2 every 15 min and contractile response data were normalized as a percentage of the maximum contractile response induced by 120 mM KCl reference. Analysis of variance was evaluated separately for each vessel and each ERV exposure experiment using the mixed models procedure of SAS for effects of TCB-2 and ERV concentrations. All blood vessels with previous ERV exposure had significantly lower contractile responses to TCB-2 (P < 0.01). All blood vessels with simultaneous exposure to 1 µM ERV had higher (P < 0.01) contractile responses at lower concentrations of TCB-2. Simultaneous ERV addition at 1 × 10-4 M TCB-2 did not affect contractility of RV, MA, MV (P > 0.05), but decreased contractility of RA (P < 0.01). These results indicate that ergopeptine alkaloid exposure influences contractility of bovine ruminal and mesenteric blood vessels through serotonin receptor subtype 5HT2A by acting as both an agonist and antagonist. Additional work is needed to determine if ergot alkaloids like ERV simply occupy receptor binding sites competitively, or influence receptor internalization to cause the observed divergent responses.


Assuntos
Bovinos/fisiologia , Epichloe/fisiologia , Ergotaminas/metabolismo , Festuca/química , Receptor 5-HT2A de Serotonina/metabolismo , Vasoconstrição/efeitos dos fármacos , Animais , Endófitos/química , Alcaloides de Claviceps/metabolismo , Festuca/microbiologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos
17.
PLoS One ; 13(10): e0201866, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30335760

RESUMO

Negative impacts of endophyte-infected Lolium arundinaceum (Darbyshire) (tall fescue) are responsible for over $2 billion in losses to livestock producers annually. While the influence of endophyte-infected tall fescue has been studied for decades, mitigation methods have not been clearly elucidated. Isoflavones found in Trifolium pratense (red clover) have been the subject of recent research regarding tall fescue toxicosis mitigation. Therefore, the aim of this study was to determine the effect of ergovaline and red clover isoflavones on rumen microbial populations, fiber degradation, and volatile fatty acids (VFA) in an in vitro system. Using a dose of 1.10 mg × L-1, endophyte-infected or endophyte-free tall fescue seed was added to ANKOM fiber bags with or without 2.19 mg of isoflavones in the form of a control, powder, or pulverized tablet, resulting in a 2 × 3 factorial arrangements of treatments. Measurements of pH, VFA, bacterial taxa, as well as the disappearance of neutral detergent fiber (aNDF), acid detergent fiber (ADF), and crude protein (CP) were taken after 48 h of incubation. aNDF disappearance values were significantly altered by seed type (P = 0.003) and isoflavone treatment (P = 0.005), and ADF disappearance values were significantly different in a seed × isoflavone treatment interaction (P ≤ 0.05). A seed × isoflavone treatment interaction was also observed with respect to CP disappearance (P ≤ 0.05). Eighteen bacterial taxa were significantly altered by seed × isoflavone treatment interaction groups (P ≤ 0.05), eight bacterial taxa were increased by isoflavones (P ≤ 0.05), and ten bacterial taxa were altered by seed type (P ≤ 0.05). Due to the beneficial effect of isoflavones on tall fescue seed fiber degradation, these compounds may be viable options for mitigating fescue toxicosis. Further research should be conducted to determine physiological implications as well as microbiological changes in vivo.


Assuntos
Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Lolium/efeitos dos fármacos , Rúmen/microbiologia , Ração Animal , Animais , Bactérias/classificação , Bactérias/genética , Bovinos , Fibras na Dieta/metabolismo , Ergotaminas/administração & dosagem , Ácidos Graxos Voláteis , Fermentação/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Isoflavonas/administração & dosagem , Isoflavonas/química , Lolium/crescimento & desenvolvimento , Lolium/metabolismo , Proteínas/química , Rúmen/química , Rúmen/metabolismo , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Trifolium/química
18.
J Anim Sci ; 96(11): 4812-4822, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30102353

RESUMO

Fescue toxicosis is a syndrome that impairs growth and reproduction in cattle grazing endophyte-infected tall fescue [Lolium arundinaceum [(Schreb.].) Darbysh)] in the United States, resulting in approximately $1 billion in annual economic loss in species that utilize this forage resource. Approximately 90% of tall fescue contains an endophytic fungus (Epichloë coenophiala) that produces ergot alkaloids. Ergot alkaloids cause vasoconstriction and reduced blood flow to the extremities; however, it remains unknown how blood flow to the reproductive organs is affected in cattle. Therefore, the objective of this study was to determine if ergot alkaloids from endophyte-infected tall fescue reduce blood flow to the reproductive organs, thus hindering reproductive function. Angus heifers (n = 36) naïve to ergot alkaloids were placed in Calan gates and randomly assigned to receive either endophyte-infected fescue seed (E+) or noninfected fescue seed (E-; control) in a total mixed ration for 63 d. Weekly measurements were taken to monitor heifer growth and response to ergot alkaloid exposure. Reproductive measurements, including ovarian structures, uterine and ovarian vessel diameter, and hormone concentrations were determined after heifers were synchronized using the standard CO-Synch + 7 d CIDR protocol to ensure all measurements were collected at the same stages of the estrous cycle (0, 4, 10, and 17 d). Data were analyzed using repeated measures in PROC MIXED of SAS. Average daily gain was decreased for the E+ group (0.8 kg/d) compared to control heifers (1.0 kg/d). Body condition scores tended to be greater in control heifers compared to the E+ group (P = 0.053). Additionally, hair coat and hair shedding scores were greater in E+ heifers compared to controls (P < 0.05). Heart rate, rectal temperature, respiration rate, and blood pressure did not differ between treatments (P > 0.05). Vasoconstriction was observed in the caudal artery, but not the caudal vein, in heifers consuming the E+ fescue seed (P < 0.05). No differences were observed in antral follicle counts, corpus luteum area or circulating progesterone concentrations in E+ heifers compared to controls (P > 0.05). There was a significant decrease in the diameter of arteries and veins servicing the ovary and uterus on day 10 and 17 of the estrous cycle. Reduction in blood flow to the reproductive organs during critical times in the estrous cycle may contribute to the reduced ovarian function and pregnancy rates associated with fescue toxicosis.


Assuntos
Bovinos/fisiologia , Epichloe/fisiologia , Alcaloides de Claviceps/farmacologia , Festuca/química , Reprodução/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Endófitos , Alcaloides de Claviceps/química , Ergotaminas , Ciclo Estral/efeitos dos fármacos , Feminino , Festuca/microbiologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Ovário/irrigação sanguínea , Gravidez , Distribuição Aleatória , Útero/irrigação sanguínea
19.
Prensa méd. argent ; 104(6): 303-311, Ago2018. fig
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1051369

RESUMO

Case report of a patient with ergotism. ergotism is a complication of acute intoxication of chronic abuse of ergot derivates. Ergot is a fungus that grows on rye and less commonly on other grases such as wheat. Ergotism is a severe reaction to ergocontaminated food (such as rye bread). Ergot refers to a group of fungi of the genus Claviceps. It is a condition that develops of longterm ingestion of ergotamines. In excess, ergotamine can cause symptos such as hallucinations, severe gastrointestinal upset, a type-of dry gangrene and a pain-ful sensation in the extremities. Our patient is presented with anterior unilateral ischemic optic neuropathy. The studies performed and the clinical evaluatiion, are presented, and the treatment the same as the follow-up, are described in the article.


Assuntos
Humanos , Adulto , Ergotismo/diagnóstico , Neuropatia Óptica Isquêmica/terapia , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Interações Medicamentosas , Ergotaminas/efeitos adversos , Ergotaminas/uso terapêutico , Uso Indevido de Medicamentos
20.
Transgenic Res ; 27(5): 397-407, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30030680

RESUMO

Alkaloid concentration of perennial ryegrass herbage is affected by endophyte strain and host plant genotype. However, previous studies suggest that associations between host and endophyte also depends on environmental conditions, especially those affecting nutrient reserves and that water-soluble carbohydrate (WSC) concentration of perennial ryegrass plants may influence grass-endophyte associations. In this study a single transgenic event, with altered expression of fructosyltransferase genes to produce high WSC and biomass, has been crossed into a range of cultivar backgrounds with varying Epichloë endophyte strains. The effect of the association between the transgenic trait and alkaloid production was assessed and compared with transgene free control populations. In the vast-majority of comparisons there was no significant difference between alkaloid concentrations of transgenic and non-transgenic plants within the same cultivar and endophyte backgrounds. There was no significant difference between GOI+ (gene of interest positive) and GOI- (gene of interest negative) populations in Janthritrem response. Peramine concentration was not different between GOI+ and GOI- for 10 of the 12 endophytes-cultivar combinations. Cultivar Trojan infected with NEA6 and Alto with SE (standard endophyte) exhibited higher peramine and lolitrem B (only for Alto SE) concentration, in the control GOI- compared with GOI+. Similarly, cultivar Trojan infected with NEA6 and Alto with NEA3 presented higher ergovaline concentration in GOI-. Differences in alkaloid concentration may be attributable to an indirect effect in the modulation of fungal biomass. These results conclude that the presence of this transgenic insertion, does not alter the risk (toxicity) of the endophyte-grass associations. Endophyte-host interactions are complex and further research into associations with high WSC plant should be performed in a case by case basis.


Assuntos
Alcaloides/metabolismo , Endófitos/metabolismo , Epichloe/metabolismo , Hexosiltransferases/genética , Lolium/microbiologia , Micotoxinas/metabolismo , Ração Animal , Endófitos/fisiologia , Epichloe/fisiologia , Ergotaminas/metabolismo , Regulação da Expressão Gênica de Plantas , Compostos Heterocíclicos com 2 Anéis/metabolismo , Hexosiltransferases/metabolismo , Alcaloides Indólicos/metabolismo , Lolium/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Poliaminas/metabolismo
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