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1.
Sci Rep ; 10(1): 9714, 2020 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-32546814

RESUMEN

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.


Asunto(s)
Alcaloides de Claviceps/metabolismo , Alcaloides de Claviceps/toxicidad , Micotoxinas/toxicidad , Alimentación Animal/análisis , Animales , Presión Sanguínea/efectos de los fármacos , Alcaloides de Claviceps/química , Ergotamina/metabolismo , Ergotamina/farmacología , Ergotamina/toxicidad , Ergotaminas/metabolismo , Ergotaminas/farmacología , Ergotaminas/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Micotoxinas/metabolismo , Micotoxinas/farmacología , Toxinas Biológicas/farmacología , Vasoconstricción/efectos de los fármacos
2.
J Anim Sci ; 97(4): 1891-1902, 2019 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-30763439

RESUMEN

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.


Asunto(s)
Endófitos/química , Alcaloides de Claviceps/toxicidad , Festuca/química , Contaminación de Alimentos , Ovinos/crecimiento & desarrollo , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Endófitos/fisiología , Ergotamina/toxicidad , Ergotaminas/toxicidad , Femenino , Festuca/microbiología , Placenta/irrigación sanguínea , Placenta/efectos de los fármacos , Embarazo , Ovinos/fisiología , Arterias Umbilicales/efectos de los fármacos , Arteria Uterina/efectos de los fármacos , Útero/irrigación sanguínea , Útero/efectos de los fármacos
3.
Toxins (Basel) ; 10(2)2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29385697

RESUMEN

Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50) (-log [ETA]) of 6.66 ± 0.17 M). Although sample preparation time affected contractile response (p < 0.001), pre-myograph incubation temperature (39 vs. 21 °C, 1 h) had no effect (p > 0.05). Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg-1 and affinity between 0.51 and 0.57 mg (R²: 0.83-0.92) for both polymers, with no significant difference between polymers (p > 0.05). No significant differences in maximum inhibitory (p = 0.96) and IC50 responses (p = 0.163) between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R² = 0.87, p < 0.01), for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media.


Asunto(s)
Ergotamina/química , Ergotamina/toxicidad , Metacrilatos/química , Vena Safena/efectos de los fármacos , Vasoconstrictores/química , Vasoconstrictores/toxicidad , Adsorción , Animales , Bovinos , Técnicas In Vitro , Impresión Molecular , Vena Safena/fisiología
4.
Reprod Biol ; 5(2): 137-50, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16100563

RESUMEN

Two experiments were performed to determine whether administration of ergotamine tartrate altered embryo development (Exp. 1) and uterine competency to establish pregnancy (Exp. 2) in beef cattle. Animals were fed daily either 0 (CON) or 40 mug/kg body weight of ergotamine tartrate (ERGOT). Following a 30-d period on respective diets, animals in Exp. 1 were artificial inseminated at estrus (d = 0) and single embryo recoveries performed on day 7; whereas, animals in Exp. 2 received two frozen-thawed embryos on day 7. As an indicator of ergotamine effects, prolactin was decreased throughout both experiments in ERGOT compared to CON animals (p<0.05). Furthermore, rectal temperature (RT) tended to increase during both experiments in ERGOT compared to CON (p= 0.06). In Exp. 1, embryo recovery (p=0.08) and the percentage of transferable embryos (p=0.09) tended to be greater for CON than for ERGOT. Percentage of embryos that developed to compacted morula or greater was increased for CON compared to ERGOT heifers (p<0.05). In Exp. 2, pregnancy rates of transferred embryos did not differ between treatment groups. Thus, administration of ERGOT to simulate fescue toxicosis altered developmental potential of embryos, but does not appear to affect uterine competency to establish pregnancy.


Asunto(s)
Bovinos/embriología , Embrión de Mamíferos/efectos de los fármacos , Embrión de Mamíferos/fisiología , Ergotamina/administración & dosificación , Desarrollo Fetal/efectos de los fármacos , Poaceae/microbiología , Animales , Temperatura Corporal , Dieta , Transferencia de Embrión/veterinaria , Ergotamina/toxicidad , Femenino , Modelos Biológicos , Poaceae/efectos adversos , Embarazo , Prolactina/sangre , Útero/efectos de los fármacos , Útero/fisiología
5.
Theriogenology ; 63(5): 1407-18, 2005 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-15725447

RESUMEN

Sixteen yearling bulls were utilized to investigate administration of ergotamine tartrate on semen parameters, fertilization, and endocrinology. Bulls were allotted to a control diet of cracked corn, corn silage, and soybean meal (CON, n = 8) or a diet supplemented daily with 40 microg/kg body weight of ergotamine tartrate (ET, n = 8). Blood samples, average daily gain, scrotal circumference and rectal temperatures were collected every 14 day. Semen samples were obtained every 60 day and evaluated for motility and morphology. Scrotal temperatures were obtained by thermography immediately before electroejaculation. Semen from a subset of bulls from each treatment was also evaluated for in vitro fertilization. Administration of ET increased rectal temperature and resulted in lower scrotal temperatures compared to CON bulls (P < 0.05). However, prolactin, scrotal circumference, testosterone, and semen motility and morphology did not differ between groups throughout the experimental period (224 day). Cleavage rates of embryos derived from in vitro fertilization (IVF) with semen of bulls, fed with ET, were reduced compared to CON (P < 0.05); however, development of cleaved embryos to blastocyst did not differ between treatments. In conclusion, extended exposure of bulls to ET appeared to reduce fertilization potential of sperm.


Asunto(s)
Bovinos/fisiología , Ergotamina/toxicidad , Fertilidad/efectos de los fármacos , Animales , Temperatura Corporal , Fase de Segmentación del Huevo , Dieta , Desarrollo Embrionario , Fertilización In Vitro/veterinaria , Masculino , Prolactina/sangre , Escroto/anatomía & histología , Escroto/fisiología , Motilidad Espermática , Espermatozoides/anomalías , Testosterona/sangre
6.
Vet Immunol Immunopathol ; 61(2-4): 305-16, 1998 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-9613443

RESUMEN

Acremonium coenophialum produces ergopeptide alkaloids in tall fescue (Festuca arundinacea Schreb.). These ergot alkaloids decrease serum alkaline phosphatase (ALP) activity, serum cholesterol and prolactin concentrations, as well as average daily gains (ADG) in cattle. The objective of this study was to evaluate the protection of anti-ergotamine antibodies induced by either oral or parenteral vaccination with protein-ergotamine conjugates or passive vaccination with anti-ergovaline, monoclonal antibodies in a murine model of fescue toxicosis. Ergotamine (EG) was conjugated to bovine serum albumin (BSA) and cholera toxin subunit B (CTB) by the Mannich reaction. Mice were blocked based on weight and randomly allocated into five groups of 10 mice each. Treatment groups were as follows: (1) group vaccinated intraperitoneally (ip) with a BSA-EG conjugate and fed an endophyte-infected (EI) fescue diet (BSA-EG group); (2) group orally vaccinated with a CTB-EG conjugate mixed with free cholera toxin (CT) and fed an EI fescue diet (CTB-EG group); (3) nonvaccinated group fed an EI fescue diet (EI group); (4) group passively vaccinated with anti-ergovaline, monoclonal antibodies and fed an EI fescue diet (MoAB group); and (5) nonvaccinated group fed an endophyte-free (EF) fescue diet (EF group). The EI diet contained 1.5 ppm of Ergovaline (EV), whereas no EV was detected in the EF diet.Respective diets were similar upon nutritional analysis. Unvaccinated mice in the EI group exhibited features of fescue toxicosis as indicated by decreased serum ALP activity and cholesterol, and decreased weight gain as compared to mice in the EF group. Antibodies against EG and EV were present in sera of mice in the BSA-EG and MoAB groups, respectively. Mice orally vaccinated with the CTB-EG conjugate developed secretory IgA (sIgA) antibodies and short-lived, systemic IgG responses against EG. Weight gains were increased in the BSA-EG and CTB-EG groups and tended to be increased in the MoAB group vs. the unvaccinated EI group. Serum ALP activity was decreased in the BSA-EG and MoAB groups as compared to the EF group. Serum ALP activity was further decreased in the BSA-EG vaccinated group as compared to the EI group. Cholesterol concentrations were decreased in the EI, BSA-EG and MoAB groups as compared to the EF group. Prolactin concentrations were similar in all groups.


Asunto(s)
Ergotamina/inmunología , Ergotamina/toxicidad , Plantas Tóxicas/toxicidad , Poaceae/toxicidad , Acremonium/patogenicidad , Administración Oral , Fosfatasa Alcalina/sangre , Animales , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/prevención & control , Toxina del Cólera/administración & dosificación , Colesterol/sangre , Ergotamina/administración & dosificación , Inmunoglobulina A Secretora/biosíntesis , Inmunoglobulina G/biosíntesis , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos BALB C , Plantas Tóxicas/inmunología , Plantas Tóxicas/microbiología , Poaceae/inmunología , Poaceae/microbiología , Prolactina/sangre , Albúmina Sérica Bovina/administración & dosificación , Vacunación/veterinaria , Aumento de Peso
7.
Food Chem Toxicol ; 30(8): 731-4, 1992 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1398355

RESUMEN

The effect of dietary ergotamine on pre-lesional indicators of atherosclerosis was studied in rabbits. The experimental purified diets contained 0.08% (w/w) cholesterol and either 0, 40 or 200 mg ergotamine-tartrate/kg. After 6 wk, serum total cholesterol concentration and the ratio of serum total cholesterol: high-density lipoprotein-cholesterol were significantly increased by ergotamine in a dose-dependent manner. Dietary ergotamine raised the total level of glycosaminoglycans and the relative proportion of chondroitin sulphate in the abdominal aorta. It is suggested that dietary ergotamine is atherogenic in the rabbit.


Asunto(s)
Arteriosclerosis/inducido químicamente , Ergotamina/toxicidad , Animales , Aorta/química , Colesterol/sangre , Dieta , Relación Dosis-Respuesta a Droga , Lipoproteínas HDL/sangre , Conejos
8.
J Toxicol Environ Health A ; 58(3): 145-55, 1999 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-10522646

RESUMEN

The ergopeptine alkaloid ergotamine (ET) mimics the effects of ergopeptine alkaloids found in endophyte-infected (E+) fescue forage considered causative for fescue toxicosis. Altered immune capacity, compromised intake and thermoregulation, and inflammatory changes are observed in fescue toxicosis. Taken together, these suggest the cytokine pattern may be altered by ergot alkaloids. Thus, the objective of this study was to determine whether major splenocyte-derived cytokines--interleukin 2 (IL-2), interleukin 4 (IL-4), interferon gamma (IFN-gamma)--and macrophage-derived cytokines--interleukin 1beta, (IL-1beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha)--were affected by ergotamine. Two sets of male BALB/c mice (n = 5/treatment) were treated with ergotamine tartrate (s.c.) for 10 d at doses of 0 (control), 0.4, 2, 10, or 50 mg/kg body weight. Twenty-four hours after the last treatment, splenocytes (S) were isolated from one set of animals and macrophages (Mphi) from the other set for determination of IL-2, IL-4, INF-gamma, and IL-1beta, IL-6, TNF-alpha, respectively. Following activation with 5 microg/ml concanavalin A (Con A) (S) and 10 microg/ml lipopolysaccharide (LPS) (Mphi), cells were incubated for 48 and 24 h, respectively, and supernatants were collected and assayed for respective cytokines by enzyme-linked immunosorbent assay (ELISA). Additionally, differential white blood cell (WBC) counts were performed and the neutrophil (N):lymphocyte (L) ratio calculated. Ergotamine treatment significantly increased IL-6 levels at the 2.0 mg/kg dose and greater and TNF-alpha at the highest dose. There was no treatment effect on IL-1beta, IL-2, IL-4, and IFN-gamma. Also, no effect was observed upon total and differential WBC counts as well as N:L ratio. Ergotamine affected the proinflammatory cytokine IL-6, and this increase may contribute to fescue tosicosis.


Asunto(s)
Citocinas/biosíntesis , Ergotamina/toxicidad , Inflamación/metabolismo , Micotoxinas/toxicidad , Animales , Recuento de Células Sanguíneas , Recuento de Células , Inflamación/inducido químicamente , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Interleucina-4/biosíntesis , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis
9.
J Anim Sci ; 76(6): 1644-50, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9655585

RESUMEN

Plasma samples from two experiments were processed to determine whether ergot alkaloids associated with endophyte-infected tall fescue altered peripheral thyroxine (T4), triiodothyronine (T3), or cortisol concentrations in cattle. In Exp. 1, seven Angus steers (294 kg) received i.v. bolus injections of saline (SAL), ergonovine maleate (7 mg; EM), or ergotamine tartrate (7 mg; ET) at weekly intervals, and they received all treatments during the study. Blood was sampled every 15 min for 5 h, and treatments were given after h 1. Mean ambient temperature was 34 degrees C. Treatment x time affected plasma concentrations of T3 (P < .05) and of cortisol (P < .001) but not that of T4 (P > .2). Plasma T3 concentrations were not affected by SAL, whereas concentrations increased (P < .01) after either EM or ET treatment. Plasma cortisol concentrations were not altered by SAL or EM, but they were increased (P < .001) by ET treatment. In Exp. 2, six Holstein cows (499 kg) nursing calves received a bolus i.v. injection of SAL, EM (9.5 mg), or ET (9.5 mg) per estrous cycle, and all treatments were given over three cycles. Blood was sampled every 20 min for 5 h; treatments were given after h 1. Mean ambient temperature was 26 degrees C. Treatment x time affected T3 (P = .08) and cortisol (P < .001) and tended to influence (P = .16) T4 concentrations. Plasma T3, T4, and cortisol concentrations were not influenced by SAL treatment. Plasma T3 was higher (P < or = .01) after EM or ET treatment compared with pretreatment concentrations. Concentrations of T4 during the 4 h after EM and ET were increased (P < .001) compared with pretreatment. Plasma cortisol concentrations were not altered by EM but were increased (P < .001) by ET. Ergot alkaloids implicated as contributing agents to fescue toxicosis alter plasma concentrations of hormones important to metabolic and thermoregulatory functions in cattle.


Asunto(s)
Bovinos/metabolismo , Ergonovina/toxicidad , Ergotamina/toxicidad , Hidrocortisona/sangre , Tiroxina/sangre , Triyodotironina/sangre , Animales , Bovinos/sangre , Estudios Cruzados , Ergonovina/administración & dosificación , Ergotamina/administración & dosificación , Femenino , Inyecciones Intravenosas/veterinaria , Masculino , Factores de Tiempo
10.
J Anim Sci ; 79(2): 542-9, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11219466

RESUMEN

Ergot alkaloids cause fescue toxicosis when livestock graze endophyte-infected tall fescue. It is generally accepted that ergovaline is the toxic component of endophyte-infected tall fescue, but there is no direct evidence to support this hypothesis. The objective of this study was to examine relative and potential transport of ergoline and ergopeptine alkaloids across isolated gastric tissues in vitro. Sheep ruminal and omasal tissues were surgically removed and placed in parabiotic chambers. Equimolar concentrations of lysergic acid, lysergol, ergonovine, ergotamine, and ergocryptine were added to a Kreb's Ringer phosphate (KRP) solution on the mucosal side of the tissue. Tissue was incubated in near-physiological conditions for 240 min. Samples were taken from KRP on the serosal side of the chambers at times 0, 30, 60, 120, 180, and 240 min and analyzed for ergot alkaloids by competitive ELISA. The serosal KRP remaining after incubation was freeze-dried and the alkaloid species quantified by HPLC. The area of ruminal and omasal tissues was measured and the potential transportable alkaloids calculated by multiplying the moles of transported alkaloids per square centimeter of each tissue type by the surface area of the tissue. Studies were conducted to compare alkaloid transport in reticular, ruminal, and omasal tissues and to determine whether transport was active or passive. Ruminal tissue had greater ergot alkaloid transport potential than omasal tissue (85 vs 60 mmol) because of a larger surface area. The ruminal posterior dorsal sac had the greatest potential for alkaloid transport, but the other ruminal tissues were not different from one another. Alkaloid transport was less among reticular tissues than among ruminal tissues. Transport of alkaloids seemed to be an active process. The alkaloids with greatest transport potential were lysergic acid and lysergol. Ergopeptine alkaloids tended to pass across omasal tissues in greater quantities than across ruminal tissues, but their transport was minimal compared to lysergic acid and lysergol.


Asunto(s)
Alcaloides de Claviceps/farmacocinética , Omaso/metabolismo , Rumen/metabolismo , Ovinos/metabolismo , Animales , Transporte Biológico , Ergolinas/farmacocinética , Ergolinas/toxicidad , Ergonovina/farmacocinética , Ergonovina/toxicidad , Ergotamina/farmacocinética , Ergotamina/toxicidad , Femenino , Absorción Intestinal , Modelos Lineales , Ácido Lisérgico/farmacocinética , Ácido Lisérgico/toxicidad , Distribución Aleatoria , Reticulum/fisiología , Azida Sódica/farmacología
11.
J Anim Sci ; 76(5): 1448-54, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9621953

RESUMEN

We conducted research to evaluate whether ergot alkaloids associated with endophyte-infected tall fescue could alter plasma concentrations of hormones important to reproductive function in cows. Six primiparous, estrous-cycling Holstein cows nursing calves received single i.v. injections of ergotamine tartrate, ergonovine maleate, or saline vehicle in a simple cross-over design. Each cow received one compound per estrous cycle, d 15 or 16 after estrus, and all compounds over three estrous cycles. Blood samples were collected at 20-min intervals for 40 min before and 240 min after treatments to assess plasma concentrations of prolactin, LH, FSH, and the response by PGF2alpha metabolite 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Ambient temperature and respiratory rates were measured hourly. Ambient temperature averaged 26 degrees C during data collection. Treatment x time was a significant source of variation for respiration rate and plasma concentrations of every hormone evaluated except FSH. Ergotamine elevated (P < .01) respiration rates 2 to 4 h after treatment. Ergotamine and ergonovine reduced (P < .001) plasma concentrations of prolactin for 2 to 4 h after treatment compared to concentrations before treatment. Plasma concentrations of LH were lowered (P < .01) by ergonovine during the 3rd h after treatment and by ergotamine during the 4th h after treatment. Most cows exhibited secretory PGFM responses after ergotamine and ergonovine treatments compared with an absence of a PGFM response in all cows after saline (P < or = .01). Results indicated that ergot alkaloids implicated as causative agents for fescue toxicosis can alter plasma concentrations of reproductive hormones during the late luteal phase of the estrous cycle in cows.


Asunto(s)
Bovinos/sangre , Ergonovina/toxicidad , Ergotamina/toxicidad , Gonadotropinas Hipofisarias/sangre , Reproducción/fisiología , Animales , Bovinos/fisiología , Estudios Cruzados , Dinoprost/análogos & derivados , Dinoprost/sangre , Dinoprost/metabolismo , Femenino , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Prolactina/sangre , Reproducción/efectos de los fármacos , Respiración/efectos de los fármacos , Estaciones del Año
12.
J Anim Sci ; 70(9): 2838-46, 1992 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1328128

RESUMEN

The possibility of supplementing livestock diets with an aluminosilicate to protect them from fescue toxicosis was investigated. An in vitro study showed that hydrated sodium calcium aluminosilicate (HSCAS) removed greater than 90% of the ergotamine from aqueous solutions at pH 7.8 or lower, indicating a high affinity of ergotamine for HSCAS in vitro. Rats fed diets containing tall fescue seed infested (E+) with the endophytic fungus Acremonium coenophialum had lower (P less than .05) feed intakes and weight gains than did rats fed diets containing uninfested (E-) tall fescue seed. When feed intake by rats fed the E- seed diet was limited to that of rats fed the E+ seed diet, weight gains did not differ, but testes weights and serum prolactin (PRL) concentrations were lower (P less than .05 and .10, respectively) in rats receiving E+ seed. Supplementing E+ seed diets with HSCAS did not eliminate effects of E+ seed on intake, PRL, or testes weights. Sheep fed E+ tall fescue hay had higher (P less than .05) rectal temperatures than did sheep fed an equal amount of E- tall fescue hay, but OM and N digestion coefficients did not differ between the two hays. Supplementing E+ hay diets with HSCAS did not eliminate the effect of E+ hay on rectal temperatures. Addition of 2% HSCAS to tall fescue hay diets did not affect apparent absorption by sheep of OM, N, Ca, P, Na, K, or Cu, but it reduced (P less than .05) the apparent absorption of Mg, Mn, and Zn.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Silicatos de Aluminio/uso terapéutico , Minerales/farmacocinética , Intoxicación por Plantas/veterinaria , Poaceae , Enfermedades de las Ovejas/prevención & control , Absorción/efectos de los fármacos , Acremonium/crecimiento & desarrollo , Acremonium/metabolismo , Silicatos de Aluminio/farmacología , Animales , Digestión , Ingestión de Alimentos , Ergotamina/aislamiento & purificación , Ergotamina/envenenamiento , Ergotamina/toxicidad , Concentración de Iones de Hidrógeno , Riñón/crecimiento & desarrollo , Hígado/crecimiento & desarrollo , Masculino , Tamaño de los Órganos , Intoxicación por Plantas/prevención & control , Poaceae/microbiología , Prolactina/sangre , Ratas , Ratas Sprague-Dawley , Ovinos , Testículo/crecimiento & desarrollo , Aumento de Peso , Zeolitas
13.
J Anim Sci ; 78(1): 124-30, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10682812

RESUMEN

Research was conducted to evaluate the sensitivity of Bos indicus and Bos taurus cattle to a tall fescue ergopeptine alkaloid by assessing vital sign responses. Eight Polled Hereford and seven Red Brahman steers received bolus i.v. injections of ergotamine tartrate and saline vehicle in a simple cross-over design. Physiological traits measured 30 min and immediately before and 30, 60, and 90 min after treatment were respiration rate, rectal temperature, skin temperature at the tailhead and tail tip, systolic and diastolic blood pressure, and heart rate. Blood samples were collected immediately before and 105 min after treatments to determine plasma prolactin and cortisol concentrations. Steers were fed a fescue-free diet in drylot. Ambient temperature and relative humidity averaged 31 degrees C and 55%, respectively, during data collection. No breed x treatment x time interactions were apparent for vital signs. The treatment x time interaction was significant (P < .05) for blood pressure and skin temperature. Ergotamine increased (P < .01) blood pressure and decreased (P < .01) skin temperature. The breed x treatment x time interactions were significant for prolactin (P < .1) and cortisol (P < .01). Ergotamine decreased plasma (P < .01) prolactin and increased (P < .01) cortisol concentrations in both breeds, despite some breed variation. Across all traits, Brahman and Hereford steers responded similarly to acute ergotamine exposure, indicating that the breeds are alike in acute sensitivity to a systemically administered ergopeptine alkaloid associated with fescue toxicosis.


Asunto(s)
Bovinos/fisiología , Ergotamina/toxicidad , Animales , Presión Sanguínea/efectos de los fármacos , Regulación de la Temperatura Corporal , Fenómenos Fisiológicos Cardiovasculares/efectos de los fármacos , Bovinos/sangre , Bovinos/clasificación , Ergotamina/sangre , Frecuencia Cardíaca/efectos de los fármacos , Hidrocortisona/sangre , Prolactina/sangre
14.
Am J Vet Res ; 59(10): 1258-62, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9781458

RESUMEN

OBJECTIVES: To assess effects of vaccination against fescue toxicosis on weight gain, serum prolactin and cholesterol concentrations, and alkaline phosphatase (ALP) activity in mice fed an endophyte-infected (EI) or endophyte-free (EF) fescue diet. ANIMALS: 50 six-week-old male BALB/c mice. PROCEDURE: Mice were randomly allocated to the following 5 groups: 1, vaccinated intraperitoneally with a bovine serum albumin-ergotamine (EG) conjugate and fed an EI fescue diet; 2, orally vaccinated with cholera toxin (CT) subunit B-EG conjugate mixed with free CT and fed an EI fescue diet; 3, not vaccinated and fed an EI fescue diet; 4, passively vaccinated with monoclonal antibodies specific for ergovaline (EV) and fed an EI fescue diet; and 5, not vaccinated and fed an EF fescue diet. RESULTS: Antibodies against EG and EV were in serum of mice of groups 1 and 4, respectively. Secretory IgA and IgG coproantibodies against EG were induced in mice of group 2. Weight increased in groups 1 and 2 and tended to be increased in group 4 versus group 3. Prolactin concentration was similar in all groups; cholesterol concentration was decreased in groups 1, 3, and 4, compared with group 5. Compared with that in group 5, serum ALP activity decreased in groups 1 and 4 and was further decreased in group 1, compared with that in groups 2 and 3; it was negatively correlated with anti-EG titer. CONCLUSIONS AND CLINICAL RELEVANCE: Induction of anti-EG antibodies and administration of EV monoclonal antibodies tended to increase short-term weight gain in this murine model of fescue toxicosis. However, systemic IgG antibodies against EG or EV antibodies were not protective against decreases in serum ALP activity and cholesterol concentrations. Clinical significance of decreased ALP activity associated with vaccination is unknown, but represents a worsening of a response often associated with fescue toxicosis in cattle.


Asunto(s)
Ergotamina/toxicidad , Ergotaminas/inmunología , Plantas Tóxicas/toxicidad , Poaceae/toxicidad , Vacunación/veterinaria , Acremonium/patogenicidad , Fosfatasa Alcalina/sangre , Alimentación Animal/microbiología , Alimentación Animal/toxicidad , Animales , Anticuerpos Monoclonales/inmunología , Biomarcadores/sangre , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/prevención & control , Toxina del Cólera , Colesterol/sangre , Ergotaminas/análisis , Inmunización Pasiva/veterinaria , Inmunoglobulina G/biosíntesis , Masculino , Ratones , Ratones Endogámicos BALB C , Plantas Tóxicas/inmunología , Plantas Tóxicas/microbiología , Poaceae/inmunología , Poaceae/microbiología , Prolactina/sangre , Distribución Aleatoria , Albúmina Sérica Bovina , Aumento de Peso
15.
Clin Toxicol (Phila) ; 52(7): 674-7, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24978905

RESUMEN

BACKGROUND: Although uncommon, severe ergotism continues to occur. The purpose of this study is to describe causes and clinical effects of ergotism in recent years. METHODS: This is an observational case series with data obtained retrospectively from all patients with ergotism referred to Ramathibodi Poison Center in Bangkok, Thailand from January 2006 to August 2013. RESULT: Twelve cases of ergotism were identified. All cases involved ergotamine 1 mg/caffeine 100 mg combination tablets. Nine cases (75%) were precipitated by drug-drug interactions with CYP3A4 inhibitors. The other cases involved suicidal attempt (2 cases) and pediatric unsupervised ingestion (1 case). Ten patients (83%) had signs of peripheral vascular insufficiency. Five of these patients initially had factitiously low or unmeasurable blood pressure using non-invasive technique and had paradoxical increase following intravenous vasodilator administration. Two patients required partial foot amputations due to gangrene. Two patients, including a 15-month-old boy with an unsupervised ingestion, died. DISCUSSION: In this series, most cases of severe ergotism were associated with interaction with CYP3A4 inhibitors, which increase ergotamine bioavailability. Factitious low blood pressure in these cases was likely caused by severe vasospasm. CONCLUSION: Critical ergotism continues to occur in Thailand, most commonly associated with the drug-drug interactions.


Asunto(s)
Inhibidores del Citocromo P-450 CYP3A , Inhibidores Enzimáticos/efectos adversos , Ergotamina/toxicidad , Ergotismo/fisiopatología , Hipotensión/etiología , Vasoconstrictores/toxicidad , Adulto , Disponibilidad Biológica , Citocromo P-450 CYP3A/metabolismo , Interacciones Farmacológicas , Ergotamina/farmacocinética , Ergotismo/terapia , Resultado Fatal , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/etiología , Centros de Control de Intoxicaciones , Tailandia , Resultado del Tratamiento
16.
Rev. méd. Urug ; 34(2): 115-119, jun. 2018.
Artículo en Español | LILACS | ID: biblio-914559

RESUMEN

El ergotismo es un síndrome clínico poco frecuente pero potencialmente letal vinculado a la intoxicación aguda o crónica con el uso de alcaloides del ergot en el tratamiento de la migraña. Se caracteriza por un vasoespasmo severo generalizado que puede generar isquemia periférica o visceral y conducir a disfunción orgánica múltiple y muerte. Existen numerosos fármacos de metabolismo hepático que pueden alterar la metabolización de la ergotamina pudiendo alcanzar concentraciones tóxicas incluso a bajas dosis. Presentamos el caso de un paciente infectado con virus de la inmunodeficiencia humana bajo tratamiento antirretroviral que incluía inhibidores de la proteasa y que se había automedicado con ergotamina. El paciente presentó posteriormente sintomatología sensitivo motora deficitaria de miembros superiores e inferiores, acompañada de elementos de hipoperfusión distal severa. Se solicitó Doppler arterial que evidenció vasoespasmo de ejes arteriales de miembros. Se realizó diagnóstico de ergotismo secundario a la asociación de ergotamina - ritonavir, ingresando a cuidados intensivos. Se inició tratamiento en base a suspensión de ambos fármacos, vasodilatación arterial con nitroprusiato y antiagregación con ácido acetilsalicílico. En relación con este caso se presenta una revisión del mecanismo de toxicidad de la ergotamina, sus interacciones farmacológicas, así como diagnóstico y tratamiento disponibles para esta patología. (AU)


Ergotism is a rare but potentially lethal clinical syndrome linked to acute or chronic poisoning with the use of ergot alkaloids in the treatment of migraine. It is characterized by a severe generalized vasospasm that can generate peripheral or visceral ischemia and lead to multiple organ dysfunction and death. There are numerous drugs of hepatic metabolism that can alter the metabolism of ergotamine and can reach toxic concentrations even at low doses. We present the case of a patient infected with human immunodeficiency virus under antiretroviral treatment that included protease inhibitors and who had self-administered with ergotamine. The patient subsequently presented motor sensory deficit symptoms of upper and lower limbs, accompanied by elements of severe distal hypoperfusion. Arterial Doppler was requested, which showed vasospasm of the arterial axis of the limbs. A diagnosis of ergotism secondary to the ergotamine-ritonavir association was made, entering intensive care. Treatment was started based on suspension of both drugs, arterial vasodilatation with nitroprusside and antiaggregation with acetylsalicylic acid. In relation to this case, we present a review of the ergotamine toxicity mechanism, its pharmacological interactions, as well as the diagnosis and treatment available for this pathology. (AU)


O ergotismo é uma síndrome clínica pouco frequente, porém potencialmente letal vinculado à intoxicação aguda ou crônica pelo uso de alcalóides do Ergot no tratamento da enxaqueca. Caracteriza-se por um vaso espasmo severo generalizado que pode gerar isquemia periférica ou visceral e levar a disfunção orgânica múltipla e morte. Existem múltiplos fármacos de metabolismo hepático que podem alterar a metabolização da ergotamina podendo alcançar concentrações tóxicas inclusive em doses baixas. Apresentamos o caso de um paciente infectado com vírus da imunodeficiência humana recebendo tratamento antirretroviral que incluía inibidores da protease e que se automedicou com ergotamina. O paciente apresentou posteriormente sintomatologia sensitiva motora deficitária de membros superiores e inferiores, acompanhada de elementos de hipoperfusao distal severa. Solicitou-se Doppler arterial que mostrou vaso espasmo dos eixos arteriais de membros. Realizou-se diagnóstico de ergotismo secundário à associação ergotamina - ritonavir, e transferiu-se o paciente a cuidados intensivos. Iniciou-se tratamento com a suspensão de ambos os fármacos, vasodilatação arterial com nitroprussiato e antiagregaçao com ácido acetilsalicílico. Apresenta-se uma revisão do mecanismo de toxicidade da ergotamina, suas interações farmacológicas, seu diagnóstico e os tratamentos disponíveis para esta patologia. (AU)


Asunto(s)
Arterias/patología , Ergotismo , Ergotamina/efectos adversos , Ergotamina/toxicidad , Informes de Casos
17.
J Anim Sci ; 91(11): 5177-82, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23989880

RESUMEN

Diarrhea is caused by factors that alter absorption and secretion of water and ions across the intestinal epithelium and disrupt motility. Parasitic infection, stress, poor nutrition, and exposure to plant or fungal toxins predispose livestock to noninfectious diarrhea. This is more prevalent in sheep that graze pastures infected with wild-type endophytic fungus, suggesting the involvement of fungal alkaloids. These increase smooth muscle contraction: ergovaline/ergotamine (ergot alkaloid) activates serotonin (5-HT) receptors, and lolitrem B (indole diterpene) inhibits large-conductance Ca2+-activated K+ (BK) channels. Because of their separate mechanisms of action the objective of this study was to investigate whether they act synergistically to increase smooth muscle contraction. Effects of ergotamine (1 µM) and lolitrem B (0.1 µM) on the tension and frequency of spontaneous contractions were investigated in a longitudinal preparation of isolated distal colon. The compounds were dissolved in 0.1% dimethyl sulfoxide (DMSO) and applied separately or together for 1 h. Ergotamine increased contractile tension compared to the pretreatment control (P<0.01) and produced a short-lived increase in frequency (P<0.001). Lolitrem B increased contractile tension (P<0.05) but had no effect on frequency. When applied together, the contractile tension was greater than the sum of the compounds applied separately (P<0.05). The frequency of contractions was increased (P<0.05) but was not significantly different from that for ergotamine alone. The increased contractile tension when both compounds were applied together indicates that ergotamine and lolitrem B acted synergistically to increase smooth muscle contraction, suggesting that they would alter motility in vivo.


Asunto(s)
Colon/efectos de los fármacos , Ergotamina/toxicidad , Alcaloides Indólicos/toxicidad , Micotoxinas/toxicidad , Animales , Sinergismo Farmacológico , Ergotamina/administración & dosificación , Alcaloides Indólicos/administración & dosificación , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Micotoxinas/administración & dosificación , Ratas , Ratas Sprague-Dawley
18.
J Anim Sci ; 91(9): 4492-500, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23825335

RESUMEN

Pharmacologic profiling of serotonin (5HT) receptors of bovine lateral saphenous vein has shown that cattle grazing endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have altered responses to ergovaline, 5HT, 5HT2A, and 5HT7 agonists. To determine if 5HT receptor activity of tall fescue alkaloids is affected by grazing endophyte-free (EF), wild-type [Kentucky-31 (KY31)], novel endophyte AR542-infected (MAXQ), or novel endophyte AR584-infected (AR584) tall fescue, contractile responses of lateral saphenous veins biopsied from cattle grazing these different fescue-endophyte combinations were evaluated in presence or absence of antagonists for 5HT2A (ketanserin) or 5HT7 (SB-269970) receptors. Biopsies were conducted over 2 yr on 35 mixed-breed steers (361.5 ± 6.3 kg) grazing EF (n = 12), KY31 (n = 12), MAXQ (n = 6), or AR584 (n = 5) pasture treatments (3 ha) between 84 and 98 d (Yr 1) or 108 to 124 d (Yr 2). Segments (2 to 3 cm) of vein were surgically biopsied, sliced into 2- to 3-mm cross-sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O2/5% CO2; pH = 7.4; 37°C). Veins were exposed to increasing concentrations of 5HT, ergovaline, and ergovaline + 1 × 10(-5) M ketanserin or + 1 × 10(-6) M SB-269970 in Yr 1. In Yr 2, ergotamine and ergocornine were evaluated in presence or absence of 1 × 10(-5) M ketanserin. Contractile response data were normalized to a reference addition of 1 × 10(-4) M norepinephrine. In Yr 1, contractile response to 5HT and ergovaline were least (P < 0.05) in KY31 pastures and the presence of ketanserin greatly reduced (P < 0.05) the response to ergovaline in all pastures. However, presence of SB-269970 did not (P = 0.91) alter contractile response to ergovaline. In Yr 2, there was no difference in contractile response to ergotamine (P = 0.13) or ergocornine (P = 0.99) across pasture treatments, but ketanserin reduced (P < 0.05) the contractile response to both alkaloids. The 5HT2A receptor is involved in alkaloid-induced vascular contraction and alkaloid binding may be affected by exposure to different endophyte-fescue combinations.


Asunto(s)
Bovinos/metabolismo , Endófitos/fisiología , Alcaloides de Claviceps/toxicidad , Festuca/microbiología , Lolium/microbiología , Neotyphodium/fisiología , Vena Safena/metabolismo , Antagonistas de la Serotonina/farmacología , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Endófitos/química , Ergolinas/toxicidad , Ergotamina/toxicidad , Ergotaminas/toxicidad , Masculino , Neotyphodium/química , Distribución Aleatoria , Antagonistas del Receptor de Serotonina 5-HT2/farmacología
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