Rumen and Serum Metabolomes in Response to Endophyte-Infected Tall Fescue Seed and Isoflavone Supplementation in Beef Steers.

Fescue toxicosis impacts beef cattle production via reductions in weight gain and muscle development. Isoflavone supplementation has displayed potential for mitigating these effects. The objective of the current study was to evaluate isoflavone supplementation with fescue seed consumption on rumen and serum metabolomes. Angus steers (n = 36) were allocated randomly in a 2 × 2 factorial arrangement of treatments including endophyte-infected (E+) or endophyte-free (E-) tall fescue seed, with (P+) or without (P-) isoflavones. Steers were provided a basal diet with fescue seed for 21 days, while isoflavones were orally administered daily. Following the trial, blood and rumen fluid were collected for metabolite analysis. Metabolites were extracted and then analyzed by UPLC-MS. The MAVEN program was implemented to identify metabolites for MetaboAnalyst 4.0 and SAS 9.4 statistical analysis. Seven differentially abundant metabolites were identified in serum by isoflavone treatment, and eleven metabolites in the rumen due to seed type (p < 0.05). Pathways affected by treatments were related to amino acid and nucleic acid metabolism in both rumen fluid and serum (p < 0.05). Therefore, metabolism was altered by fescue seed in the rumen; however, isoflavones altered metabolism systemically to potentially mitigate detrimental effects of seed and improve animal performance.

Headache in an HIV-Positive Patient: Dangerous Interaction.

Ergotism is an ischaemic complication due to vasoconstriction throughout the body due to ingestion of ergotamine. A 34-year-old Hispanic man with HIV infection treated with saquinavir, ritonavir and abacavir/lamivudine presented to the emergency department complaining of left foot pain 1 week prior to admission. The affected extremity was cold with absence of pedal and tibial pulses. Arterial Doppler revealed absent arterial flow from the popliteal artery later confirmed by arteriography. Medication reconciliation revealed a recent prescription for migraine headache containing ergotamine. Drug was discontinued and the patient was started on cilostazol, enoxaparin and nitroglycerin patches on the affected limb. Complete resolution of symptoms and arteriography findings occurred 2 days after therapy began.

Ergotism unresponsive to multiple therapeutic modalities, including sodium nitroprusside, resulting in limb loss.

Unlike epidemics in past centuries, patients suffering from peripheral vascular ischemia related to ergotism now rarely lose a limb because of vasodilator therapies. We report a patient with ischemia from ergotamine tartrate who failed to recover with medical therapy, resulting in limb amputation.

Ergotismo: revisión de la bibliografíay presentación de casos / Ergotism: review of the literature and some case reports

Introducción. Aunque el ergotismo o fuego de san Antonio tiene múltiples presentaciones, la más común en la actualidad es la isquemia periférica secundaria a vasoespasmo, que ocurre entre un 0,001-0,002 por ciento de aquellos pacientes en tratamiento con alcaloides ergóticos. Objetivo. Realizar un estudio retrospectivo de la isquemia ergótica en nuestro medio, y, dado que no existe una pauta de actuación estandarizada a seguir, basándonos en nuestra experiencia personal en el Hospital de la Santa Creu i Sant Pau (HSCSP) y en la diversa bibliografía consultada, plantear una terapéutica basada principalmente en la retirada de ergóticos y en la infusión endovenosa de prostaglandinas, con cretamente alprostadil(PGE1)-a-ciclo-dextrano (Sugiran,), por su gran efecto vasodilatador arterial y su acción antiagregante plaquetaria. Pacientes y métodos. Presentamos la serie de nuestro grupo de trabajo en los últimos cinco años, que incluye cuatro casos de isquemia arterial (dos hombres y dos mujeres) con afectación de las extremidades inferiores en tres casos y las superiores en uno. Todos los casos se trataron con supresión de ergóticos, infusión endovenosa de alprostadil (PGE1)-a-ciclo-dextrano, más fármacos coadyuvantes en algunos casos (heparinas, antiagregantes y hemorreológicos). Resultados. Los pacientes presentaron una franca mejoría tras la retirada de los ergóticos; desapareció la amenaza para la extremidad y el dolor en reposo entre 24 y 72 h tras el inicio de la infusión de prostaglandinas. El cuadro clínico mejoró en pocos días, y se recuperaron los pulsos distales en la totalidad de los casos. Conclusiones. Consideramos el uso de alprostadil(PGE1)-a-ciclo-dextrano como una opción terapéutica válida en el tratamiento de la isquemia de etiología ergótica (AU)

Systemic relaxin in pregnant pony mares grazed on endophyte-infected fescue: effects of fluphenazine treatment.

Tall fescue is one of the most widely grown forage grasses for horses in the United States. However, it is frequently infected with the endophyte Neotyphodium coenophialum which produces ergot alkaloids that cause severe adverse effects in the pregnant mare. The objectives of this study were to determine the effects of fescue toxicosis and fluphenazine on circulating relaxin in pregnant pony mares and evaluate the usefulness of relaxin as a monitor of treatment efficacy. Twelve mares were maintained on endophyte-infected tall fescue pasture. Group TRT (n = 6), received 25 mg of fluphenazine decanoate (i.m.) on Day 320 of gestation while Group UTRT served as untreated controls. Daily blood samples were collected from Day 300 of gestation until Day 3 post partum and analyzed for plasma relaxin concentrations using a homologous equine radioimmunoassay. Mean gestation lengths were 330 +/- 0.7 and 336.5 +/- 3.2 days for TRT and UTRT mares, respectively (P = 0.07). Mean plasma relaxin concentrations in both groups of mares during the week before treatment (Day 313 to 319) were not different (UTRT, 53.4 +/- 11.3 ng/mL; TRT, 61.4 +/- 9.3 ng/mL). In the week after treatment (Day 320 to 326), mean plasma relaxin tended to be higher (P = 0.1) in TRT mares (66.7 +/- 6.2 ng/mL) when compared with UTRT mares (49.6 +/- 6.6 ng/mL), representing a 17.1 ng/mL difference in circulating relaxin between the two groups. Systemic relaxin during the last week before delivery (days relative to parturition) for UTRT and TRT mares was 45.7 +/- 6.7 and 64.7 +/- 6.4 ng/mL (P = 0.06), respectively. At Day -8 and Day -5 relative to parturition, systemic relaxin in TRT mares was significantly higher (P < 0.05) than in UTRT mares. Three of the six UTRT mares and one TRT mare showed clinical symptoms of fescue toxicosis. In the week before delivery, circulating relaxin in mares with problematic pregnancies (39.9 +/- 7.8 ng/mL) was significantly lower than concentrations measured in mares with normal pregnancies (63.4 +/- 5.4 ng/mL; P = 0.03). Clinical observations suggest that a one-time injection with fluphenazine improved pregnancy outcome by reducing the adverse effects of fescue toxicosis concomitant with a stabilization of plasma relaxin concentrations. These data support the hypothesis that systemic relaxin may be a useful biochemical means of monitoring placental function and treatment efficacy in the mare.

Vitamin E influence on selected parameters in rats after ochratoxin A intoxication.

The aim of the research was to evaluate vitamin E influence on ochratoxin A (OTA) toxicity based on analysis of selected parameters of white and red cell system in rats. The animals were divided into groups: I--control, II--treated with OTA, III--treated with OTA and vitamin E. In group II a significant decrease in the values of hematocrit, hemoglobin level, red and white cell counts was observed. In group III an average hematocrit, hemoglobin level were significantly lower than in control group, nevertheless they were higher than in group II.

Eficacia de la PGE1 en el tratamiento de la intoxicación crónica por ergotamina / Effectiveness of PGE1 for the treatment of chronic poisoning byergotamine

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Injection of a dopamine antagonist into Holstein steers to relieve symptoms of fescue toxicosis.

Two experiments were conducted to determine whether administering a dopamine antagonist to steers fed endophyte-infected (E+) tall fescue would increase serum prolactin (PRL) and reduce rectal temperature. Steers in both experiments were housed in environmentally controlled chambers (32 degrees C; 50% relative humidity). In Exp. 1, 10 steers were allotted randomly to receive s.c. injections of either 0, .006, .03, or .06 mg of Ro 24-0409 (dopamine antagonist)/kg BW. The experiment was designed in four phases: endophyte-free seed (E-) without antagonist (d -11 to 0); E- with antagonist (d 0 to 7); E+ with antagonist (d 7 to 28); E+ without antagonist (d 28 to 38). In Exp. 2, 22 Holstein steers were allotted randomly to the same treatments and design, except three steers were maintained on E- without antagonist. Steers were fed individually with intakes measured daily. In Exp. 1, feed intake and rectal temperature were not improved (P > .05) by antagonist injection. In Exp. 2, antagonist injections increased (P < .05) PRL. Ingestion of E+ decreased (P < .05) feed intake and serum PRL. Antagonist injection decreased (P < .05) rectal temperature and increased (P < .05) serum PRL.

[Acute ischemia of an arm as an unusual manifestation of ergotism]. / Akute Ischämie eines Armes als ungewöhnlicher Ausdruck eines Ergotismus.

A 27-year-old woman developed acute pain, pallor and feeling of cold in her left arm. She had been a smoker of 15-20 cigarettes daily since the age of 15 years, but had not previously had any serious illness. In addition to contraceptives she had had been taking one to several suppositories containing caffeine and ergotamine tartrate (2 mg) daily against migraine. Angiological examination 5 days after onset of symptoms discovered a weak brachial pulse low in the left upper arm, while ulnar and radial pulses were absent. All other pulses were normally palpable. Colour duplex sonography demonstrated occlusion of the brachial artery which angiographically was due to a 5 cm severe narrowing without thrombus, blood flowing distally via collaterals. No improvement was achieved by local injection of 100,000 IU urokinase, 0.5 mg nitroglycerin, 20 mg tolazoline and a 3-hour infusion of alprostadil. On infusion of 560 ml hydroxyethylstarch over 8 hours, 400 mg naftidrofuryl, therapeutic doses of heparin and abstinence from ergotamine (since admission) the vessel diameter increased by 50% within 23 hours and after a further 24 hours to almost 100% of the comparable arterial segment of the right arm while merely on heparin infusion.

Successful limb salvage with prostaglandin infusion: a review of ergotamine toxicity.

OBJECTIVE: A case of severe acute peripheral arterial insufficiency secondary to ergotamine toxicity treated successfully with intravenously administered prostaglandin is presented to highlight the features of this condition and to demonstrate the efficacy of treatment with prostaglandin infusion. CLINICAL FEATURES: A 35-year-old unemployed Caucasian woman with a background of polypharmacy abuse and recurrent migraines presented to St Vincent's Hospital Emergency Department with limb-threatening ischaemia of both legs secondary to chronic ergotamine overuse. INTERVENTION AND OUTCOME: A prostaglandin infusion was started and a dramatic and rapid improvement of her peripheral circulation occurred within six hours. CONCLUSION: Ergotamine toxicity is an uncommon but well documented cause of peripheral vascular insufficiency that should be recognised and treated aggressively because its sequelae can be disastrous. Intravenously administered prostaglandin proved to be successful in this case and is a logical choice as first-line therapy for ergotamine toxicity.

[Extremity-threatening ischemia in ergotism. Successful treatment with the intra-arterial administration of nifedipine]. / Extremitätenbedrohende Ischämie bei Ergotismus. Erfolgreiche Behandlung durch intraarterielle Gabe von Nifedipin.

A 39-year-old woman suffering from migraine took two suppositories of an ergotamine-containing proprietary drug (Cafergot, containing 2 mg ergotamine tartrate) for the first time again after an abstinence of two years. Twenty-four hours later she developed symptoms of decreased peripheral blood flow in all four limbs. Walking distance without pain was reduced to 100 m, but the severest changes affected the right arm, with livid discolorations and complete immobility 16 hours after the onset of symptoms. Despite administration of morphine derivatives the pain progressively increased. Angiography demonstrated spastic narrowing of all arm arteries below the axillary artery. No vessels were visualized below the lower-arm bifurcation. Thereupon 4 mg nifedipine were injected through the angio-catheter within 30 min (five individual doses of 0.8 mg each). This was followed by intravenous infusion of 0.5 mg/h. The pain immediately decreased and the livid discoloration as well as impaired arm movement improved. A residual deficit, incomplete lesion of the median nerve, persisted but gradually regressed during the following two months.

Severe iatrogenic ergotism: incidence and clinical importance.

Ergot's derivatives are widely used to treat and prevent migraine and, associated with heparin, for the prevention of deep vein thrombosis. During a five-year period, 7 patients have been admitted in our hospital for severe vasospasm of one or several extremities due to ergot's derivatives. All patients presented with acute severe ischemia of the lower limb requiring iv infusion of vasodilator drugs. Ergotamine tartrate was the responsible drug in four patients and dihydroergotamine(DHE)-heparin in three patients. Intravenous administration of sodium nitroprusside (n = 6) relieved vasospasm in all but one of the patients within hours to days and no amputation was required. Ankle or great toe to arm systolic pressure index was normalized in the majority of the patients after treatment. A sympathectomy was performed in two patients which did not improve the clinical course. Distal necrosis developed in two patients (DHE-heparin). It is concluded that incidence of severe ergotism is less than 0.5/100,000/year in Geneva. This contrasts with the high prevalence (15%) of subclinical ergotism reported by others. No amputation was required in this series in spite of severe and prolonged vasospasms. Subclinical ergotism most probably precedes for weeks the onset of severe vasospasm, which calls for close monitoring of patients taking ergot's derivatives.

[Ergotamine induced ischemia]. / Ergotaminindusert ischemi.

Drugs containing ergotamine are commonly used in the treatment of migraine. Hypersensitivity to these drugs may be triggered off even with intake of recommended doses, inducing peripheral ischemia. Contributing factors to ergotism are concurrent fever, liver disease and drugs such as erythromycin or propranolol. We present a case history and different methods of treatment.

[Diagnosis and therapy of ergotism following the use of heparin-DHE in thrombosis prevention]. / Diagnostik und Therapie des Ergotismus nach Heparin-DHE-Thromboseprophylaxe.

Vasospastic complications have been reported in five patients following the use of heparin-dihydroergotamine for thrombo-embolic prophylaxis. The most important diagnostic procedure is angiography, which shows characteristic findings. Intraarterial prostaglandin is a promising form of treatment. Experience with two patients is reported.