Endophytic fungal toxin effect on adrenergic receptors in lateral saphenous veins (cranial branch) of cattle grazing tall fescue.

The objective of this research was to characterize the adrenergic receptor response in veins of cattle that grazed tall fescue (Festuca arundinacea Schreb.), with (E+) and without (E-) fungal endophyte (Neotyphodium coenophialum) infection. Measurement of contractile response of lateral saphenous veins to selective adrenergic receptor agonists (alphal, phenylephrine; alpha2, BHT-920) revealed enhanced reactivity (greater contractile response) only for the alpha2 adrenergic receptor in E+ pastured cattle. This response was consistent over a 3-yr grazing period. Significant contractility differences in response to BHT-920 occurred at concentrations of 3x10(-6) M and greater. Early research has reasoned that the enhanced reactivity is due to endophyte toxin effect on intracellular signaling systems. The enhanced contractile effect would alter blood flow dynamics and contribute to clinical signs and pathologic change in animals. The alpha2-adrenergic receptor is also involved in the control of many metabolic reactions. Thus, for drug therapy to be successful in reversing the adverse effects of E+ tall fescue exposure in cattle, effects on the alpha2-adrenergic tissue receptors must be neutralized.

Evaluation of a dosing method for studying ergonovine effects in cattle.

We evaluated the feasibility of using miniosmotic pumps as a way to continuously treat cattle with a singular ergot alkaloid (ergonovine) of known content, thus mimicking the natural fescue toxicosis disease state, but allowing study of specific alkaloid effects. Dosing animals with increasing amounts of ergonovine via miniosomotic pumps, followed by daily acquisition of plasma samples for high-performance liquid chromatographic determination of the alkaloid, resulted in stepwise increases in plasma ergonovine concentration. However, despite the detectable blood concentration of ergonovine, calves did not have typical clinical signs of ergot alkaloid toxicosis. Similarly, serum prolactin concentration was unaffected by ergonovine in these cattle, implicating some other alkaloid of endophyte-infested fescue as causative of the usual prolactin-suppressive response. The results confirm use of this animal dosing method to study biological effects of singular purified alkaloids of known amount, without bioavailability concerns. Thus, this dosing method will facilitate studies to determine the harmful effects of individual alkaloids found in toxic tall fescue, and ultimately, to alleviate their costly effects in cattle, horses, and other species.

Vasoconstriction in bovine vasculature induced by the tall fescue alkaloid lysergamide.

Treatment of bovine lateral saphenous vein (cranial branch) and dorsal metatarsal artery with lysergamide (lysergic acid amide), an alkaloid in abundance in tall fescue, resulted in vasoconstriction similar to that previously shown for the ergot alkaloids ergonovine and ergotamine. Preincubation of tissues with lysergamide resulted in partial inhibition of the contractile response induced by the selective adrenergic agents phenylephrine and BHT-920 (P < .05), indicating partial agonist or antagonist activity of lysergamide at these receptors. Bovine vessels were strongly contracted by serotonin, and the response was markedly inhibited (P < .01) when tissues were preincubated with lysergamide. Studies with selective serotonergic agents indicated that lysergamide may have predilection for serotonin-2 receptors (5-HT2). Thus, lysergamide by itself has vasoconstrictor activity and acts as a partial agonist or antagonist at adrenergic and serotonergic receptors. Further studies are needed to establish the exact receptor effects of lysergamide. However, it is evident that this important alkaloid found in tall fescue infested with the endophytic fungus Acremonium coenophialum should be given consideration in studies designed to alleviate the fescue toxicosis syndrome in cattle.

Lactose intolerance in a calf.

Lactose intolerance was identified as the cause of bovine neonatal diarrhea. Glucose and xylose oral absorptions were normal whereas lactose absorption was reduced relative to normal calves. Lactase deficiency is common in people but rarely reported in animals. The treatment of whole milk with lactase alleviated the diarrhea.

Effects of phenothiazine and thiabendazole on bovine dorsal pedal vein contractility induced by ergonovine and serotonin; potential for alleviation of fescue toxicity.

Phenothiazine and thiabendazole were studied for their ability to antagonize venoconstriction induced by ergonovine, and the biogenic amine serotonin, in the isolated dorsal pedal vein of cattle. The two compounds are commercially available, approved for usage in cattle and have been reported to reverse some of the toxic effects associated with the intake of Acremonium coenophialum-infested fescue forage by cattle. Neither compound had any antagonistic activity against venoconstriction induced by ergonovine. However, thiabendazole did have some activity against venoconstriction induced by serotonin. Ergot alkaloids are known to cause venoconstriction through effects on biogenic amine receptors, including serotonergic receptors, and since thiabendazole has anti-serotonin activity, part of the reported beneficial effects of thiabendazole in alleviating fescue toxicity may be due to the anti-serotonin activity of the drug. Further work is needed to determine if phenothiazine and thiabendazole have any effect on other types of alkaloids that are present in A. coenophialum-infested fescue.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure.

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

Pulmonary hypertension in a group of dairy calves.

An episode of pulmonary arteritis and sclerosis in twenty 5- to 6-month-old dairy calves was investigated. Sixteen of the calves died acutely, without marked premonitory signs of disease. Four calves evaluated clinically had lethargy, pallor, weakness, tachycardia, tachypnea, and jugular venous distention. Cardiac catheterization performed in 3 of the calves revealed pulmonary hypertension; 1 of these calves survived. Necropsy findings in 19 calves included pale lungs and excess free fluid in the pleural and abdominal cavities. In addition, 13 of 19 calves had a dilated and thin-walled right ventricle; 4 of the calves had right-sided cardiac hypertrophy, and 2 had dilatation of the pulmonary artery. Microscopically, pulmonary arteritis and sclerosis of the small to medium-sized arteries were evident in all calves submitted for necropsy. A lung biopsy specimen from a surviving calf had similar lesions. Centrilobular hepatic necrosis was found in 17 of 19 calves. Investigation of the disease episode, including feed analysis for toxins and serologic and microbiological studies of clinically affected calves and clinically normal in-contact penmates, failed to reveal any associated risk factor. The pulmonary arterial changes in the calves were similar to lung lesions in rats fed monocrotaline.

A review of interstitial pneumonia in cattle.

Interstitial pneumonias comprise a significant proportion of cattle respiratory diseases. Known by different names, such as acute bovine pulmonary emphysema and edema (ABPE), fog fever, atypical interstitial pneumonia (AIP) and cow asthma, the condition seems to occur predominantly in late summer or fall. However, depending on the etiology, cases have occurred throughout the year. Interstitial pneumonia often begins with acute respiratory distress in animals that were clinically normal 12 hr earlier. Animals are observed breathing very rapid and shallow with their mouths open. If disturbed, death may occur rapidly from hypoxia. Causes of interstitial pneumonia are quite varied ranging from parasitic, viral and bacterial to toxic. Toxic agents constitute the most economically important cause of this condition in cattle. The primary toxin is the amino acid L-tryptophan in lush pasture grasses, a compound which is converted to 3-methylindole by rumen microorganisms. Other leading toxic causes of interstitial pneumonia are perilla mint and moldy sweet potatoes. Although treatments are mainly symptomatic and ineffective, preventive measures will reduce the occurrence of interstitial pneumonia. Prevention consists of denying animals exposure to know pneumotoxic agents, eliminating certain rumen microflora that break down the toxic compounds to reactive metabolites, and supplying ample good forage so that cattle will not as likely consume toxic plants.

Reactivity of dorsal pedal vein of cattle to selected alkaloids associated with Acremonium coenophialum-infected fescue grass.

We determined the vasoconstrictive effects of selected ergot alkaloids, and a sample containing loline and its derivative alkaloids, on the isolated dorsal pedal vein of cattle, as a model system to study one of the toxic effects that result from cattle ingesting fescue forage infected with the endophytic fungus Acremonium coenophilalum. The ergot compounds ergotamine, ergosine, and agroclavine constricted this peripheral vein of cattle, but much less so than did the alpha-adrenergic agonist norepinephrine, which supports the ergots acting as partial agonists for these receptors. However, the sample of loline and loline-derivative alkaloids did not affect the dorsal pedal vein when given at concentrations similar to those of the ergot compounds. Loline and loline-derivative alkaloid sample at high concentrations partially inhibited norepinephrine-elicited vascular contraction, an effect that appeared to be unrelated to alpha-adrenoceptor activity. Thus, in the dorsal pedal vein model in cattle, the ergopeptide alkaloids were more venoconstrictive than were loline and its derivative alkaloids.

Acute bovine pulmonary emphysema caused by the fungus Fusarium semitectum.

Acute bovine pulmonary emphysema (ABPE) is known to occur throughout the world. The documented causes include 3-methylindole, 4-ipomeanol and perilla ketone. Although 4-ipomeanol is a phytoallexin from Fusarium solani, this is the first reported incidence of toxicity involving Fusarium semitectum. This report describes the poisoning of cattle consuming Fusarium semitectum contaminated pink half-runner bean refuse.

Perilla ketone: a potent lung toxin from the mint plant, Perilla frutescens Britton.

Perilla ketone, from the essential oil of Perilla frutescens, is a potent pulmonary edemagenic agent for laboratory animals and livestock. This finding would account for reported effects of the plant on grazing cattle. The use of perilla in oriental foods and medicinal preparations suggests possible hazards to human health as well.