J. A. Stuedemann

Urinary Alkaloid Excretion as a Diagnostic Tool for Fescue Toxicosis in Cattle

Fescue toxicosis research studies have often included serum prolactin as a physiologic index of the disorder. Serum prolactin has not been used as a clinical measure of fescue toxicosis because of variation associated with sex and physiologic condition of the animal and climatic and seasonal factors. The primary excretory route of the alkaloids responsible for this toxicosis is the urine. Three pasture experiments were conducted to examine serum prolactin and urinary ergot alkaloid variability among steers continuously grazing endophyte-infected (E+) or endophyte-free (E-) tall fescue and among steers that were switched from one pasture form to the other. A fourth grazing experiment was used to examine how to best to manage the steers prior to sampling for urinary ergot alkaloid excretion. Coefficients of variability for urinary alkaloid excretion were consistently lower (46–65%) than serum prolactin (64–142%). Urinary alkaloid excretion patterns changed within 12 hours following switching steers from E+ to E- pasture or visa versa, but serum prolactin was recalcitrant to change. Because it is less variable and more dynamic than serum prolactin, urinary alkaloid excretion can be used for health assessment of steers grazing E+ and E- pastures. Regression analysis established a quadratic relationship between alkaloid excretion and average daily weight gain, with a regression coefficient of 0.86. Urinary alkaloid analysis was useful in determining whether cattle were consuming toxic tall fescue.

Immunosuppression in Cattle with Fescue Toxicosis

Anecdotal observations suggest that cattle entering feed lots after grazing endophyte-infected tall fescue have increased morbidity and mortality (Purdy et al.,1989). The morbidity and mortality has been interpreted as resulting from reduced immune functions in animals with fescue toxicosis. Rats fed endophyte-infected seed diets had lower serum antibody titers to sheep red blood cells than rats fed endophyte-free seed diets. In addition, spleen cells from rats on the endophyte-infected seed diets bad reduced mitogen response (Dew et al.., 1990). A consistent physiologic change associated with fescue toxicosis is hypoprolactinemia (Thompson et al., 1987). There is an increasing body of literature that indicates that prolactin functions as a co-factor in the regulation of the immune response (Reber,1993). Based on these observations the hypothesis was developed that cattle with fescue toxicosis would have decreased ability to produce antibodies to a protein antigen.

In vitro and in vivo release of metoclopramide from a subdermal diffusion matrix with potential in preventing fescue toxicosis in cattle

An auricular implant (0.5 × 3.7 cm) containing metoclopramide was developed for use in cattle as a therapeutic aid in antagonizing the harmful effects associated with grazing of endophyte-infected fescue pastures. The implant matrix was prepared from the biodegradable polymer, polyhydroxybutyrate and its copolymer polyhydroxyvalerate using compression-melt and solvent-evaporation compression techniques. Fabrication variables evaluated in in vitro dissolution studies included concentration of copolymer, drug payload, salt form vs. free base form of drug, and degree of compression. The optimal system consisted of a matrix containing 24% copolymer with a 50% drug payload that was prepared with the compression-melt technique. An in vivo study in cattle was conducted to assess biocompatibility and verify the dissolution rate in the whole animal. No adverse reactions occurred. The metoclopramide implant had a dissolution rate of 12 mg/day and was vascularized by the surrounding connective tissue. The matrix sham had no observable vascularization. An additional study used twelve pairs (one implanted, the other control) of steers placed on four different endophyte/nitrogen grazing treatments. The total ergot content (0.2–2.2 μg/g) of the twelve fescue paddocks was measured by HPLC, and fraction of Acremonium endophyte infection (23–67%) was determined by aniline stain. The implant resulted in an improvement in suppressed tail temperature (P < 0.01) among all endophyte/nitrogen treatments, and cholesterol (P < 0.01) among the high endophyte/nitrogen treatments.

Anti-Inflammatory Effects of Ergotamine in Steers (44562)

The objective of this experiment was to investigate whether the ergot alkaloid, ergotamine (ET), an alkaloid used to model fescue toxicosis in cattle, modifies the response of cattle to endotoxin (LPS) challenge. Steers (n = 16) were divided into the following treatment groups: control (C), ergotamine (ET), endotoxin (LPS), and ET + LPS. ET and ET + LPS groups received a single bolus intravenous injection of ET (40 μg · kg · body wt-1), whereas C and LPS steers received a single bolus injection of sterile vehicle. Thirty minutes after ET/vehicle administration, a single bolus intravenous injection of LPS (0.2 μg · kg · body wt-1) was given. Blood was collected at various time points for 48 hr post. Endotoxin increased rectal temperature (RT) and the circulating levels of tumor necrosis factor-α (TNF-α), cortisol, haptoglobin (Hp), thromboxane B2 (TXB2). The circulating Hp, TNF-α, and TXB2 increases were blunted by pretreatment with ET compared with ET + LPS. Ergotamine by itself increased circulating cortisol and RT, whereas it decreased serum prolactin (PRL). Therefore, whereas administration of LPS at 0.2 μg/kg to steers resulted in an expected response, the combination of ET + LPS attenuated major effects of LPS alone. Thus, acute administration of ET appeared to be anti-inflammatory as it decreased the Inflammatory response to LPS, an effect likely driven at least in part by the ET-caused cortisol increase.