Locoweed (Oxytropis sericea)-induced lesions in mule deer (Odocoileius hemionus).

Locoweed poisoning has been reported in wildlife, but it is unknown whether mule deer (Odocoileius hemionus) are susceptible. In areas that are heavily infested with locoweed, deer and elk (Cervus elaphus nelsoni) have developed a spongiform encephalopathy, chronic wasting disease (CWD). Although these are distinct diseases, no good comparisons are available. The purpose of this study was to induce and describe chronic locoweed poisoning in deer and compare it with the lesions of CWD. Two groups of four mule deer were fed either a complete pelleted ration or a similar ration containing 15% locoweed (Oxytropis sericea). Poisoned deer lost weight and developed a scruffy, dull coat. They developed reluctance to move, and movement produced subtle intention tremors. Poisoned deer had extensive vacuolation of visceral tissues, which was most severe in the exocrine pancreas. Thyroid follicular epithelium, renal tubular epithelium, and macrophages in many tissues were mildly vacuolated. The exposed deer also had mild neuronal swelling and cytoplasmic vacuolation that was most obvious in Purkinje cells. Axonal swelling and dystrophy was found in many white tracts, but it was most severe in the cerebellar peduncles and the gracilis and cuneate fasciculi. These findings indicate that deer are susceptible to locoweed poisoning, but the lesions differ in severity and distribution from those of other species. The histologic changes of locoweed poisoning are distinct from those of CWD in deer; however, the clinical presentation of locoweed poisoning in deer is similar. Histologic and immunohistochemical studies are required for a definitive diagnosis.

Grazing of spotted locoweed (Astragalus lentiginosus) by cattle and horses in Arizona.

Spotted locoweed (Astragalus lentiginosus var. diphysus) is a toxic, perennial plant that may, if sufficient precipitation occurs, dominate the herbaceous vegetation of pinyon-juniper woodlands on the Colorado Plateau. Six cow/calf pairs and four horses grazed a 20-ha pasture with dense patches of locoweed in eastern Arizona during spring 1998. Locoweed density was 0.7 plants/m2 in the pasture. Locoweed averaged 30.4% NDF and 18.4% CP. Concentrations of the locoweed toxin, swainsonine, fluctuated from 1.25 to 2 mg/g in locoweed. Horses ate more (P < 0.01) bites of locoweed than did cows (15.4 and 5.1% of bites, respectively). Horses generally increased locoweed consumption over time since they ate approximately 5% of bites in the preflower stage compared with 25% of bites in the pod stage. Cattle consumed almost no locoweed (< 1% of bites) until the pod stage, when they increased consumption to 15% of bites. Horses were very avid (approximately 65 to 95% of bites) in selecting the small quantities (approximately 40 to 150 kg/ha) of available green grass, and it appeared that their propensity to eat scarce green forage influenced their locoweed consumption as well. Horses ate relatively little dry grass, even when it was abundant, whereas cattle ate large amounts of dry grass until green grasses became more abundant. Calves began eating locoweed on the same day as their dams and ate approximately 20% of their bites as locoweed. Serum concentrations of swainsonine were higher (P < 0.05) in horses than in cattle (433 vs. 170 ng/mL, respectively). Baseline swainsonine was zero in all animals, but swainsonine was rapidly increased to above 800 ng/mL in serum of horses as they ate locoweed. Horses exhibited depression after eating locoweed for about 2 wk; after 5 wk of exposure, horses became anorectic and behaviorally unstable. Although limited in scope, this study indicates that horses should not be exposed to spotted locoweed.

Evaluation of vaccination against methyllycaconitine toxicity in mice.

The purpose of this study was to determine whether larkspur toxins conjugated to protein carriers would promote active immunity in mice. Mice were injected with several larkspur toxin-protein conjugates or adjuvant alone to determine whether the resulting immunological response altered animal susceptibility to methyllycaconitine, the major toxic larkspur alkaloid. Although vaccinations increased the calculated lethal dose 50% (LD50) for intravenous methyllycaconitine toxicity, overlapping confidence intervals did not provide evidence of differences between the vaccinated and control groups. In the lycoctonine conjugate (LYC)-vaccinated group, mouse survival was related (P = 0.001) to serum titers for methyllycaconitine doses up to 4.5 mg/kg of body weight. When mice withlow antibody titers were removed from the vaccinated groups in which titer was related to survival, the recalculated LD50 estimates were 20% greater than the LD50 of the control group. However, the 95% confidence intervals of the recalculated LD50 groups overlapped with the control groups. Overall, these results suggest that vaccination altered methyllycaconitine toxicity in mice and that vaccination may be useful in decreasing the effects of larkspur toxins in animals. Additional studies are warranted to continue development of potential larkspur vaccines for livestock.

Neurologic disease in range goats associated with Oxytropis sericea (Locoweed) poisoning and water deprivation.

About 200/2500 Spanish goats foraging on mountain rangelands of western Montana developed neurologic disease with severe rear limb weakness, knuckling of the rear fetlocks, and a hopping gait. Sick goats were of all ages and in good flesh, though they often had dull, shaggy coats. Some mildly affected animals recovered after being moved to feed lots, but others progressed to recumbency, seizures and death. At necropsy both moribund and clinically affected animals had few gross lesions; 1 animal had contusions and puncture wounds on rear legs and perineum, suggestive of predator bites. Histologic lesions included mild vacuolation of neurons and visceral epithelial cells, mild diffuse cerebral edema with minimal neuronal pyknosis, and random, multifocal Wallarian degeneration of spinal cord axons. Affected animals had elevated serum sodium, potassium and chloride levels; other mineral analyses and serum biochemistries were within normal limits. Locoweed-induced depression and inhibition of neuromuscular function coupled with water deprivation due to predation pressure allowed development of neurologic disease and hypernatremia.

Comparison of cleft palate induction by Nicotiana glauca in goats and sheep.

The induction of cleft palate by Nicotiana glauca (wild tree tobacco) during the first trimester of pregnancy was compared between Spanish-type goats and crossbred western-type sheep. Cleft palate was induced in 100% of the embryonic/fetal goats when their pregnant mothers were gavaged with N. glauca plant material or with anabasine-rich extracts from the latter, during gestation days 32-41. Seventy-five percent of newborn goats had cleft palate after maternal dosing with N. glauca during gestation days 35-41, while no cleft palates were induced when dosing periods included days 36-40, 37-39, or day 38 only. The induced cleft palates were bilateral, involving the entire secondary palates with complete detachment of the vomer. Eleven percent of the newborn goats from does gavaged during gestation days 32-41 had extracranial abnormalities, most often contractures of the metacarpal joints. Most of these contractures resolved spontaneously by 4-6 weeks postpartum. One newborn kid also had an asymmetric skull due to apparent fetal positioning. No cleft palates were induced in lambs whose mothers were gavaged with N. glauca plant or anabasine-rich extracts during gestation days 34-41, 35-40, 35-41, 36-41, 35-51, or 37-50. Only one of five lambs born to three ewes gavaged with N. glauca plant material during gestation days 34-55 had a cleft palate, but all five of these lambs had moderate to severe contractures in the metacarpal joints. The slight to moderate contracture defects resolved spontaneously by 4-6 weeks postpartum, but the severe contractures resolved only partially. Embryonic/fetal death and resorption (determined by ultrasound) occurred in 25% of pregnant goats fed N. glauca compared to only 4% of pregnant sheep. Nicotiana glauca plant material contained the teratogenic alkaloid anabasine at 0.175% to 0.23%, dry weight, demonstrating that Spanish-type goats are susceptible to cleft palate induction by the natural toxin anabasine, while crossbred western-type sheep are resistant. However, clinical signs of toxicity were equally severe in goats and sheep, even though maternal alkaloid tolerance was generally lower in sheep. We postulate that an alkaloid-induced reduction in fetal movement during the period of normal palate closure is the cause of the cleft palate and multiple flexion contractures. Teratology 61:203-210, 2000. Published 2000 Wiley-Liss, Inc.

Pine needle abortion in cattle: metabolism of isocupressic acid.

The rumen and hepatic metabolism of the cattle abortifacient compound isocupressic acid (ICA) was examined in vitro and in vivo. ICA was incubated for 56 h in bovine rumen inoculum and was found to be converted to three compounds identified as imbricatoloic acid, a structurally uncharacterized isomer of imbricatoloic acid, and dihydroagathic acid. In preparations of liver homogenates, ICA was found to be oxidized to agathic acid. No differences in ICA metabolites were detected in comparing the cow, sheep, pig, goat, guinea pig, and rat livers; however, guinea pig and rat liver homogenates were less efficient in converting ICA to agathic acid. ICA had been administered to cows orally and by intravenous infusion and induced abortions after either method of treatment. After intravenous infusion, agathic acid was identified as the major metabolite together with minor amounts of dihydroagathic acid. After oral administration, dihydroagathic acid was identified as the major metabolite with minor amounts of agathic acid, imbricatoloic acid, and a structurally uncharacterized metabolite tentatively identified as tetrahydroagathic acid.

The fetal cleft palate: II. Scarless healing after in utero repair of a congenital model.

The role of fetal surgery in the treatment of non-life-threatening congenital anomalies remains a source of much debate. Before such undertakings can be justified, models must be established that closely resemble the respective human anomalies, and the feasibility and safety of these in utero procedures must be demonstrated. The authors recently described and characterized a congenital model of cleft palate in the goat. The present work demonstrates the methodology they developed to successfully repair these congenital cleft palates in utero, and it shows palatal healing and development after repair. A surgically created cleft model was developed for comparative purposes. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Six pregnant goats were gavaged twice daily during gestational days 32 to 41 (term, 145 days) with a plant slurry of Nicotiana glauca containing the piperidine alkaloid anabasine; the 12 fetuses had complete congenital clefts of the secondary palate. Repair of the congenital clefts was performed at 85 days of gestation using a modified von Langenbeck technique employing lateral relaxing incisions with elevation and midline approximation of full-thickness, bilateral, mucoperiosteal palatal flaps followed by single-layer closure. Six congenitally clefted fetuses underwent in utero repair, six remained as unrepaired controls. Twelve normal fetuses underwent surgical cleft creation by excision of a 20 x 3 mm full-thickness midline section of the secondary palate extending from the alveolus to the uvula, at 85 days of gestation. Six surgically clefted fetuses underwent concurrent repair of the cleft at that time; six clefted fetuses remained as unrepaired controls. At 2 weeks of age, no congenitally or surgically created clefts repaired in utero demonstrated gross or histologic evidence of scar formation. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. Cross-section through the mid-portion of the repaired congenitally clefted palates demonstrated reconstitution of a bilaminar palate, with distinct oral and nasal mucosal layers, after single-layer repair. In utero cleft palate repair is technically feasible and results in scarless healing of the mucoperiosteum and velum. The present work represents the first in utero repair of a congenital cleft palate model in any species. The use of a congenital cleft palate model that can be consistently reproduced with high predictability and little variation represents the ideal experimental situation. It provides an opportunity to manipulate specific variables, assess the influence of each change on the outcome and, subsequently, extrapolate such findings to the clinical arena with a greater degree of relevance.

Effects of locoweed (Oxytropis sericea) on reproduction in cows with a history of locoweed consumption.

Locoweed (Oxytropis sericea) was fed to 4 open cycling cows that had repeatedly consumed locoweed in previous grazing trails. They received locoweed at 20% of their diet for 30 d (0.68-0.76 mg swainsonine/kg/d). Locoweed induced an immediate rise in serum swainsonine (the locoweed toxin) and a concomitant drop in serum alpha-mannosidase activity in all cows accompanied by abnormal estrus behavior, increased estrous cycle lengths and failure to conceive. Serum progesterone (P4) profiles demonstrated that estrous cycles lengthened from an average of 19 d before locoweed feeding to an average of 34 d (range 24-43 d) while on locoweed. After locoweed feeding ceased, normal estrous cycles returned within an average of 14 d (range 7-25 d). Two of the 4 cows conceived on their first post-locoweed estrus at 7 and 25 d. The third cow bred twice at 13 and 31 d after lowoweed feeding stopped, and the fourth cow bred 3 times at 11, 31 and 52 d before conception occurred. Pregnancies in all 4 cows progressed normally to 7 mo gestation when locoweed was again fed at 20% of the diet for 40 d (gestation days 213 and 253) to 2/4 cows, 1 of which aborted 10 d after lowoweed feeding stopped (263 days gestation). The other cow fed lowoweed calved normally as did the 2 pregnancy control cows. Serum P4 and estradiol (E2) profiles during pregnancy appeared normal before, during and after locoweed feeding except in the cow that aborted, whose P4 declined and E2 increased prematurely. The general trend of serum prolactin was similar in locoweed-fed and control cows.

History of USDA poisonous plant research.

Research on poisonous plants was instituted by the United States Department of Agriculture (USDA) as a result of serious livestock poisoning by plants as the pioneers moved west in the mid-to-late 1800s and early 1900s. Historical records indicate the USDA began poisonous plant research in 1894 under the direction of Mr. V. K. Chestnut, a botanist (Table 1 briefly summarizes those who have directed poisonous plant research from the inception to the present). Mr. Chestnut's responsibility (1894-1904) was primarily administrative, although he did extensive field work in Washington and Montana. Temporary field stations were set up to study specific poisonous plant problems. These included field stations at Hugo and Woodland Park, Colorado, and Imperial, Nebraska (1905-1909), to study locoweed; Gunnison, Colorado (1910-1912), to primarily study larkspur; and Greycliff, Montana (1912-1915), to study the poisonous plants of the Yellowstone Valley. Dr. Rodney True replaced Mr. Chestnut in 1904 and in 1905 hired Dr. C. D. Marsh (1905-1930) to establish the temporary field stations listed above. In 1915 a permanent facility was established at Salina, Utah, under the direction of C. D. Marsh who remained in charge until 1930 when he retired; he was followed by A. B. Clawson until 1937 when Dr. Ward Huffman was placed in charge. Research on poisonous plants was located at the Salina Experiment Station until 1955 when the station was closed and the laboratory moved to the campus of Utah State Agricultural College at Logan, Utah, where it is currently located. Dr. Wayne Binns was hired as the director of the laboratory in 1954 and retired in 1972. In 1972 Dr. Lynn F. James, who joined the PRPL staff in July 1957, was appointed as Research Leader and presently directs the research at the Poisonous Plant Research Laboratory.