Biomedical subjects

D R Gardner

Publications and source records attributed to D R Gardner.

At least 37 records · Page 2Linked to original sources

PubMed2000

Development of enzyme-linked immunosorbent assays for toxic larkspur (Delphinium spp.) alkaloids.

Larkspur (Delphinium spp.) poisons thousands of cattle on western rangelands each year. Because poisoning does not cause specific lesions, and poisoned animals are rarely found before they die, definitively identifying poisoned animals is difficult. Additionally, toxin concentrations in larkspur plants vary with environment, plant, and location. Rapid, sensitive, and specific diagnostic techniques are needed to identify poisoned animals and to determine when and what plants are likely to poison livestock. In this study, three competitive inhibition enzyme-linked immunosorbent assays (CI-ELISA) for toxic larkspur alkaloids were developed. One assay is class-specific toward the N-(methylsuccinimido)anthranoyllycoctonine (MSAL) alkaloids, and two assays are specific for individual alkaloids. The assay with the lowest limit of detection had an I(50) of 191 pg with a limit of detection of 30.5 pg for methyllycaconitine. Spike and recovery studies using bovine blood and brain tissue ranged from 52 to 89%. These findings suggest that with additional development these techniques are likely to be excellent tools for diagnosing poisoned animals and identifying highly toxic plants.

Alkaloids↗

PubMed2000

Three new toxic norditerpenoid alkaloids from the low larkspur Delphinium nuttallianum.

Three new N-(methylsuccinimido)anthranoyllycoctonine norditerpenoids, given the names bearline (1), 14-acetylbearline (2), and 16-deacetylgeyerline (3), were isolated from the extract of the low larkspur Delphinium nuttallianum. The structures of the individual alkaloids were determined by (1)H and (13)C NMR spectroscopy and HRMS. These alkaloids are structurally related to the neurotoxic alkaloid methyllycaconitine (4) and may be important in establishing the toxicity of low larkspurs to cattle. A mouse bioassay was used to measure the LD(50) values for two of the new alkaloids (1 and 2), as sufficient quantities of 3 were not available for toxicity testing. A structurally related alkaloid, geyerline (7), was isolated from D. geyeri in sufficient quantities for toxicity testing. The toxicities of 1, 2, and 7 were found to be comparable to that of 4, with calculated LD(50) values in mice of 5.7, 3.3, and 6.2 mg/kg, respectively.

Aconitine↗

PubMed2000

GC/MS/MS detection of pyrrolic metabolites in animals poisoned with the pyrrolizidine alkaloid riddelliine.

Pyrrolic metabolites from pyrrolizidine alkaloids (PAs) were detected in liver and dried blood samples using a gas chromatography/tandem mass spectrometry (GC/MS/MS) selected product-ion-monitoring method. A calibration curve was constructed using a protein-metabolite conjugate spiked into dried bovine blood. These spiked samples served as a model for tissues from animals poisoned by the toxic metabolite of PAs. Tissue samples from pigs fed various amounts of the PA alkaloid riddelliine (from Senecio riddellii) were analyzed for pyrrolic metabolites, and the results were applied to the calibration curve to provide a measure of the degree of PA poisoning. Pyrrolic metabolites were detected in liver and blood samples of all poisoned animals at levels between 2 and 64 ppm. Although differences in metabolite levels could be discerned under the reported experimental conditions, the amount detected did not correlate with the dose of riddelliine given; and livers fixed with formalin gave greatly reduced recovery than those same livers either frozen or freeze dried.

Animals↗

PubMed1999

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.

Abortifacient Agents↗

PubMed1999

Analysis of toxic norditerpenoid alkaloids in Delphinium species by electrospray, atmospheric pressure chemical ionization, and sequential tandem mass spectrometry.

A rapid electrospray mass spectrometry method was developed for screening larkspur (Delphinium spp.) plant material for toxic norditerpenoid alkaloids. The method was calibrated using two standard alkaloids, methyllycaconitine (1) and deltaline (2), with a recovery of 92% from spiked samples and relative standard deviations of 6.0% and 8.1% for the two alkaloids, respectively. Thirty-three samples of plains larkspur, Delphinium geyeri, were analyzed. Methyllycaconitine (1) concentration was 0.27% +/- 0.08% during a 1-month period in 1997 establishing the relative risk of poisoning from the plant to be low. The method was also applied to the trace analysis (<1 ppm) of 1 in serum samples from sheep dosed different levels of the alkaloid. Electrospray ionization combined with sequential tandem mass spectrometry and HPLC coupled to atmospheric pressure chemical ionization (APCI) mass spectrometry were used to detect and tentatively identify three new norditerpenoid alkaloids from Delphinium nuttallianum [bearline (6), 14-acetylbearline (7), 16-deacetylgeyerline (8)]. The tentative structure of the new alkaloids was predicted from the tandem mass spectra fragmentation patterns and assigning the substitution pattern for methoxy and acetyl groups at the C-14 and C-16 carbons.

Alkaloids↗

PubMed1999

FMRFamide-activated Ca2+ channels in Lymnaea heart cells are modulated by "SEEPLY," a neuropeptide encoded on the same gene.

The cell-attached, patch-clamp technique was used to investigate the modulatory role of the neuropeptide SEQPDVDDYLRDVVLQSEEPLY ("SEEPLY") on FMRFamide-activated Ca2+ channels in isolated Lymnaea heart ventricular cells. Both SEEPLY and FMRFamide are encoded on the same neuropeptide gene and are coexpressed in a pair of excitatory motor neurons that innervate the heart. FMRFamide applied alone was capable of significantly increasing the P(open) time of a Ca2+ channel in isolated heart muscle cells. However, SEEPLY applied alone did not significantly alter the basal level of Ca2+ channel activity in the same cells. Repeated applications of FMRFamide (15 s every min) resulted in a progressive reduction in the number of Ca2+ channel openings and the overall P(open) time of the channel. The fifth successive 15-s application of FMRFamide failed to cause the Ca2+ channels to open in the majority of cells tested. When FMRFamide and SEEPLY were repeatedly applied together (2-min applications every 4 min) the FMRFamide-activated Ca2+ channels continued to respond after the fifth application of the two peptides. Indeed channel activity was seen to continue after repeated 2-min applications of FMRFamide and SEEPLY for as long as the patch lasted (</=60 min). As well as preventing the loss of response to FMRFamide, SEEPLY was also capable of both up- and down-regulating the response of the Ca2+ channel to FMRFamide. The direction of the response depended on the P(open) time of the channel before the application of SEEPLY. When the P(open) time for the FMRFamide-activated channel was initially 0.004 +/- 0.002 (means +/- SE), subsequent perfusion with a mixture of FMRFamide and SEEPLY produced a statistically significant increase in Ca2+ channel activity (13 cells). In two cells where no channel activity was observed in response to an initial application of FMRFamide, superfusing the heart cells with a mixture of FMRFamide and SEEPLY induced openings of the Ca2+ channel. When the P(open) time of FMRFamide-induced Ca2+ channel openings was 0.058 +/- 0.017 the subsequent application of a mixture of SEEPLY and FMRFamide caused a statistically significant decrease in Ca2+ channel activity (8 cells). As up- and down-regulation of FMRFamide-activated Ca2+ channel openings by SEEPLY were observed in the same cells (8 cells), this suggested that corelease of the two peptides might act together to regulate the level of Ca2+ channel activity within a defined range.

Amino Acid Sequence↗

PubMed1999

Dose response of sheep poisoned with locoweed (Oxytropis sericea).

Locoweed poisoning occurs when livestock consume swainsonine-containing Astragalus and Oxytropis species over several weeks. Although the clinical and histologic changes of poisoning have been described, the dose or duration of swainsonine ingestion that results in significant or irreversible damage is not known. The purpose of this research was to document the swainsonine doses that produce clinical intoxication and histologic lesions. Twenty-one mixed-breed wethers were dosed by gavage with ground Oxytropis sericea to obtain swainsonine doses of 0.0, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.0 mg/kg/day for 30 days. Sheep receiving > or = 0.2 mg/kg gained less weight than controls. After 16 days, animals receiving > or = 0.4 mg/kg were depressed, reluctant to move, and did not eat their feed rations. All treatment groups had serum biochemical changes, including depressed alpha-mannosidase, increased aspartate aminotransferase and alkaline phosphatase, as well as sporadic changes in lactate dehydrogenase, sodium, chloride, magnesium, albumin, and osmolarity. Typical locoweed-induced cellular vacuolation was seen in the following tissues and swainsonine doses: exocrine pancreas at > or = 0.05 mg/kg; proximal convoluted renal and thyroid follicular epithelium at > or = 0.1 mg/kg; Purkinje's cells, Kupffer's cells, splenic and lymph node macrophages, and transitional epithelium of the urinary bladder at > or = 0.2 mg/kg; neurons of the basal ganglia, mesencephalon, and metencephalon at > or = 0.4 mg/kg; and cerebellar neurons and glia at > or = 0.8 mg/kg. Histologic lesions were generally found when tissue swainsonine concentrations were approximately 150 ng/g. Both the clinical and histologic lesions, especially cerebellar lesions are suggestive of neurologic dysfunction even at low daily swainsonine doses of 0.2 mg/kg, suggesting that prolonged locoweed exposure, even at low doses, results in significant production losses as well as histologic and functional damage.

Animals↗

PubMed1999

Ponderosa pine and broom snakeweed: poisonous plants that affect livestock.

Ponderosa pine (Pinus ponderosa) and the snakeweeds (Gutierrezia sarothrae and G. microcephala) are two groups of range plants that are poisonous to livestock. Ponderosa pine causes late-term abortions in cattle, and the snakeweeds are toxic and also cause abortions in cattle, sheep, and goats. Research is underway at the USDA-ARS-Poisonous Plants Research Laboratory to better understand livestock poisonings caused by grazing ponderosa pine needles and the snakeweeds and to provide methods of reducing losses to the livestock and supporting industries. This review includes the history of the problem, a brief description of the signs of poisoning, the research, to identify the chemical toxins, and current management practices on prevention of poisonings.

Abietanes↗

PubMed1999

The pathogenesis and toxicokinetics of locoweed (Astragalus and Oxytropis spp.) poisoning in livestock.

Locoweed poisoning is a chronic disease that develops in livestock grazing for several weeks on certain Astragalus and Oxytropis spp. that contain the locoweed toxin, swainsonine. The purpose of this review is to present recent research on swainsonine toxicokinetics and locoweed-induced clinical and histologic lesions. Swainsonine inhibits cellular mannosidases resulting in lysosomal storage disease similar to genetic mannosidosis. Diagnosis of clinical poisoning is generally made by documenting exposure, identifying the neurologic signs, and analyzing serum for alpha-mannosidase activity and swainsonine. All tissues of poisoned animals contained swainsonine, and the clearance rates from most tissues was about 20 hours (T1/2 half life). The liver and kidney had longer rate of about 60 hours (T1/2). This suggests that poisoned animals should be allowed a 28-day withdrawal to insure complete swainsonine clearance. Poisoning results in vacuolation of most tissues that is most obvious in neurons and epithelial cells. Most of these histologic lesions resolved shortly after poisoning is discontinued; however, some neurologic changes are irreversible and permanent.

Animal Feed↗

PubMed1999

Larkspur (Delphinium spp.) poisoning in livestock.

Larkspurs (Delphinium spp.) are toxic plants that contain numerous diterpenoid alkaloids which occur as one of two structural types: (1) lycotonine, and (2) 7,8-methylenedioxylycoctonine (MDL-type). Among the lycoctonine type alkaloids are three N-(methylsuccinimido) anthranoyllycoctonine (MSAL-type) alkaloids which appear to be most toxic: methyllycaconitine (MLA), 14-deacetylnudicauline (DAN), and nudicauline. An ester function at C-18 is an important structural requirement for toxicity. Intoxication results from neuromuscular paralysis, as nicotinic acetylcholine receptors in the muscle and brain are blocked by toxic alkaloids. Clinical signs include labored breathing, rapid and irregular heartbeat, muscular weakness, and collapse. Toxic alkaloid concentration generally declines in tall larkspurs with maturation, but alkaloid concentration varies over years and from plant to plant, and is of little use for predicting consumption by cattle. Knowledge of toxic alkaloid concentration is valuable for management purposes when cattle begin to eat larkspur. Cattle generally begin consuming tall larkspur after flowering racemes are elongated, and consumption increases as larkspur matures. Weather is also a major factor in cattle consumption, as cattle tend to eat more larkspur during or just after summer storms. Management options that may be useful for livestock producers include conditioning cattle to avoid larkspur (food aversion learning), grazing tall larkspur ranges before flowering (early grazing) and after seed shatter (late grazing), grazing sheep before cattle, herbicidal control of larkspur plants, and drug therapy for intoxicated animals. Some potentially fruitful research avenues include examining alkaloid chemistry in low and plains larkspurs, developing immunologic methods for analyzing larkspur alkaloids, developing drug therapy, and devising grazing regimes specifically for low and plains larkspur.

Alkaloids↗

PubMed1999

Pyrrolizidine alkaloid plants, metabolism and toxicity.

More than 350 PAs have been identified in over 6,000 plants in the Boraginaceae, Compositae, and Leguminosae families (Table 1). About half of the identified PAs are toxic and several have been shown to be carcinogenic in rodents. PA-containing plants have worldwide distribution, and they probably are the most common poisonous plants affecting livestock, wildlife, and humans. In many locations, PA-containing plants are introduced species that are considered invasive, noxious weeds. Both native and introduced PA-containing plants often infest open ranges and fields, replacing nutritious plants. Many are not palatable and livestock avoid eating them if other forages are available. However, as they invade fields or crops, plant parts or seeds can contaminate prepared feeds and grains which are then readily eaten by many animals. Human poisonings most often are a result of food contamination or when PA-containing plants areused for medicinal purposes. This is a review of current information on the diagnosis, pathogenesis, and molecular mechanisms of PA toxicity. Additional discussion includes current and future research objectives with an emphasis on the development of better diagnostics, pyrrole kinetics, and the effects of low dose PA exposure.

Animals↗

PubMed1999

Lupines, poison-hemlock and Nicotiana spp: toxicity and teratogenicity in livestock.

Many species of lupines contain quinolizidine or piperidine alkaloids known to be toxic or teratogenic to livestock. Poison-hemlock (Conium maculatum) and Nicotiana spp. including N. tabacum and N. glauca contain toxic and teratogenic piperidine alkaloids. The toxic and teratogenic effects from these plant species have distinct similarities including maternal muscular weakness and ataxia and fetal contracture-type skeletal defects and cleft palate. It is believed that the mechanism of action of the piperidine and quinolizidine alkaloid-induced teratogenesis is the same; however, there are some differences in incidence, susceptible gestational periods, and severity between livestock species. Wildlife species have also been poisoned after eating poison-hemlock but no terata have been reported. The most widespread problem for livestock producers in recent times has been lupine-induced "crooked calf disease." Crooked calf disease is characterized as skeletal contracture-type malformations and occasional cleft palate in calves after maternal ingestion of lupines containing the quinolizidine alkaloid anagyrine during gestation days 40-100. Similar malformations have been induced in cattle and goats with lupines containing the piperidine alkaloids ammodendrine, N-methyl ammodendrine, and N-acetyl hystrine and in cattle, sheep, goats, and pigs with poison-hemlock containing predominantly coniine or gamma-coniceine and N. glauca containing anabasine. Toxic and teratogenic effects have been linked to structural aspects of these alkaloids, and the mechanism of action is believed to be associated with an alkaloid-induced inhibition of fetal movement during specific gestational periods. This review presents a historical perspective, description and distribution of lupines, poison-hemlock and Nicotiana spp., toxic and teratogenic effects and management information to reduce losses.

Alkaloids↗

PubMed1998

Oxidized resin acids in aerosol derived from rosin core solder.

Exposure to rosin during a variety of uses has been associated with dermal and pulmonary sensitization. Oxidized resin acids are present in many rosin products, and have been regarded as the main sensitizing rosin compounds in cases of dermal sensitization. This research describes oxidized resin acids identified in aerosol produced during soldering with rosin core solder. Oxidized resin acids found were 7-oxodehydroabietic acid, 15-hydroxydehydroabietic acid, and 7-hydroxydehydroabietic acid. The presence of oxidized compounds known to be dermal sensitizers in aerosol from rosin flux soldering supports the hypothesis that resin acid compounds are pulmonary sensitizers as previously proposed. Changes in the composition of resin acid aerosol derived from heated rosin core solder (compared with the parent material) are described.

Abietanes↗

PubMed1998

Tissue swainsonine clearance in sheep chronically poisoned with locoweed (Oxytropis sericea).

Locoweed poisoning is seen throughout the world and annually costs the livestock industry millions of dollars. Swainsonine inhibits lysosomal alpha-mannosidase and Golgi mannosidase II. Poisoned animals are lethargic, anorexic, emaciated, and have neurologic signs that range from subtle apprehension to seizures. Swainsonine is water-soluble, rapidly absorbed, and likely to be widely distributed in the tissues of poisoned animals. The purpose of this study was to quantify swainsonine in tissues of locoweed-poisoned sheep and determine the rate of swainsonine clearance from animal tissues. Twenty-four crossbred wethers were gavaged with ground Oxytropis sericea to obtain swainsonine doses of 1 mg swainsonine x kg(-1) BW x d(-1) for 30 d. After dosing, the sheep were killed on d 0, 1, 2, 3, 4, 6, 14, 30, 60, and 160. Animal weights and feed consumption were monitored. Serum was collected during dosing and withdrawal periods, and tissues were collected at necropsy. Serum swainsonine concentrations were determined using an alpha-mannosidase inhibition assay. Swainsonine concentrations in skeletal muscle, heart, brain, and serum were similar at approximately 250 ng/g. Clearance from these tissues was also similar, with half-lives (T(1/2)) of less than 20 h. Swainsonine at more than 2,000 ng/g, was detected in the liver, spleen, kidney, and pancreas. Clearance from liver, kidney, and pancreas was about T(1/2) 60 h. These findings imply that poisoned sheep have significant tissue swainsonine concentrations and animals exposed to locoweed should be withheld from slaughter for at least 25 d (10 T(1/2)) to ensure that the locoweed toxin has cleared from animal tissues and products.

Animals↗

PubMed1998

Teratogenic and fetotoxic effects of two piperidine alkaloid-containing lupines (L. formosus and L. arbustus) in cows.

Cleft palate and minor front limb contractures were induced in calves by maternal ingestion of the piperidine alkaloid-containing lupines, Lupinus formosus and L. arbustus. Crooked calf disease, which includes an occasional cleft palate, is a congenital condition of widespread occurrence in cattle in the western U.S. and Canada. It is known to occur after maternal ingestion of certain species of Lupinus during specific gestational periods. Although many lupine species contain quinolizidine alkaloids including the teratogenic alkaloid anagyrine, L. formosus and L. arbustus produce piperidine alkaloids including the reported teratogen ammodendrine. In addition to ammodendrine, L. formosus contains both N-acetyl hystrine and N-methyl ammodendrine, whereas L. arbustus contains ammodendrine, trace amounts of N-methyl ammodendrine, and no N-acetyl hystrine. L. formosus and L. arbustus were fed to pregnant cows at equivalent ammodendrine doses during a 10-day period from days 40-50 of gestation. One calf from a cow fed L. formosus had a full cleft palate. Embryonic death and resorption of one fetus and minor front limb contractures (arthrogryposis) in another calf occurred with two cows fed L. arbustus. Alkaloid analysis of blood samples taken during the feeding period, and up to and including 48 hours after the last dose, demonstrated comparative plasma elimination times with N-methyl ammodendrine > ammodendrine > N-acetyl hystrine. The objectives of this experiment were to: 1) determine if N-acetyl hystrine is a potential teratogen; and 2) define the narrow cleft palate induction period in cows.

Alkaloids↗

PubMed1998

Abortifacient effects of lodgepole pine (Pinus contorta) and common juniper (Juniperus communis) on cattle.

Lodgepole pine (Pinus contorta) and common juniper (Juniperus communis) contain high levels of isocupressic acid that has been identified as the abortifacient component of ponderosa pine needles in cattle. Therefore, the abortifacient potential of P contorta and J communis needles was tested in feeding trials with pregnant cattle. Cows (2 groups of 2 each) were fed by gavage 4.5-5.5 kg/d ground dry needles from either P contorta or J communis starting on gestation day 250. Isocupressic acid (ICA) levels in P contorta needles and J communis plant material were 0.8 and 2.0% (dry weight) respectively. Cows fed P contorta received a daily dose of 62-78 mg ICA/kg body weight and aborted after 8 and 10 d. The 2 cows fed J communis received a daily dose of 190 and 245 mg ICA/kg body weight and aborted after 3 and 4 days respectively. All cows retained fetal membranes and had classical clinical signs of pine needle-induced abortion. Pinus ponderosa, P contorta, J communis, and Cupressus macrocarpa samples were also analyzed for the presence of myristate and laurate esters of 1,14-tetradecanediol and 1,12-dodecanediol. These lipid like compounds of P ponderosa have potent vasoconstrictive activity in a placentome perfusion assay and are proposed as possible abortifacients in cattle. Concentration of the vasoactive lipids were 0.028% (P ponderosa), 0.023% (P contorta), 0.001% (J communis), and none detected (C macrocarpa). It was concluded that these compounds are not required for the plant material to be abortifacient in cattle.

Abortifacient Agents↗

PubMed1997

Detection of resin acid compounds in airborne particulate generated from rosin used as a soldering flux.

Various uses of rosin and exposure to its resin acid constituents have been associated with dermal and pulmonary sensitization. Methodology is presented to detect resin acids common to rosin (such as abietic and dehydroabietic acid) found in aerosol from heated rosin flux. Air filtration, solvent filter extraction, and gas chromatography/mass spectrometry were used to provide qualitative and quantitative information on the resin acid content of aerosol produced during soldering with rosin flux. Abietic acid and dehydroabietic acid were identified and quantified in aerosol derived from heated rosin flux, in samples collected in the field and in laboratory generated samples. Other resin acids (including several apparently oxidized resin acids) were detected, but not quantified. Laboratory mass balance experiments using soldering temperatures and liquid rosin flux showed that much of the nonvolatile material originally present in unheated flux may be captured on a sampling filter following heating and aerosolization. The data presented suggest that resin acids are a major component (with regard to mass) of the airborne contaminants produced during soldering with rosin flux. Abietic acid was shown to be unstable on sampling filters held for a period of weeks, while dehydroabietic acid and total solvent-soluble material were not found to degrade under the same conditions. Rosin aerosol produced in the laboratory using a soldering iron and liquid rosin flux produced particles shown to be of respirable size using scanning electron microscopy.

Abietanes↗

PubMed1996

The toxic and abortifacient effects of ponderosa pine.

Ponderosa pine needles cause abortion and a poorly described toxicosis when eaten by cattle. In previous trials, the abortifacient compound of pine needles was identified as isocupressic acid. At abortifacient doses, isocupressic acid caused no other toxicosis. However, other pine needle fractions, similar in composition to several commercially available rosin products, caused no abortion but were very toxic. The purpose of this study was to describe the toxicoses of ponderosa pine, compare its toxicity with other rosin and related pine products, and identify the toxin. Four groups of three pregnant beef cows each were treated with either ponderosa pine tips, rosin gum, dehydroabietic acid, or ground alfalfa. The cows treated with pine tips aborted, had retained placentas with endometritis, and developed both renal and neurologic lesions. The cattle treated with rosin gum or dehydroabietic acid did not abort but developed similar signs and lesions of intoxication. Clinical signs of intoxication included anorexia, mild rumen acidosis, dyspnea, paresis progressing to paralysis, and death. Clinical biochemical results, suggestive of renal, hepatic, and muscular disease, included azotemia, hypercreatinemia, hyperphosphatemia, proteinuria, and marked elevations of various serum enzymes. Histologically, all poisoned animals had nephrosis, vacuolation of basal ganglia neuropil with patchy perivascular and myelinic edema, and skeletal myonecrosis. The alfalfa-treated controls were normal. These findings suggest that ponderosa pine needles and tips are both abortifacient and toxic. Because the lesions caused by pine tips, rosin gum, and dehydroabietic acid are similar, toxicosis is most likely due to the diterpene abietane acids, common in all three.

Abietanes↗