Induction and transfer of resistance to poisoning by Amorimia (Mascagnia) septentrionalis in goats.

Amorimia septentrionalis contains sodium monofluoroactetate (MFA) and can cause acute heart failure in ruminants when ingested in toxic doses. In this study, we demonstrate that resistance to poisoning by A. septentrionalis can be improved in goats by the repeated administration of non-toxic doses of A. septentrionalis. We also show that increased resistance to poisoning by A. septentrionalis can also be achieved by the transfaunation of ruminal content from goats previously conditioned to be resistant to naïve goats. These methods of improving resistance require further study, but appear to provide potential management solutions to mitigate toxicity problems from A. septentrionalis, and perhaps other plant species containing MFA.

Poisonous plants: effects on embryo and fetal development.

Poisonous plant research in the United States began over 100 years ago as a result of livestock losses from toxic plants as settlers migrated westward with their flocks, herds, and families. Major losses were soon associated with poisonous plants, such as locoweeds, selenium accumulating plants, poison-hemlock, larkspurs, Veratrum, lupines, death camas, water hemlock, and others. Identification of plants associated with poisoning, chemistry of the plants, physiological effects, pathology, diagnosis, and prognosis, why animals eat the plants, and grazing management to mitigate losses became the overarching mission of the current Poisonous Plant Research Laboratory. Additionally, spin-off benefits resulting from the animal research have provided novel compounds, new techniques, and animal models to study human health conditions (biomedical research). The Poisonous Plant Research Laboratory has become an international leader of poisonous plant research as evidenced by the recent completion of the ninth International Symposium on Poisonous Plant Research held July 2013 in Hohhot, Inner Mongolia, China. In this article, we review plants that negatively impact embryo/fetal and neonatal growth and development, with emphasis on those plants that cause birth defects. Although this article focuses on the general aspects of selected groups of plants and their effects on the developing offspring, a companion paper in this volume reviews current understanding of the physiological, biochemical, and molecular mechanisms of toxicoses and teratogenesis.

Influences of plant toxins and their spatial distribution on foraging by the common brushtail possum, a generalist mammalian herbivore.

Generalist herbivores forage on a variety of plant species, allowing them to gain nutrients while limiting ingestion of harmful toxins. As the capacity to mix diets appears important for maximizing intake, the spatial scale in heterogeneity of food resources should influence the foraging behavior of herbivores. Our aim was to identify how the feeding strategy of a generalist mammalian herbivore, the common brushtail possum, responds to foods within a spatially defined environment. We evaluated foraging responses against increasing spatial separation between pairs of artificial diets that differed in flavor and toxin profile, to determine how distance and diet affect intake and behavior. Foraging responses were influenced by the type of diet or the degree of spatial separation between foods but not by their interaction. Diet influenced intake, time spent feeding, and feeding rate, but had no effect on nightly foraging interval, number of feeding bouts, or bout length. The number of switches between paired food resources and foraging efficiency (intake per unit distance, which accounts for the energetic costs of travelling), were influenced only by distance. Titrating foraging against a range of distances demonstrated how quickly foraging efficiency can decline in response to the spatial separation of food resources, highlighting the importance of spatial heterogeneity of plants within the home range of an herbivore.

Drying and processing protocols affect the quantification of cyanogenic glucosides in forage sorghum.

BACKGROUND: Cyanogenic glucosides are common bioactive products that break down to release toxic hydrogen cyanide (HCN) when combined with specific ß-glucosidases. In forage sorghum, high concentrations of the cyanogenic glucoside dhurrin lead to reduced productivity and sometimes death of grazing animals, especially in times of drought, when the dhurrin content of stunted crops is often higher. The aim of this study was to develop harvesting protocols suitable for sampling in remote areas. RESULTS: Dhurrin concentration in air- and oven-dried leaves was the same as in fresh leaves, with no subsequent losses during storage. Dhurrin concentration was halved when leaves were freeze-dried, although activity of the endogenous dhurrinase was preserved. Direct measurement of dhurrin concentration in methanolic extracts using liquid chromatography/mass spectrometry (LC/MS) gave similar results to methods that captured evolved cyanide. A single freezing event was as effective as fine grinding in facilitating complete conversion of dhurrin to cyanide. CONCLUSION: Direct measurement of dhurrin using LC/MS is accurate but expensive and not appropriate for fieldwork. Air drying provides an accurate, low-cost method for preparing tissue for dhurrin analysis, so long as the specific ß-glucosidase is added. It is recommended that comparative studies like the one presented here be extended to other cyanogenic species.

Genetic diversity analysis of cyanogenic potential (CNp) of root among improved genotypes of cassava using simple sequence repeat markers.

Cyanogenic potential (CNp) of cassava constitutes a serious problem for over 500 million people who rely on the crop as their main source of calories. Genetic diversity is a key to successful crop improvement for breeding new improved variability for target traits. Forty-three improved genotypes of cassava developed by International Institute of Tropical Agriculture (ITA), Ibadan, were characterized for CNp trait using 35 Simple Sequence.Repeat (SSR) markers. Essential colorimetry picric test was used for evaluation of CNp on a color scale of 1 to 14. The CNp scores obtained ranged from 3 to 9, with a mean score of 5.48 (+/- 0.09) based on Statistical Analysis System (SAS) package. TMS M98/ 0068 (4.0 +/- 0.25) was identified as the best genotype with low CNp while TMS M98/0028 (7.75 +/- 0.25) was the worst. The 43 genotypes were assigned into 7 phenotypic groups based on rank-sum analysis in SAS. Dissimilarity analysis representatives for windows generated a phylogenetic tree with 5 clusters which represented hybridizing groups. Each of the clusters (except 4) contained low CNp genotypes that could be used for improving the high CNp genotypes in the same or near cluster. The scatter plot of the genotypes showed that there was little or no demarcation for phenotypic CNp groupings in the molecular groupings. The result of this study demonstrated that SSR markers are powerful tools for the assessment of genetic variability, and proper identification and selection of parents for genetic improvement of low CNp trait among the IITA cassava collection.

The syndromic classification, differential diagnosis, management, and prevention of potentially fatal plant poisonings in Louisiana and the Gulf South.

The American Association of Poison Control Centers has reported more than 50,000 calls annually relating to plant exposures, usually non-lethal ingestions in young adults, adolescents, and children. In addition, there has been more than a 100% increase in the mortality rate for unintentional poisonings in the United States (US) between 1999 and 2006, especially in males and in individuals aged 15-29 years. For children, the frequency of plant exposures is directly related to their presence and abundance in households. In contrast, adolescents and young adults may experiment with naturally hallucinogenic plants, often obtained over the Internet, or attempt suicide by ingesting poisonous plants. In light of these recent trends in plant poisonings, the objectives of this investigation will be to propose a rapid syndromic classification scheme of only four types of highly toxic plants (cardiotoxic, neurotoxic, cytotoxic, and gastrointestinal/hepatotoxic) for the initial evaluation of patients poisoned by indigenous and often unidentified toxic plants in Louisiana and the Gulf South. It will also discuss current strategies for early diagnosis, management, and prevention of potentially lethal plant poisonings. Although many plants contain toxins, plants provide more than 70% of new drugs today and continue to provide new therapies for infectious diseases and cancer. More leisure time spent outdoors seeking natural foods and surfing the Internet for natural substances to abuse will create more opportunities for plant poisonings among high-risk groups, such as immigrants foraging for greens and adolescents experimenting with natural hallucinogens.

Variability of yellow tulp (Moraea pallida Bak.) toxicity.

Yellow tulp (Moraea pallida Bak.), collected predominantly during the flowering stage from a number of sites in South Africa, showed large variation in digoxin equivalent values, indicating variability in yellow tulp toxicity. Very low values were recorded for tulp collected from certain sites in the Northern Cape.

[Pyrrolizidine alkaloids and seneciosis in farm animals. Part 2: clinical signs, species-specific sensitivity, food residues, feed contamination, limit values]. / Pyrrolizidinalkaloide und die Seneciose bei Tieren. Teil 2: Klinik, Speziesunterschiede, Rückstandsverhalten, Futtermittelkontamination und Grenzwerte.

At the forefront of pyrrolizidine alkaloid (PA) poisoning is the chronic ingestion of contaminated hay, which causes liver damage resulting in an ongoing fatal liver cirrhosis or in the veno-occlusive disease in liver or lung, respectively. The symptomatology of PA-poisoning is not identical for all animal species, and also includes central nervous symptoms. In affected horses significantly elevated levels of hepatogenic serum enzymes and an increase of the retention time for bromosulfophthalein indicates the fatal outcome of the intoxication. Chronic seneciosis of horses is incurable. Rabbits, Japanese quails, and guinea pigs are regarded as poison-resistant species. Sheep and in particular goats are insensitive unless extremely high amounts of plants which exceed the animal's body weight by several-fold are ingested. In contrast, pigs, cattle, and horses as well as chicken and likewise man are very sensitive to poisonings by PA-containing plants. In sensitive animal species a very small amount of contaminated dry hay is needed to exceed the daily dose of 1µg/kg body weight PA which is taken as harmless for man by health authorities. Therefore, all feed with visible pieces of Senecio jacobaea plants are not acceptable as animal fodder and should be destroyed.

Ricin poisoning: A review on contamination source, diagnosis, treatment, prevention and reporting of ricin poisoning.

INTRODUCTION: Ricin, a toxic glycoprotein derived from the castor bean plant, is one of the most potent poisons known in the world. Ricin intoxication is a fatal and uncommon medical condition and recently its use as a potential bioterrorism agent has also been reported. This study aims to identify the main characteristics of diagnosed ricin poisoning cases worldwide in order to raise awareness of this toxin among the population and clinicians. METHODS: A collection of human case studies of ricin intoxication in the world was produced. The databases Pubmed, Sciencedirect and Google Scholar were used to extract articles from January 1980 to June 2020. RESULTS: Fifty ricin-intoxicated patients worldwide described in the literature have been identified. Most cases were found in Asia (19 cases), Europe (12 cases) and America (15 cases). Intoxication was mostly accidental (37 cases). Intoxication by castor bean is characterized by acute gastroenteritis-like disease as primary manifestations leading to severe fluid and electrolyte imbalance. The mechanism of death was peripheral vascular collapse and progressing multiple organ failure occurring 10h-72h after intoxication. The questioning of patients and family made it possible to retrieve an history of castor seeds or castor oil ingestion Patients received symptomatic treatment consisting mostly to rehydration with intravenous fluids and digestive decontamination performed with activated charcoal and/or gastric lavage within one day after the ingestion, to reduce gastrointestinal absorption of ricin. This decontamination treatment administered early has been very effective. Only six deaths were observed. DISCUSSION: Currently, no antidote, vaccine, or other specific effective treatment is available for ricin poisoning or prevention. Prompt treatment with supportive care was necessary to limit morbidity and mortality. To date, patient education is essential to prevent this accidental poisoning. CONCLUSION: Clinicians and health care professionals should have a high level of suspicion when faced with an outbreak of serious respiratory or gastrointestinal illness.

Toxin Degradation by Rumen Microorganisms: A Review.

Animal feeds may contain exogenous compounds that can induce toxicity when ruminants ingest them. These toxins are secondary metabolites originating from various sources including plants, bacteria, algae and fungi. Animal feed toxins are responsible for various animal poisonings which negatively impact the livestock industry. Poisoning is more frequently reported in newly exposed, naïve ruminants while 'experienced' ruminants are observed to better tolerate toxin-contaminated feed. Ruminants can possess detoxification ability through rumen microorganisms with the rumen microbiome able to adapt to utilise toxic secondary metabolites. The ability of rumen microorganisms to metabolise these toxins has been used as a basis for the development of preventative probiotics to confer resistance against the poisoning to naïve ruminants. In this review, detoxification of various toxins, which include plant toxins, cyanobacteria toxins and plant-associated fungal mycotoxins, by rumen microorganisms is discussed. The review will include clinical studies of the animal poisoning caused by these toxins, the toxin mechanism of action, toxin degradation by rumen microorganisms, reported and hypothesised detoxification mechanisms and identified toxin metabolites with their toxicity compared to their parent toxin. This review highlights the commercial potential of rumen inoculum derived probiotics as viable means of improving ruminant health and production.

Poisonous plants.

South Africa is blessed with one of the richest floras in the world, which--not surprisingly--includes many poisonous plants. Theiler in the founding years believed that plants could be involved in the aetiologies of many of the then unexplained conditions of stock, such as gousiekte and geeldikkop. His subsequent investigations of plant poisonings largely laid the foundation for the future Sections of Toxicology at the Institute and the Faculty of Veterinary Science (UP). The history of research into plant poisonings over the last 100 years is briefly outlined. Some examples of sustained research on important plant poisonings, such as cardiac glycoside poisoning and gousiekte, are given to illustrate our approach to the subject and the progress that has been made. The collation and transfer of information and the impact of plant poisonings on the livestock industry is discussed and possible avenues of future research are investigated.

Poison Ivy, Oak, and Sumac Dermatitis: What Is Known and What Is New?

Poison ivy, poison oak, and poison sumac are the most common causes of clinically diagnosed allergic contact dermatitis in North America. Approximately 50% to 75% of the US adult population is clinically sensitive to poison ivy, oak, and sumac. We reviewed the botany and history of these plants; urushiol chemistry and pathophysiology, clinical features, and the prevalence of allergic contact dermatitis caused by these plants; and current postexposure treatment and preventive methods, including ongoing investigations in the development of a vaccine (immunotherapy). Although extensive efforts have been made to develop therapies that prevent and treat contact dermatitis to these plants, there lacks an entirely effective method, besides complete avoidance. There is a need for a better therapy to definitively prevent allergic contact dermatitis to these plants.

Sequential administrations of trifluoroacetate induce tolerance to Palicourea maccgravii, a monofluoroacetate-containing plant, in calves.

Monofluoroacetate (MFA) is considered one of the most toxic substances known. It is found naturally in plants, and causes sudden death syndrome in ruminants. Due to hyperacute evolution of poisoning and the absence of effective treatment, induction of resistance in animals might be the best tool to control MFA poisoning in ruminants. The objective of this study was to promote resistance in cattle against the toxic effects of MFA through its degradation by the ruminal microbiota after the administration of sodium trifluoroacetate (TFA). Ten calves were distributed into two groups: control group (n = 3) and treated group (n = 7). The calves in the treated group received 0.1 mg/kg live weight of TFA, whereas, those in the control group received water; both for 28 consecutive days. The calves were subjected to daily clinical evaluation and weekly blood biochemical determination to identify any signs of poisoning. After 28 d of administration of TFA or water, 2.0 g/kg body weight of Palicourea marcgravii leaves (containing 0.15% MFA) were administered using a stomach tube to determine the occurrence of resistance. The administration of TFA did not induce any clinical or biochemical changes in blood. The administration of P. marcgravii induced clinical changes in the calves of control group, but there was no change in the calves of the treated group. In conclusion, the administration of TFA to cattle can induce effective resistance against MFA poisoning.

Effects of endophyte-infected tall fescue seed and protein supplementation on stocker steers: I. Growth performance and hemodynamic responses.

Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue and is detrimental to growth and performance. Recent research has shown that supplementing protein has the potential to enhance growth performance in weaned steers. Therefore, the objective of this study was to evaluate the effect of supplemental CP on physiological parameters in stocker steers experiencing fescue toxicosis. Thirty-six weaned Angus steers (6 mo of age) stratified by weight (196.1 ± 3.6 kg) were assigned to a 2 × 2 factorial arrangement for 56 d: endophyte-free (EF) seed and 14% CP (EF-14; n = 9), EF seed and 18% CP (EF-18; n = 9), endophyte-infected (EI) seed and 14% CP (EI-14; n = 9), and EI seed and 18% CP (EI-18; n = 9). Steer growth and hemodynamic responses were collected weekly during ergot alkaloid exposure. On day 14 of the trial, iButton temperature data loggers were subcutaneously inserted in the lateral neck region to record hourly body temperature for 42 d. Data were analyzed using PROC MIXED of SAS with repeated measures. No differences were observed in DMI, BW, ADG, F:G, or BCS during the treatment period (P > 0.05). Hair shedding scores, rectal temperatures, surface temperatures, and respiration rates were greater in EI steers compared to EF steers regardless of supplemental CP (P < 0.05). However, subcutaneous body temperature was greater in EI-14 steers (37.94 °C) compared to other steer groups (37.60, 37.68, 37.72 ± 0.04 °C for EF-14, EF-18, and EI-18, respectively; P < 0.05). Prolactin concentrations tended to be greater in EF steers when compared to EI steers (P = 0.07). Heart rate and hematocrit were reduced for EI-18 steers compared to other steer groups (P < 0.05). Caudal artery diameter was reduced in EI-18 steers compared to EI-14 steers (2.60 vs. 2.75 ± 0.05 mm, respectively; P < 0.05) and caudal vein diameter was reduced in EI-18 steers (3.20 mm) compared to all other steer groups (3.36, 3.39, 3.50 mm for EF-14, EF-18, and EI-14, respectively; P < 0.05). However, there was no difference observed in systolic or diastolic blood pressure during the treatment period (P > 0.05). Based on the data, exposure to low to moderate levels of ergot alkaloids during the stocker phase had a negative impact on hemodynamic responses and supplemental CP had minimal impact to alleviate symptoms. Therefore, feeding additional protein above established requirements is not expected to help alleviate fescue toxicosis.

Effect of grinding and long-term storage on the toxicity of white snakeroot (Ageratina altissima) in goats.

White snakeroot (Ageratina altissima) contains the putative toxin tremetone and can produce a disease called "trembles" or "milk sickness". However the toxicity of tremetone has not been demonstrated in vivo. It has been reported that the plant is less toxic after drying and grinding. The objectives of these studies were to determine: 1) the toxic effect of grinding white snakeroot 4 months prior to dosing and, 2) the toxic effect of storing white snakeroot at ambient temperature for 5 years. Dried white snakeroot, ground 1 day, 1 month, and 4 months prior to dosing, was orally gavaged to goats at 2% of their body weight for up to 28 days or until they were minimally poisoned (minimal muscular weakness and increased serum creatine kinase (CK) activities). All four goats dosed with white snakeroot that had been ground 4 months previously and stored at room temperature were poisoned, became exercise intolerant, and had increased serum CK activities (>5600 U/ L). White snakeroot stored for 5 years was toxic as 3 of 5 dosed goats developed clinical disease within only 6 days of dosing even though approximately 80% of the tremetone in the plant had disappeared during the 5-year storage period. The results from this study demonstrate that previous grinding and extended storage did not significantly alter white snakeroot toxicity. The results also indicate that tremetone concentration is not the singular indicator of toxicity and that other white snakeroot toxins or toxic tremetone degradation products remain in dried, stored white snakeroot.

An agent-based model of cattle grazing toxic Geyer's larkspur.

By killing cattle and otherwise complicating management, the many species of larkspur (Delphinium spp.) present a serious, intractable, and complex challenge to livestock grazing management in the western United States. Among the many obstacles to improving our understanding of cattle-larkspur dynamics has been the difficulty of testing different grazing management strategies in the field, as the risk of dead animals is too great. Agent-based models (ABMs) provide an effective method of testing alternate management strategies without risk to livestock. ABMs are especially useful for modeling complex systems such as livestock grazing management, and allow for realistic bottom-up encoding of cattle behavior. Here, we introduce a spatially-explicit, behavior-based ABM of cattle grazing in a pasture with a dangerous amount of Geyer's larkspur (D. geyeri). This model tests the role of herd cohesion and stocking density in larkspur intake, finds that both are key drivers of larkspur-induced toxicosis, and indicates that alteration of these factors within realistic bounds can mitigate risk. Crucially, the model points to herd cohesion, which has received little attention in the discipline, as playing an important role in lethal acute toxicosis. As the first ABM to model grazing behavior at realistic scales, this study also demonstrates the tremendous potential of ABMs to illuminate grazing management dynamics, including fundamental aspects of livestock behavior amidst ecological heterogeneity.

Yellow Oleander Seed, or "Codo de Fraile" (Thevetia spp.): A Review of Its Potential Toxicity as a Purported Weight-Loss Supplement.

The Dietary Supplements and Health Education Act (DSHEA), passed by the United States Congress in October of 1994, defines herbal products as nutritional supplements, not medications. This opened the market for diverse products made from plants, including teas, extracts, essential oils, and syrups. Mexico and the United States share an extensive border, where diverse herbal products are available to the public without a medical prescription. Research undertaken in the neighboring cities of Ciudad Juarez, Mexico, and El Paso, Texas, USA, shows the use of herbs is higher in this border area compared to the rest of the United States. A portion of the population is still under the erroneous impression that "natural" products are completely safe to use and therefore lack side effects. We review the dangers of ingesting the toxic seed of Thevetia spp. (family Apocynaceae), commonly known as "yellow oleander" or "codo de fraile," misleadingly advertised on the Internet as an effective and safe dietary supplement for weight loss. Lack of proper quality control regarding herbs generates a great variability in the quantity and quality of the products' content. Herb-drug interactions occur between some herbal products and certain prescription pharmaceuticals. Certain herbs recently introduced into the U.S. market may not have been previously tested adequately for purity, safety, and efficacy. Due to the lack of reliable clinical data regarding the safe use of various herbal products currently available, the public should be made aware regarding the possible health hazards of using certain herbs for therapeutic purposes. The potentially fatal toxicity of yellow oleander seed is confirmed by cases reported from various countries, while the purported benefits of using it for weight loss have not been evaluated by any known clinical trials. For this reason, the use of yellow oleander seed as a dietary supplement should be avoided.

A potential krimpsiekte vaccine.

Krimpsiekte, a chronic form of cardiac glycoside poisoning, is an important plant-induced intoxication of small stock in South Africa. It is caused by cumulative, neurotoxic bufadienolides, such as cotyledoside. A cotyledoside-bovine serum albumin conjugate was synthesized to immunize animals. The efficacy of the cotyledoside-conjugate in inducing an immunological response was ascertained in rabbits (n = 4) and sheep (n = 4) by determining cotyledoside antibody titres with an ELISA using cotyledoside-hen ovalbumin as antigen. The formation of anticotyledoside antibodies was induced in both rabbits and sheep following immunization with the cotyledoside-protein conjugate. Protection provided by the vaccine was demonstrated by challenging sheep (n = 4) with repeated, daily doses of cotyledoside (0.015 mg/kg) administered intravenously, commencing 45 days after the initial vaccination. One control animal died on Day 3 of the challenge period and the other was severely affected after administration of the third cotyledoside dose. The immunized ewes (n = 2) remained clinically unaffected and the challenge was suspended following six daily injections. Vaccination as a means of preventing krimpsiekte seems to be quite feasible and deserves further investigation.

A chimeric protein of abrin and Abrus precatorius agglutinin that neutralizes abrin mediated lethality in mice.

Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication. The design was based on the inclusion of the immunogenic region of the full length protein and the minimal essential folding domains required for inducing neutralizing antibody response. The chimera also contains the epitope for the only two neutralizing antibodies; D6F10 and A7C4, reported against abrin till now. Active immunization with the chimera protected all the mice challenged with 45 X LD50 of abrin. Also, passive transfer of antibodies raised against the chimera rescued all mice challenged with 50 X LD50 of toxin. Hence the chimeric protein appears to be a promising vaccine candidate against abrin induced lethality.