Ruminant metabolism of zygacine, the major toxic alkaloid in foothill death camas (Zigadenuspaniculatus).

Death Camas (Zigadenus spp.) are common poisonous plants distributed throughout North America. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. Both cattle and sheep can be poisoned by grazing death camas, however, sheep consume death camas more readily and are most often poisoned. We hypothesized that the presence of enzymes, including esterases present in the rumen, liver, and blood of livestock would metabolize zygacine. The objective of this study was to investigate the metabolism of zygacine in sheep and cattle using in-vitro and in-vivo systems. Results from experiments where zygacine was incubated in rumen culture, plasma, liver S9 fractions, and liver microsomes and from the analysis of rumen and sera from sheep and cattle dosed death camas plant material demonstrated that zygacine is metabolized to zygadenine in the rumen, liver and blood of sheep and cattle. The results from this study indicate that diagnosticians should analyze for zygadenine, and not zygacine, in the rumen and sera for the diagnosis of livestock suspected to have been poisoned by foothill death camas.

Death of Socrates: a likely case of poison hemlock (Conium maculatum) poisoning.

INTRODUCTION: The death of Socrates in 399 BCE is described in Plato's dialogue, the Phaedo, written an unknown time afterwards from accounts by others. THE EVIDENCE: Socrates' death has almost always been attributed to his drinking an extract of poison hemlock, Conium maculatum, despite apparent discrepancies between the clinical features described in classical translations of the Phaedo and general clinical experience of poisoning with the toxic alkaloids it contains. EVALUATION: Recent acute philological analysis of the original Greek text has resolved many of the discrepancies by showing that the terms used in the classical translations were misinterpretations of the clinical signs described. It is also likely that the unpleasant clinical effects, such as vomiting, abdominal pain, diarrhoea and muscle fasciculation commonly described in modern reports of poison hemlock poisoning, were not mentioned to present the death of Socrates in a way consistent with his philosophical ideals and those of his pupil Plato. CONCLUSIONS: Seen in this way, the death of Socrates can be accepted as a limited case report of Conium maculatum poisoning. Even after reaching that conclusion, intriguing scientific questions remain about the toxicity of the coniine alkaloids and the mechanisms of their effects.

DNA barcoding as new diagnostic tool to lethal plant poisoning in herbivorous mammals.

Reliable identification of plant species in the digestive tract of a deceased animal often represents the major key to diagnose a lethal intoxication with poisonous plants in veterinary pathology. In many cases, identification of the species is challenging or even impossible because the diagnostic morphological features have been degraded, and because the interpretation of such features requires a considerable expertise in plant anatomy and biodiversity. The use of DNA barcoding markers can support or even replace classical morphological assessment. While these markers have been widely used for plant taxonomy, their forensic application to clarify causes of animal poisoning is novel. In addition, we use specific single-nucleotide polymorphisms as fingerprints. This allows for a clear decision even in cases, where the conventionally used statistical e-values remain ambiguous. In the current work, we explore the feasibility of this strategy in a couple of exemplary cases, either in concert with anatomical diagnostics, or in cases where visual species identification is not possible, or where chemical toxin detection methods are not well established, complex, time consuming and expensive.

[One case of acute poisoning with stramonium].

This paper reported 1 case of poisoning caused by stramonium. Cases of Datura poisoning have been reported nationwide, Its effect on the central nervous system of patients is characterized by first excitation and then inhibition, clinical manifestations include decreased gland secretion, dilated pupils, and tachycardia, etc. Its poisoning mechanism is anticholinergic effect, the effect on Peripheral nervous system is to inhibit Parasympathetic nervous system. Hemoperfusion combined with neostigmine anticholinergic therapy at the early stage of poisoning can effectively improve the clinical symptoms of patients in a short time.

Two Cases of Suspected Poisoning With Goat's Rue (Galega officinalis L.) in Horses.

The present report describes two novel cases of suspected intoxication with Galega officinalis in 6- and 21-year-old Arabian mares displaying acute respiratory signs. Both animals showed signs of pulmonary edema at physical examination, with the oldest of the two also manifesting severe dyspnea and foamy nasal discharge. The mares were grazing on the same meadow with hay available ad libitum. Botanical analysis of the latter showed traces of the toxic plant Galega officinalis (L.), which has been daily ingested at a dose of around 14 g of dry matter for three days. Based on the respiratory signs and the presence of goat's rue in the mares' feed, a presumptive diagnosis of plant poisoning was assumed. Dietary change and treatment allowed the 6-year-old mare to fully recover in 3 days while a longer period of about 2 weeks was necessary for the older horse. Horses avoid eating fresh goat's rue as its palatability is low, yet poisoning may still happen in these species when the plant is found in dried and processed feed material.

[Colchicum poisoning by confusion with wild garlic (Allium ursinum)]. / Intoxication au colchique par confusion avec l'ail des ours.

INTRODUCTION: Colchicine poisoning is a life-threatening intoxication. CASE REPORT: We report a case of food poisosing with Colchicum autumnale by confusion with wild garlic. The clinical presentation is the same as that of colchicine drug intoxication. The evolution can be fatal in case of massive ingestion. The proximity of the place of growth and their similar appearance in spring make Colchicum and wild garlic plants that can easily be confused. CONCLUSION: Physicians have to be vigilant in case of dysenteric syndrome and biological disturbances in spring and look for the consumption of perennial plant preceding symptoms.

Analytical documentation of an Arabian horse fatality related to Oenanthe crocata poisoning.

Analytical detection of Oenanthe crocata toxins in biological samples is challenging because of their instability, the lack of commercially available standards and the exceptionally low detection of these molecules using mass spectrometry. This work aims to report the used analytical methods that allowed identification of the main plant toxins in biological samples from an equid (an Arabian horse) fatality related to hemlock water dropwort (Oenanthe crocata Linnaeus) intake. Using both LC-DAD and LC-HRMS methods allowed identification (i) of oenanthotoxin in roots found on the site, root fragments found in the stomach, stomach content, kidney, and liver, and (ii) of the hydrogenated metabolite of oenanthotoxin (2,3-dihydro-oenanthotoxin) in roots found on the site, root fragments found in the stomach, stomach content, kidney, liver and spleen. Reported analytical data about Oenanthe crocata toxins can be useful for identification of the ingested plant and for supporting a poisoning diagnosis in such cases.

Multiple organ failure leading to death after ingestion of Caltha palustris: A case report.

RATIONALE: Studies have previously reported misidentifying Caltha palustris (C. palustris) as Ligularia fischeri and its subsequent ingestion leading to abdominal pain and gastrointestinal symptoms, which are alleviated immediately. Bradycardia and hypotension may persist for several days, and an infusion of dopamine can restore a healthy state without complications. We report a case of C. palustris poisoning with protein-losing enteropathy that has not been reported previously. The patient died of multiple organ failure, and exhibited more severe clinical deterioration than previous cases due to prolonged shock. PATIENT CONCERNS: A 70-year-old woman was admitted to the emergency department (ED) with complaints of epigastric pain, vomiting, and diarrhea after ingestion of a poisonous plant presumed to be C. palustris. The patient presented with bradycardia and hypotension after ED admission, and vasopressor infusion improved bradycardia but not hypotension, while the patient complained of severe epigastric pain. DIAGNOSES: Abdominal computed tomography showed luminal distention and edematous thickening of the entire stomach lining, as well as small and large intestinal wall edema, indicating severe gastritis and enterocolitis. The laboratory test results suggested severe hypoalbuminemia, while the arterial blood gas analyses showed a continuous increase in metabolic acidosis. INTERVENTIONS: As plant poisoning was suspected, activated charcoal was administered to the patient, followed by administration of vasopressors and other conservative therapies. Continuous renal replacement therapy (CRRT) was used for metabolic acidosis of increasing severity. OUTCOMES: Despite the administration of vasopressors and other conservative therapies, the state of shock persisted, and metabolic acidosis did not improve even after CRRT. Ultimately, the patient died of multiple organ failure. LESSONS: For many poisonous wild plants, the precise profile of toxic compounds and mechanisms of action remain to be identified; when there is insufficient literature reporting on suspected plant poisoning, the medical personnel providing the treatment should consider the various side effects that differ from the reported ones and the possibility of more severe clinical progress and poor prognosis.

Crotalaria spectabilis poisoning in horses fed contaminating oats.

The present report describes the clinical and pathological changes induced by the consumption of oats contaminated with Crotalaria spectabilis seeds by horses. Eighty horses were exposed to oats containing 10 g/kg of C. spectabilis seeds with 0.46% pyrrolizidine alkaloids, and 21 horses died within a 6-month period. Clinical signs included jaundice, apathy, a hypotonic tongue, ataxia, hyporexia, weight loss, aimless wandering, violent behavior, and proprioceptive deficits. Pathological findings were predominant in the liver and included periportal bridging fibrosis, megalocytosis, centrilobular necrosis, and bile stasis. Other findings were Alzheimer's type II astrocytes in the cortex, midbrain, basal nuclei, brainstem and pons; multifocal edema and hemorrhage in the lungs; and degeneration and necrosis of the tubular epithelium of kidneys. Horses are highly sensitive to pyrrolizidine alkaloid-containing plants, and the observed clinical and pathological findings are typical of this poisoning. The seeds were planted, and botanical identification of the adult plants confirmed the diagnosis of C. spectabilis poisoning.

Clinical, pathologic, and toxicologic characterization of Salvia reflexa (lance-leaf sage) poisoning in cattle fed contaminated hay.

Salvia reflexa (lance-leaf sage)-contaminated alfalfa hay was fed to ~500 mixed-breed beef cattle. Within hours of exposure, nearly half of the cattle developed lethargy, anorexia, depression, and recumbency, followed by bellowing, colic, and death. Even though the uneaten contaminated hay was removed the first day, nearly 100 animals died within the first 48 h. Three of these cattle were examined postmortem, and tissues and hay samples were collected for microscopic and chemical analysis. Several days later, a smaller number of the clinically poisoned cattle developed neurologic disease with aberrant behavior, aggression, icterus, blindness, exhaustion, and death. A total of 165 cattle were fatally poisoned. Poisoned cattle had swollen, dark, mottled livers that had a prominent nutmeg-like lobular pattern on cut section. Histologically, there was severe centrilobular-to-panlobular hepatic necrosis with marked hepatocellular swelling, degeneration, and necrosis. The surviving cattle developed liver disease characterized by altered serum biochemical analyses and microscopic hepatocellular degeneration and necrosis. In subsequent biopsies and analysis, these lesions resolved within 6-7 mo. After confirming toxicity of the hay in cattle, goats, and mice, followed by a mouse bioassay-guided chemical fractionation process, Salvia reflexa was identified as the contaminant in the hay responsible for the hepatotoxicity. S. reflexa has not been reported previously to cause fatal hepatotoxicity in livestock in North America, to our knowledge.

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.

Identifying Plant Poisoning in Livestock in North America.

Poisonous plant intoxication is one of the first considerations for various livestock diseases and unexplained animal deaths. Although toxic plants commonly poison livestock, obtaining a definitive diagnosis is difficult and challenging. This article provides a framework to help livestock producers, veterinarians, and diagnosticians reach the most accurate and definitive diagnosis. For this discussion poisoning caused by plants containing dehydropyrrolizidine alkaloids is used to provide examples and suggestions for investigating and sampling. It is also used to show how to recruit expert collaborators, diagnostic resources, and information sources to amass required expertise, information, and laboratory results to produce the best diagnosis.

Palicourea marcgravii (Rubiaceae) poisoning in cattle grazing in Brazil.

Palicourea marcgravii is the most important poisonous plant of cattle in Brazil. It contains monofluoroacetic acid and causes sudden death associated with exercise. Herein, we describe the temporal and spatial distribution of the toxic disease. The survey was based on the epidemiological, clinical, and pathological data of the Setor de Anatomia Patológica (SAP) of the Universidade Federal Rural do Rio de Janeiro (UFRuralRJ) to report outbreaks of poisoning by P. marcgravii, from 1953 to 2018. Clinical signs were peracute and included labored breathing, loss of balance, muscle tremors, lateral recumbency, and limb paddling. Gross lesions such as congestion of large vessels and edema and pulmonary congestion were observed. Multifocal areas of vacuolar hydropic degeneration of distal contorted tubule cells with nuclear pyknosis were observed in the kidneys. The plant is found in forests, and the poisoning occurs mainly after clearing forests for pasture, in areas of natural forest recovery called "capoeira," which provide a favorable environment for maintaining P. marcgravii growth. Outbreaks of P. marcgravii poisoning coincided with periods of creation of large deforested pastures in the Southeast and Midwest regions of Brazil, and the poisoning should be considered an additional risk after deforestation. The most effective prophylaxis is fencing off the forest areas that contain these plants.

Fatal Yellow Oleander Poisoning Masquerading as Benign Candlenut Ingestion Taken for Weight Loss.

BACKGROUND: Candlenuts (Aleurites moluccana) and yellow oleander seeds (Thevetia peruviana) bear a physical resemblance to one another. Candlenuts are benign and marketed as weight loss supplements. Yellow oleander seeds, however, contain toxic cardioactive steroids; as few as 2 seeds may cause fatal poisoning. Because of their physical similarities, the potential for a lethal substitution exists. CASE REPORT: A 63-year-old woman presented to the emergency department with vomiting after ingesting 5 of what she believed to be candlenuts that were ordered online under the colloquial name "Nuez de la India" for the purpose of weight loss. She was bradycardic (nadir pulse of 30 beats/min) and hyperkalemic (serum potassium 7.3 mEq/L). Within hours of presentation she suffered a ventricular fibrillation arrest, followed by a terminal asystolic arrest. Postmortem analyses of liver tissue and the seeds were consistent with fatal T. peruviana poisoning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: T. peruviana seeds contain toxic cardioactive steroids; their physical resemblance to candlenuts poses a risk of potentially fatal substitution. Therapy with high-dose digoxin specific immune fragments (20-30 vials) may be helpful.

A volatolomic approach using cerumen as biofluid to diagnose bovine intoxication by Stryphnodendron rotundifolium.

An innovative volatolomic approach employs the detection of biomarkers present in cerumen (earwax) to identify cattle intoxication by Stryphnodendron rotundifolium Mart., Fabaceae (popularly known as barbatimão). S. rotundifolium is a poisonous plant with the toxic compound undefined and widely distributed throughout the Brazilian territory. Cerumen samples from cattle of two local Brazilian breeds ('Curraleiro Pé-Duro' and 'Pantaneiro') were collected during an experimental intoxication protocol and analyzed using headspace (HS)/GC-MS followed by multivariate analysis (genetic algorithm for a partial least squares, cluster analysis, and classification and regression trees). A total of 106 volatile organic metabolites were identified in the cerumen samples of bovines. The intoxication by S. rotundifolium influenced the cerumen volatolomic profile of the bovines throughout the intoxication protocol. In this way, it was possible to detect biomarkers for cattle intoxication. Among the biomarkers, 2-octyldecanol and 9-tetradecen-1-ol were able to discriminate all samples between intoxicated and nonintoxicated bovines. The cattle intoxication diagnosis by S. rotundifolium was accomplished by applying the cerumen analysis using HS/GC-MS, in an easy, accurate, and noninvasive way. Thus, the proposed bioanalytical chromatography protocol is a useful tool in veterinary applications to determine this kind of intoxication.

Identification of phytolaccosides in biological samples from pokeweed intoxication patients using liquid chromatography-tandem mass spectrometry.

In Phytolaccaceae family, Phytolacca americana L. (American pokeweed) and P. esculenta Van Houtte (Chinese pokeweed) are the two representative species among the genus. Pokeweeds have triterpenoid saponins as toxic compounds in every part of the plant. The saponins phytolaccoside A, B, D, E, and G were isolated from P. americana, and esculentoside H, J, L, K, M, I, and N were isolated from P. esculenta. Along with saponins, their aglycones (phytolaccagenin, phytolaccagenic acid, esculentic acid and jaligonic acid) were also isolated from P. americana and P. esculenta. Two people who unknowingly ate misidentified pokeweed plant roots were transferred to the emergency room. Urine and gastric content after irrigation were collected from the first patient (patient 1), and blood and urine were collected from the second patient (patient 2). The samples were analyzed to identify toxic substances with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the blood sample, 1.9 ng/mL of esculentoside A and 1.5 ng/mL of esculentoside C were detected, while the concentration of esculentoside B and H were below the LLOQ. In gastric contents and ingested roots, esculentoside A, B, C, and H were identified. Esculentoside A, C, and H were identified in the urine of patient 1, and esculentoside A and C were identified in the urine sample of patient 2. The developed analytical method was validated for parameters such as linearity, limit of detection, precision, accuracy, matrix effect, recovery, and process efficiency, and they showed clear and unbiased results.