Outbreak of Oleander (Nerium oleander) Poisoning in Dairy Cattle: Clinical and Food Safety Implications.

Oleander is a spontaneous shrub widely occurring in Mediterranean regions. Poisoning is sporadically reported in livestock, mainly due to the ingestion of leaves containing toxic cardiac glycosides (primarily oleandrin). In this study, 50 lactating Fleckvieh cows were affected after being offered a diet containing dry oleander pruning wastes accidentally mixed with fodder. Clinical examination, electrocardiogram, and blood sampling were conducted. Dead animals were necropsied, and heart, liver, kidney, spleen, and intestine were submitted to histological investigation. Oleandrin detection was performed through ultra-high performance liquid chromatography-tandem mass spectrometry in blood, serum, liver, heart, milk, and cheese samples. Severe depression, anorexia, ruminal atony, diarrhea, serous nasal discharge, tachycardia, and irregular heartbeat were the most common clinical signs. The first animal died within 48 h, and a total of 13 cows died in 4 days. Disseminated hyperemia and hemorrhages, multifocal coagulative necrosis of the cardiac muscle fibers, and severe and diffuse enteritis were suggestive of oleander poisoning. The diagnosis was confirmed by the presence of oleandrin in serum, liver, heart, milk, and cheese. Our results confirm the high toxicity of oleander in cattle and report for the first time the transfer into milk and dairy products, suggesting a potential risk for the consumers.

Cardiac arrhythmias, electrolyte abnormalities and serum cardiac glycoside concentrations in yellow oleander (Cascabela thevetia) poisoning - a prospective study.

BACKGROUND: Consumption of yellow oleander (Cascabela thevetia) is a popular method of intentional self-harm in South India. OBJECTIVES: The objectives of this study were to identify the cardiac arrhythmias and electrolyte abnormalities in yellow oleander poisoning and to identify the association between electrolyte abnormalities, cardiac glycoside concentrations at admission and the severity of cardiotoxicity. This study was also designed to identify clinical and biochemical parameters at presentation which predict serious arrhythmias and determinants of mortality. MATERIALS AND METHODS: This was a prospective study among 192 patients who attended our Emergency department after consuming yellow oleander seeds. Patients were monitored with serial ECGs. Serious cardiac arrhythmias included sinus bradycardia <40/min, sinus arrest/exit block, second or third degree AV block, atrial tachyarrhythmias and ventricular tachyarrhythmias. Serum sodium, potassium, magnesium, total calcium and cardiac glycoside concentrations were measured at presentation for all 192 patients. Serial estimation of cardiac glycoside concentration was done in 43 patients who presented within 24 hours of consuming at least five seeds. RESULTS: At presentation, 46 patients had serious arrhythmias and on follow-up, 11 developed new-onset serious arrhythmia. Sinus bradycardia (27%) was the most common arrhythmia followed by second-degree AV block (17%); multiple arrhythmias were observed in 18%. Digoxin effect in ECG correlated significantly with hyperkalemia. Mortality rate was 5%. Serum sodium, total calcium and magnesium levels did not correlate with cardiotoxicity. Cardiac glycoside concentration was of relatively modest clinical utility to discriminate patients with serious dysrhythmias (AUC: 0.719, 95% CI: 0.63-0.81). Prolonged PR interval and digoxin effect in ECG were significantly associated with an increased likelihood of serious dysrhythmias. Increase in 0.4 number of seed intake increased the odds of mortality by 1.5 times when all other independent variables were kept constant. CONCLUSION: Cardiac glycoside concentration at the time of presentation predicted the development of new-onset serious arrhythmias. Although serum potassium correlated significantly with cardiac glycoside concentration at admission and overall serious dysrhythmias, it did not predict the development of new-onset serious arrhythmia. On the whole, serious dysrhythmias were significantly associated with higher number of seeds ingested, hypotension at admission, PR interval prolongation, presence of digoxin effect in ECG, hyperkalemia and higher cardiac glycoside concentration. The independent determinants of mortality were larger number of seeds ingested and hypotension at admission. Cardiac glycoside concentration and hyperkalemia failed to be independent markers of serious dysrhythmias as well as mortality.

Recurrent Ventricular Arrhythmia Caused by Ingestion of Aconitum (Monkshood) Flowers.

We report the case of a patient who presented with respiratory failure, recurrent ventricular fibrillation, ventricular arrhythmias, and hypotension after an intentional ingestion of aconite flowers. Significant ingestion of this plant can produce life-threatening cardio- and neurotoxicity that may require evacuation from the wilderness to a medical facility capable of advanced treatment and intensive care monitoring.

Hypoglycin A Content in Blood and Urine Discriminates Horses with Atypical Myopathy from Clinically Normal Horses Grazing on the Same Pasture.

Hypoglycin A (HGA) in seeds of Acer spp. is suspected to cause seasonal pasture myopathy in North America and equine atypical myopathy (AM) in Europe, fatal diseases in horses on pasture. In previous studies, this suspicion was substantiated by the correlation of seed HGA content with the concentrations of toxic metabolites in urine and serum (MCPA-conjugates) of affected horses. However, seed sampling was conducted after rather than during an outbreak of the disease. The aim of this study was to further confirm the causality between HGA occurrence and disease outbreak by seed sampling during an outbreak and the determination of i) HGA in seeds and of ii) HGA and MCPA-conjugates in urine and serum of diseased horses. Furthermore, cograzing healthy horses, which were present on AM affected pastures, were also investigated. AM-pastures in Germany were visited to identify seeds of Acer pseudoplatanus and serum (n = 8) as well as urine (n = 6) from a total of 16 diseased horses were analyzed for amino acid composition by LC-ESI-MS/MS, with a special focus on the content of HGA. Additionally, the content of its toxic metabolite was measured in its conjugated form in body fluids (UPLC-MS/MS). The seeds contained 1.7-319.8 µg HGA/g seed. The content of HGA in serum of affected horses ranged from 387.8-8493.8 µg/L (controls < 10 µg/L), and in urine from 143.8-926.4 µg/L (controls < 10 µg/L), respectively. Healthy cograzing horses on AM-pastures showed higher serum (108.8 ± 83.76 µg/L) and urine concentrations (26.9 ± 7.39 µg/L) compared to control horses, but lower concentrations compared to diseased horses. The range of MCPA-carnitine and creatinine concentrations found in diseased horses in serum and urine were 0.17-0.65 mmol/L (controls < 0.01), and 0.34-2.05 µmol/mmoL (controls < 0.001), respectively. MCPA-glycine levels in urine of cograzing horses were higher compared to controls. Thus, the causal link between HGA intoxication and disease outbreak could be further substantiated, and the early detection of HGA in cograzing horses, which are clinically normal, might be a promising step in prophylaxis.

Hypoglycemia associated with oleander toxicity in a dog.

Oleander poisoning typically results in cardiac arrhythmias, hyperkalemia, and gastrointestinal irritation, and can be fatal. Oleander extracts have also been studied experimentally as hypoglycemic agents. Here, we describe a dog with confirmed oleander toxicosis presenting with classical symptoms and also hypoglycemia. After excluding other likely causes of hypoglycemia, the finding was attributed to oleander toxicosis, which has not been previously reported in dogs. A 7-year-old female spayed Maltese was presented to the emergency service after ingesting oleander leaves. Toxicosis was confirmed by measurement of digoxin using a competitive binding immunoassay, patient level 0.7 ng/mL (0.9 nmol/L) 24-h post-ingestion. Clinical symptoms included vomiting, cardiac arrhythmia, mild hyperkalemia, and hypoglycemia. Treatment was successful with aggressive supportive care, and the dog was discharged from the hospital after 48 h and made a full recovery. This case reviews the presentation and treatment of oleander toxicity but also highlights possible effects of oleander on blood sugar in dogs. Hypoglycemia in this dog, attributed to oleander poisoning, is interesting as it supports experimental research into hypoglycemic properties of oleander extracts.

A validated method for quantifying atractyloside and carboxyatractyloside in blood by HPLC-HRMS/MS, a non-fatal case of intoxication with Atractylis gummifera L.

Atractyloside (ATR) and carboxyatractyloside (CATR) are diterpene glycosides that are responsible for the toxicity of several Asteraceae plants around the world. Mediterranean gum thistle (Atractylis gummifera L.) and Zulu impila (Callilepis laureola DC.), in particular, are notoriously poisonous and the cause of many accidental deaths, some suicides and even some murders. There is no current method for measuring the two toxins in biological samples that meet the criteria of specificity required in forensic medicine. We have endeavored to fill this analytical gap. Analysis was carried out using a solid-phase extraction and a high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry detection. The method was validated in the whole blood with quantification limits of 0.17 and 0.15 µg/L for ATR and CATR, respectively. The method was applied to a non-fatal case of intoxication with A. gummifera. To the best of the authors' knowledge, this is the first time that a concentration of ATR and CATR in blood (883.1 and 119.0 µg/L, respectively) and urine (230.4 and 140.3 µg/L, respectively) is reported. ATR and CATR were quantified in A. gummifera roots by the standard method addition (3.7 and 5.4 mg/g, respectively).

Rapid detection of convallatoxin using five digoxin immunoassays.

CONTEXT: Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detecting foxglove and oleander ingestion has been demonstrated, but no studies have evaluated the structurally similar convallatoxin found in Convallaria majalis (lily of the valley) for rapid laboratory screening, nor has digoxin immune Fab been tested as an antidote for this ingestion. OBJECTIVE: We aimed to (1) evaluate multiple digoxin assays for cross-reactivity to convallatoxin, (2) identify whether convallatoxin could be detected in vivo at clinically significant doses, and (3) determine whether digoxin immune Fab could be an effective antidote to convallatoxin. MATERIALS AND METHODS: Cross-reactivities of purified convallatoxin and oleandrin with five common digoxin immunoassays were determined. Serum from mice challenged with convallatoxin was tested for apparent digoxin levels. Binding of convallatoxin to digoxin immune Fab was determined in vitro. RESULTS: Both convallatoxin and oleandrin were detectable by a panel of commonly used digoxin immunoassays, but cross-reactivity was variable between individual assays. We observed measurable apparent digoxin levels in serum of convallatoxin intoxicated mice at sublethal doses. Convallatoxin demonstrated no binding by digoxin immune Fab. CONCLUSION: Multiple digoxin immunoassays detect botanical cardiac glycosides including convallatoxin and thus may be useful for rapid determination of severe exposures, but neutralization of convallatoxin by digoxin immune Fab is unlikely to provide therapeutic benefit.