Veratrum parviflorum poisoning: identification of steroidal alkaloids in patient blood and breast milk.

INTRODUCTION: The Veratrum genus is composed of plants containing a diverse set of steroidal alkaloids. Veratrum plant material has been utilized for centuries as herbal medicines, however the alkaloids have such a low therapeutic index that they are not used in modern medicine. Here we report an incident of inadvertent ingestion of V. parviflorum by hikers in Georgia that allowed detection, and in several instances identification of alkaloids from the plant, and correlated their presence within patient blood and breast milk specimens. CASE HISTORY: Eight patients, three male and five female, presented in the spring of 2020 and 2021 with symptoms requiring emergent medical attention after ingestion of Veratrum parviflorum. All patients believed the plants to be a local native species of wild leek, Allium tricoccum, locally known as ramps. Plants were identified using photographs as well as fresh and cooked plant material provided by patients, in consultation with botanists at the University of Georgia Herbarium. Written consent was obtained from all patients for collection of blood and breast milk specimens for laboratory identification of Veratrum alkaloids. METHODS: V. parviflorum plant material, and patient serum and breast milk were analyzed by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) to identify steroidal alkaloids. RESULTS: The V. parviflorum extract was confirmed to contain cyclopamine, veratramine, jervine, and muldamine. Two out of the eight patients had detectable concentrations of Veratrum alkaloids. Of the alkaloids identified in the plant, cyclopamine and jervine were detected within patient serum, and cyclopamine and veratramine were observed to be present in breast milk. DISCUSSION: Toxicity resulting from Veratrum steroidal alkaloids has primarily been reported from V. album and V. viride. This is the second report of V. parviflorum poisoning. The present work reports for the first time the presence of muldamine and jervine within V. parviflorum. This work provides the first instance of identification of Veratrum alkaloids in breast milk. Thus, the findings presented herein add to literature record causative agents contributing to the toxicity of V. parviflorum when ingested and potential for secondary poisoning through breastfeeding. CONCLUSION: V. parviflorum toxicity was observed to cause nausea, vomiting, hypotension, bradycardia, abdominal pain, light-headedness, blurred vision, and tingling in the arms. Patients experiencing mild symptoms improved with supportive care, IV fluids, and antiemetics, but hemodynamically unstable patients required atropine and vasopressors. This study demonstrated that more lipophilic Veratrum alkaloids can be passed along in breast milk, which suggests additional precautions may be critical to limit further poisonings.

A suicide attempt by ingestion of oleander leaves and treatment with digoxin-specific Fab antibody fragments.

Natural cardiac glycosides have positive inotropic heart effects but at high, toxic doses they can cause life-threatening cardiac arrhythmias. Here we present the first Croatian case of a 16-year-old girl who attempted suicide by eating dried oleander leaves, which contain natural cardiac glycosides, and her treatment with a specific antidote. The girl presented with an oedema of the uvula indicating local toxicity, severe bradycardia, first-degree atrioventricular block, drowsiness, and vomiting. Having taken her medical history, we started treatment with atropine, intravenous infusion of dextrose-saline solution and gastroprotection, but it was not successful. Then we introduced digoxin-specific Fab antibody fragments and within two hours, the patient's sinus rhythm returned to normal. Cases of self-poisoning with this oleander are common in South-East Asia, because it is often used as a medicinal herb, and digoxin-specific Fab fragments have already been reported as effective antidote against oleander poisoning there. Our case has taught us that it is important to have this drug in the hospital pharmacy both for digitalis and oleander poisoning.

Datura and Brugmansia plants related antimuscarinic toxicity: an analysis of poisoning cases reported to the Taiwan poison control center.

INTRODUCTION: Datura and Brugmansia plants, especially Datura species, have been used for their hallucinogenic effects in the United States and Europe; whereas Datura plants have been used as a traditional medicine in many Asian countries. This study was conducted to better understand the pattern and outcome of Datura/Brugmansia plant related poisoning in Taiwan. METHODS: This is a retrospective case series study of all cases with Datura/Brugmansia exposure reported to the Taiwan Poison Control Center between 1986 and 2015. Data for patients with relevant poisoning were reviewed and abstracted. Logistic regression analysis was used to identify potential predictors of the severity of poisoning; bivariate analysis was employed to assess the effectiveness of physostigmine in the treatment of Datura/Brugmansia poisoning. RESULTS: A total of 203 cases involving 114 Datura exposures and 89 Brugmansia suaveolens exposures were eligible for analysis. Using Datura/Brugmansia for a medicinal purpose by the patients without consulting Chinese medicine practitioners was the most common reason of poisoning (81.2%); whereas only 2% of the patients were poisoned after medicinal use associated with the prescription from Chinese medicine practitioners. None of the 203 patients had used Datura/Brugmansia plant for recreational purpose. Most frequently observed clinical effect was mydriasis (53.2%), followed by confusion (40%), tachycardia (35.5%), dry mouth (35.5%), dizziness (34%), dry skin (32.5%), and delirium (31%). Seventy-three cases (36%) had severe effects; none of them died. Misidentification of the plants and ingestion of plant parts other than flowers were positively associated with the severity of poisoning. Forty patients (19.7%) received physostigmine therapy and patients receiving physostigmine had an earlier resolution of central nervous system toxicity than those who did not. CONCLUSIONS: Medicinal use without consulting Chinese medicine practitioners is the main reason for Datura/Brugmansia poisoning in Taiwan. Consumption of parts other than flowers and misidentification of the plants predicted the severity of poisoning in this study. Patients who received physostigmine appear to have earlier improvement in the central nervous system effects. No adverse events were reported from physostigmine administration.

Hikers poisoned: Veratrum steroidal alkaloid toxicity following ingestion of foraged Veratrum parviflorum.

INTRODUCTION: Steroidal alkaloids are found in plants of the genus Veratrum. Their toxicity manifests as gastrointestinal symptoms followed by a Bezold-Jarisch reflex: hypopnea, hypotension, and bradycardia. Some Veratrum steroidal alkaloids are also teratogens interfering with the hedgehog-2 signaling pathway, which causes cyclopsia and holoprosencephaly. We present a case of accidental poisoning from Veratrum parviflorum mistaken for the edible Allium tricoccum (ramps, wild leek). CASE HISTORY: A 27-year-old man and his 25-year-old wife presented to the emergency department with nausea, vomiting, hypotension, and bradycardia after foraging and ingesting plants that they believed to be a local native species of wild leek. METHODS: We collected and analyzed the implicated fresh plant material and both patients' serum/plasma. We used liquid chromatography-mass spectroscopy and high-resolution electrospray ionization time of flight tandem mass spectrometry to extract and characterize steroidal alkaloids from the foraged plant and patients' serum. RESULTS: Our V. parviflorum samples contained verazine, veratramine, veratridine, and cyclopamine. DISCUSSION: Steroidal alkaloids have been previously isolated from Veratrum viride and Veratrum album and toxicity has been reported mainly from V. album species. CONCLUSION: V. parviflorum toxicity manifests with gastrointestinal and cardiac symptoms. Treatment is symptomatic and supportive as with previous case reports of toxicity with other Veratrum species.

Datura fruit poisoning.

Datura plants contain anticholinergic properties. Consumers may present with a spectrum of anticholinergic symptoms, including hallucination, agitation, tachycardia, delirium, hyperthermia, and dilated pupils. Prompt identification of the symptoms with appropriate treatment can be life-saving. Some patients might not be able to provide history and therefore recognition of toxidromes is imperative. Awareness should be built among the public who may be exposed to such fruits or plants.

[Acute Monkshood Intoxication Requiring Acute Resuscitation in Suicidal Intent]. / Reanimationspflichtige akute Eisenhutintoxikation in suizidaler Absicht.

We report about an acute monkshood intoxication requiring acute resuscitation in suicidal intent in a 56-year-old patient. The Blue Monkshood (Aconitum napellus) is considered to be the most toxic plant in Europe. All plant parts contain the highly toxic alkonoid aconitin. The lethal dose in adults is 2 - 6 mg. Intoxications are often fatal. Asymptomatic patients with suspected monkshood intoxication should also be monitored on an ICU. First signs of intoxication are paraesthesia in the mouth and throat area, abdominal cramps, nausea, vomiting and severe pain in skeletal muscle. Affected patients die within hours after ingestion due to respiratory distress and/or cardiac arrhythmia.The most important measure after oral ingestion is to achieve a rapid primary poison elimination clearance (in the case of awareness clear patients, trigger vomiting, otherwise gastric lavage under protective intubation) and the subsequent carbonation. A specific antidote is not available. The management of an intoxication consists primarily of the therapy of the rhythm disturbances in the form of magnesium and amiodarone.Strict adherence to protective measures (gloves, masks) must be strictly observed. A direct skin contact with plant parts is to be avoided as well as the potential contact with vomit or aspirate.

Successful use of digoxin-specific immune Fab in the treatment of severe Nerium oleander toxicosis in a dog.

OBJECTIVE: To describe a case in which digoxin-specific immune Fab was used successfully in a dog with severe oleander toxicosis secondary to ingesting plant material. CASE SUMMARY: A 6-year-old intact female Rhodesian Ridgeback mixed breed dog was presented for severe oleander toxicosis and was refractory to all antiarrhythmic therapies and supportive care. Digoxin-specific immune Fab was successful in treating this dog. The dog recovered but suffered ischemic injuries, the long-term effects of which are unknown. NEW OR UNIQUE INFORMATION PROVIDED: This report describes the successful use of digoxin-specific immune Fab in the treatment of oleander toxicosis in a dog, which has not previously been published in veterinary literature. Oleander poisoning can be associated with permanent cardiac arrhythmias due to the ischemic damage.

Earwax: A clue to discover fluoroacetate intoxication in cattle.

An innovative method was developed to detect fluoroacetate poisoning in cattle by headspace/gas chromatographic analysis of earwax samples of intoxicated cattle. Samples were collected from 2 groups of cattle subjected to induced fluoroacetate intoxication, each group receiving a different dose of acetamide (antidote). Monofluoroacetic acid was detected in samples of intoxicated cattle in concentrations inversely proportional to the dose of acetamide. Thus, earwax analysis represents a successful approach for detection and monitoring of fluoroacetate poisoning.

Evaluation of processed borax as antidote for aconite poisoning.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconite root is very poisonous; causes cardiac arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is mentioned for management of aconite poisoning. AIM OF THE STUDY: The investigation evaluated antidotal effect of processed borax against acute and sub-acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw aconite. MATERIALS AND METHODS: For acute protection Study, single dose of toxicant (35mg/kg) and test drug (22.5mg/kg and 112.5mg/kg) was administered orally, and then 24h survival of animals was observed. The schedule was continued for 30 days in sub-acute protection Study with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg and 112.5mg/kg) and vehicle. Hematological and biochemical tests of blood and serum, histopathology of vital organs were carried out. The cardiac activity Study was continued for 30 days with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg), processed borax solution (22.5mg/kg) and vehicle; ECG was taken after 1h of drug administration on 1TB, 15th and on 30th day. For neuro-muscular activity Study, the leech dorsal muscle response to 2.5µg of acetylcholine followed by response of toxicant at 25µg and 50µg doses and then response of test drug at 25µg dose were recorded. RESULTS: Protection index indicates that treated borax gave protection to 50% rats exposed to the lethal dose of toxicant in acute protection Study. Most of the changes in hematological, biochemical parameters and histopathological Study induced by the toxicant in sub-acute protection Study were reversed significantly by the test drug treatment. The ventricular premature beat and ventricular tachyarrhythmia caused by the toxicant were reversed by the test drug indicate reversal of toxicant induced cardio-toxicity. The acetylcholine induced contractions in leech muscle were inhibited by toxicant and it was reversed by test drug treatment. CONCLUSION: The processed borax solution is found as an effective protective agent to acute and sub-acute aconite poisoning, and aconite induced cardiac and neuro-muscular toxicity. Processed borax at therapeutic dose (22.5mg/kg) has shown better antidotal activity profile than five times more than therapeutic dose (112.5mg/kg).

Activated charcoal significantly reduces the amount of colchicine released from Gloriosa superba in simulated gastric and intestinal media.

BACKGROUND: Poisoning with Gloriosa superba, a plant containing colchicine, is common in Sri Lanka. OBJECTIVES: This study was to estimate release of colchicine from 5 g of different parts of Gloriosa superba in simulated gastric and intestinal media, and examine the binding efficacy of activated charcoal (AC) to colchicine within this model. METHODS: A USP dissolution apparatus-II was used to prepare samples for analysis of colchicine using HPLC. RESULTS: Cumulative colchicine release from tuber in gastric media at 120 minutes was significantly higher (2883 µg/g) than in intestinal media (1015 µg/g) (p < .001). Mean ± SD cumulative colchicine concentration over 2 hours from tuber, leaves and trunk in gastric medium was 2883.15 ± 1295.63, 578.25 ± 366.26 and 345.60 ± 200.08 µg/g respectively and the release in intestinal media was 1014.75 ± 268.16, 347.40 ± 262.61 and 251.55 ± 285.72 µg/g respectively. Introduction of 50 g of AC into both media made colchicine undetectable (<0.1 µg/ml). CONCLUSIONS: The tuber released the highest quantity of colchicine. The colchicine release and elapse time to achieve saturated, equilibrium dissolution mainly depends on physicochemical properties of plant part. Significant in vitro binding of colchicine to AC suggests that AC has a role in decontamination of patients presenting to hospital after ingestion of Gloriosa superba.

Comfrey herbal remedy causing second-degree heart block: do not be outfoxed by digitalis.

A previously well woman aged 63 years presents to the emergency department with vomiting, palpitations and 3 presyncopal episodes. She had no previous medical or cardiac history, with the patient stating that she tried a herbal remedy of boiled comfrey leaves for insomnia 18 hours before arrival to the department. Her ECG showed multiple abnormalities, including bradycardia, second-degree atrioventricular node block, Mobitz Type 2, a shortened QT interval, downsloping ST depression and presence of U waves. After viewing the images of comfrey and foxglove, it highlighted the possibility of mistaken ingestion of Digitalis, containing the organic forms of cardiac glycosides, such as digoxin and digitoxin. Raised serum digoxin levels confirmed this. The patient was haemodynamically stable, and given digoxin-binding antibodies. After 5 days of cardiac monitoring, her ECG returned to normal rhythm, and she was discharged home.

Antitoxic effect of Veratrilla baillonii on the acute toxicity in mice induced by Aconitum brachypodum, one of the genus Aconitum.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum brachypodum Diels (Family Ranunculaceae) is well known for both its good therapy and high toxicity in Yunnan and Sichuan provinces in China. Noticeably, Veratrilla baillonii Franch (Family Gentianaceae), an ethnodrug used by Naxi and Lisu nationalities in Yunnan Province, has been widely considered to possess antitoxic effects on Aconitum plants in herbal therapy and folklore medicines. MATERIALS AND METHODS: The present study was conducted to determine the detoxic activities of the water decoction of Veratrilla baillonii Franch (WVBF) on the the chloroform fraction of Aconitum brachypodum Diels (CFA) induced acute toxicity in mice. The physiological (symptoms, body weight, etc.) as well as pathological and clinical biochemistry parameters were assessed and used as the markers for the toxicity. (1)H nuclear magnetic resonance (NMR) based metabolic approach was adopted to further discuss the mechanism. RESULTS: The acute poisoning effects of CFA on mice were observed at doses of 20-62.5mgkg(-1), resulting in an oral median lethal dose (LD50) of 41.3mgkg(-1). Histologically, distinct degenerative changes of the heart, liver and kidney were observed. The biochemistry parameters in the serum as well as metabolites in heart and brain were also altered. However, WVBF (25-200mg/kg) attenuated all the acute toxicity and pathological changes, properly regulated the biochemistry parameters, and reversed the concentration alterations for some metabolites in the heart and brain of mice induced by 40mg/kg of CFA to a certain extent. CONCLUSIONS: WVBF significantly reduced the onset of the CFA toxicity. This study may contribute to further understanding of the toxicological and pharmacological profiles of Aconitum brachypodum and the detoxic property of Veratrilla baillonii.

Successful treatment of Solanum dulcamara intoxication in a Labrador retriever puppy.

A 10-week-old intact male Labrador retriever dog was presented for acute onset of weakness, ataxia, and generalized muscle tremors. The puppy was suffering respiratory and central nervous system (CNS) depression, was mildly pyrexic, and vomited plant material that was identified as creeping nightshade (Solanum dulcamara). He responded well to supportive care and was discharged successfully. To the authors' knowledge, this is the first report of Solanum dulcamara toxicity occurring in a dog.

Traitement réussi d'une intoxication parSolanum dulcamarachez un chiot Labrador retriever. Un chien Labrador retriever mâle intact âgé de 10 semaines a été présenté pour l'apparition aiguë de faiblesse, d'ataxie et des tremblements musculaires généralisés. Le chiot souffrait d'une dépression du système respiratoire et du système nerveux central (SNC), présentait une pyrexie légère et vomissait du matériau végétal qui a été identifié comme étant de la morelle douce-amère (Solanum dulcamara). Il a bien répondu à des soins de soutien et a reçu un congé pour un traitement réussi. À la connaissance des auteurs, c'est le premier rapport d'une toxicité de Solanum dulcamara se produisant chez un chien.(Traduit par Isabelle Vallières).

Lathyrus hirsutus (Caley Pea) intoxication in a herd of horses.

BACKGROUND: Caley Pea (Lathyrus hirsutus) is potentially toxic to horses, but large case series are not reported. OBJECTIVES: To describe the clinical signs of horses intoxicated with Lathyrus hirsutus and speculate on the neuroanatomical lesion localization and pathogenesis based upon the observed clinical signs. ANIMALS: Twenty-two of 25 horses ranging in age from 6 to 34 months were affected. Five affected horses were presented to the OSUCHVS for evaluation and treatment after having been attended at the ranch by a local veterinarian (ALA). An additional horse that had been euthanized was also presented for necropsy. METHODS: A case series is presented. Diagnostic evaluation included: physical examination, complete blood count, serum biochemistry, CSF analysis, EMG, ERG, upper airway endoscopy, muscle biopsy, and serum vitamin E analysis. The grain ration consumed by the affected horses was analyzed for ionophores and cultured for fungi: the hay was examined for toxic plants. RESULTS: Bermuda grass hay consumed by the horses contained large quantities of mature Lathyrus hirsutus. Acute clinical signs conform to earlier descriptions of Lathyrus hirsutus intoxication in cattle. Residual neurologic signs were characterized by incoordination in the rhythmicity of multiple gaits. Evidence of mild neurogenic muscle atrophy was recognized in 1 of 5 horses biopsied. CONCLUSIONS AND CLINICAL IMPORTANCE: Caley Pea intoxication may occur within days of seed pod consumption. The neurologic signs are unique and suggest involvement of the upper motor neuron system and regions of the spinal cord influencing voluntary motor movement. Drought conditions during plant growth may increase the risk of toxicosis.

Treatment of pieris ingestion in goats with intravenous lipid emulsion.

Seven goats and one ram presented with clinical signs including regurgitation, obtundation, anorexia, apparent pain, and bloat. The animals had escaped from their barn, and it was discovered that they had ingested leaves of Pieris japonica, Japanese pieris, a grayanotoxin-containing plant. Animals were treated with antibiotics, calcium borogluconate, B vitamins, and activated charcoal within the first 24-h postexposure, which was followed by the recovery of the ram and two goats and the death of two goats. Approximately 36 h after Japanese pieris ingestion, one of the three remaining anorectic goats was dosed with intravenous lipid emulsion (ILE). This goat recovered within a few hours. The remaining two goats were given ILE the next day and appeared to recover, but one died a week later of aspiration pneumonia.

Eating seeds from the 'be still' tree, yet having lucky nut poisoning: a case of acute yellow oleander poisoning.

A 25-year-old woman was evaluated and treated for ingestion of Thevetia peruviana seeds and flower petals-a natural digoxin cross reacting cardinolide-with intent to cause self-harm. The following case report provides the clinical presentation, treatment and management of acute yellow oleander poisoning.

Mutagenicity and cytotoxicity of liquid waste, press water and pond water, produced in the cassava flour industry, and of antitoxic sodium thiosulfate.

BACKGROUND: Cassava (Manihot esculenta Crantz), a plant used as food and an ingredient in industry, contains cyanogenic glycosides. The cassava root contains wastewater, popularly known as manipueira, which is a toxic substance. Its ingestion by animals causes poisoning although they react positively to treatment with sodium thiosulfate. The present research evaluates the cytotoxicity and the mutagenicity of liquid waste produced in the process of industrialization of the bitter cassava, olho-junto variety. The liquid wastes are characterized as press water, which is obtained when the cassava roots are pressed; pond water, which is press water stored in impounded ponds; and a solution of sodium thiosulfate, pure and with other waste. RESULTS: The system tests comprised root meristematic cells of Allium cepa L. and bone marrow cells of Rattus norvegicus. Treatment with saline solution was cytotoxic for Allium cepa L. and significantly reduced cell division rate. Although no treatment was cytotoxic in any of the tests with rats, the thiosulfate solution was clastogenic for the chromosomal aberrations test. CONCLUSION: Since it is harmful to the genetic material submitted within the conditions of current research, sodium thiosulfate should only be used in emergency conditions in which the benefits exceed the risks.