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.

A toxic shrub turned therapeutic: The dichotomy of Nerium oleander bioactivities.

Nerium oleander L. is a medicinal plant, used for the treatment of cancers and hyperglycemia across the world, especially in Indian sub-continent, Turkey, Morocco, and China. Although clinical studies supporting its pharmacological effects remain critically underexplored, accidental and intentional consumption of any part of the plant causes fatal toxicity in animals and humans. While the polyphenolic fraction of oleander leaves has been attributed to its pre-clinical pharmacological activities, the presence of diverse cardiac glycosides (especially oleandrin) causes apoptosis to cancer cells in vitro and results in clinical signs of oleander poisoning. Thus, the dual pharmacological and toxicological role of oleander is a perplexing dichotomy in phytotherapy. The current investigative review, therefore, intended to analyze the intrinsic and extrinsic factors that likely contribute to this conundrum. Especially by focusing on gut microbial diversity, abundance, and metabolic functions, oleander-associated pharmacological and toxicological studies have been critically analyzed to define the dual effects of oleander. Electronic databases were extensively screened for relevant research articles (including pre-clinical and clinical) related to oleander bioactivities and toxicity. Taxonomic preference was given to the plant N. oleander L. and synonymous plants as per 'The World Flora Online' database (WCSP record #135196). Discussion on yellow oleander (Cascabela thevetia (L.) Lippold) has intentionally been avoided since it is a different plant. The review indicates that the gut microbiota likely plays a key role in differentially modulating the pharmacological and toxicological effects of oleander. Other factors identified influencing the oleander bioactivities include dose and mode of treatment, cardiac glycoside pharmacokinetics, host-endogenous glycosides, plant material processing and phytochemical extraction methods, plant genotypic variations, environmental effects on the phytochemical quality and quantity, gene expression variations, host dietary patterns and co-morbidity, etc. The arguments proposed are also relevant to other medicinal plants containing toxic cardiac glycosides.

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.

Poisonous delicacy: Market-oriented surveys of the consumption of Rhododendron flowers in Yunnan, China.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants from the family Ericaceae, and in particular those in the genus Rhododendron are frequently reported to contain grayanotoxins. Plant products such as honey and herbal medicines made from these plants occasionally contain grayanotoxins, and in turn may lead to intoxication. The balance between the benefits and risk of poisoning from Rhododendrons is of concerns. This study explores the ethnobotanical knowledge of the people in Yunnan, China as regards the consumption of Rhododendron flowers, and gives special focus to their assessment of the benefit-risk balance. MATERIALS AND METHODS: An ethnobotanical survey was conducted across 14 county-level local markets in north and central Yunnan province, during which a total of 82 stalls selling Rhododendron flowers were visited and 204 people were interviewed. Voucher specimens were obtained under the guidance of collectors, and details about local practices and knowledge were recorded using semi-structured interviews and participatory observations. RESULTS: The consumption of the corollas of Rhododendron decorum Franch. Flowers (RDf) or Rhododendron pachypodum Balf. f. & W.W. Sm. Flowers (RPf) as a seasonal delicacy is a long-standing tradition in the study area. RDf are widely consumed in northwest and northeast Yunnan, while RPf are more prevalent in the central regions of Yunnan, and there is a high consistency in the knowledge of the process for detoxification or palatability for each species. The main reasons for eating the flowers were listed as health benefits (mostly clear heat), wild collected, tradition and good flavor. All RPf consumers stated that the corolla from this species is not toxic, while 67.4% of the RDf consumers claim that the corolla from RDf is toxic. We compared the two species and analyzed their process intensities, poisoning cases and cautions, market trade forms and existing toxicity studies, which agreed well and consistently that the corolla of RDf deserve more toxicity attention than RPf. CONCLUSION: Our study provides a window to look into the ways, beyond honey and herbal medicine, by which Rhododendron species have influenced human wellbeing. The local culture can justify eating Rhododendron flowers, and meanwhile, has developed a series of skills to avoid the side effects of eating them, and therefore the study also provides a good case to answer more general questions about the rationality of eating any plant products by assessing the trade-off between benefits and side effects.

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.

Toxicity of Crepis lacera in grazing ruminants.

BACKGROUND: Crepis lacera is a plant from the Asteraceae family that is common in the Mediterranean region. Farmers believe that this plant may be deadly to small ruminants in areas of southern Italy. However, scientific evidence is lacking, and no proof exists that C. lacera is toxic to ruminants. Necropsies conducted on four sheep revealed lesions in their livers and kidneys. RESULTS: In the current study, we described sheep poisoning and isolated secondary metabolites from Crepis lacera to assess the metabolites' biological activity both in vitro and in vivo. Phytochemical study of the aerial portions of Crepis lacera led to the isolation of five sesquiterpene lactones and two phenolic compounds. Cellular viability was evaluated in cell cultures of the bovine kidney cell line Madin Darby Bovine Kidney (MDBK) after incubation with phytochemicals. Our results showed that three sesquiterpene lactones, 8-epidesacylcynaropicrin-3-O-ß-glucopyranoside (2), 8-epigrosheimin (3), and 8-ß-hydroxydehydrozaluzanin C (4), were cytotoxic after 48 h of incubation. In addition, in the in vivo study, animals that received 1 mg/kg body weight (bw) of Crepis lacera extract and were then sacrificed after 48 h showed significant lesions in their liver, lungs and kidneys. These lesions were also found in rats that received 2 mg/kg bw of the same extract and sacrificed after 24 and 48 h. CONCLUSIONS: These results validate the hypothesis that C. lacera is potentially dangerous when ingested in large quantities by grazing small domestic ruminants. Further studies are necessary to clarify the molecular mechanisms of Crepis spp. toxicity in animals.

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.

Suicide attempt with self-made Taxus baccata leaf capsules: survival following the application of extracorporeal membrane oxygenation for ventricular arrythmia and refractory cardiogenic shock.

CONTEXT: Yew intoxication has been known for many years; high dose ingestion of Taxus baccata leads to cardiac toxicity mediated by calcium and sodium channel blocking properties. We present a case report of a patient who attempted suicide after T. baccata ingestion, causing refractory cardiogenic shock requiring temporary circulatory assistance by veno-arterial extra corporeal membrane oxygenation (VA ECMO). CASE DETAILS: A 28-year-old man was admitted to the critical care unit of a university hospital for arrhythmia after ingestion of self-made T. baccata leaf capsules. He rapidly developed cardiovascular collapse requiring mechanical ventilation, high dose intravenous catecholamines and electrical cardioversion. A femoro-femoral VA ECMO was implanted due to severe biventricular dysfunction and ventricular arrhythmia, associated with continuous renal replacement therapy. Taxol A, taxol B and baccatin III were detected and measured in both blood and urine samples by high-performance liquid chromatography tandem mass spectrometry, and kinetics suggested urinary excretion. Two days after hospital admission, VA ECMO and continuous renal replacement therapy were removed with full recovery of cardiac function. DISCUSSION: Our experience suggests that circulatory assistance by VA ECMO and continuous renal replacement therapy seem to be effective safe second-line therapeutic options in critically ill cases of severe yew intoxication with refractory cardiogenic shock due to arrhythmia.

Toxalbumin exposures: 12 years' experience of U.S. poison centers.

BACKGROUND: Toxalbumins are natural plant toxins purported to be highly toxic. The purpose was to evaluate toxalbumin exposures reported to U.S. poison centers to determine plants involved and their toxicities. METHODS: A retrospective review of National Poison Data System data on acute toxalbumin exposures with known outcomes from 2000 through 2011 was performed. RESULTS: There were 1164 exposures. The majority involved one route (1135; 97.5%), mostly ingestions (904; 79.7%) or dermal (166; 14.3%). Most patients developed no effects (694; 59.6%) or minor effects (374; 32.1%). Moderate or major effects occurred in 8.3% with 66.6% ingestions and 23.9% dermal. There were no deaths. Exposures to the plants Ricinus communis and Robinia pseudoacacia were most common (33.8% and 32.9%, respectively), with gastrointestinal effects from R. communis (vomiting 19.6%, diarrhea 8.9%, nausea 7.9%) and dermal effects from R. pseudoacacia (puncture 28.7%, dermal irritation/pain 27.9%, and edema 13.3%). CONCLUSIONS: While toxalbumin plant exposures were generally well-tolerated, continued evaluation of risk is warranted since plants were primarily identified by the public. Major effects occurred in under 1% of cases overall, and not at all following unintentional ingestions. These findings should help allay concerns that unintentional ingestions of toxalbumin plants by young children will cause serious toxicity and possibly death.

The relative toxicity of Delphinium stachydeum in mice and cattle.

Larkspurs (Delphinium spp.) are poisonous plants on rangelands throughout the Western United States and Canada. Larkspur-induced poisoning in cattle is due to norditerpene alkaloids that are represented by two main structural groups of norditerpene alkaloids, the N-(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and the non-MSAL type. Information on the alkaloid composition and resulting toxicity in mice and cattle is lacking for a number of Delphinium species, including Delphinium stachydeum. The objective of this study was to determine the alkaloid composition of D. stachydeum and to characterize its relative toxicity in mice and cattle compared to two reference species Delphinium barbeyi and Delphinium occidentale. D. stachydeum contains the non-MSAL-type alkaloids but not the MSAL-type alkaloids. D. stachydeum was less toxic than D. barbeyi and D. occidentale in the mouse model. D. stachydeum was less toxic than the MSAL-containing D. barbeyi but much more toxic than the non-MSAL-containing D. occidentale in cattle as measured by heart rate and time of exercise. These results indicate that predictions of Delphinium toxicity can't be accurately made based solely on results from the mouse model or the absence of the MSAL-type alkaloids in the plant.

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.

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.

[Acute intoxication in adults - what you should know]. / Akute Intoxikationen bei Erwachsenen - was Sie wissen sollten.

Ingestion of household products and plants are the leading cause for calls to the poison control centres as far as children are involved. Severe intoxication in children has become infrequent due to childproofed package and blister packs for drugs. Chemical accidents in adults give rise to hospital admission in only 5 %. Suicidal selfpoisonings are still a challenge for paramedics, emergency and hospital doctors. Natural toxins as amatoxins, cholchicine and snakebites can lead to severe intoxication. Sedatives, antidepressants and analgesics are the drugs which are often used for suicidal intent due to their availability. Quetiapine and paracetamol are the drugs which are ingested for attempted suicide/ suicide mostly. The treatment of poisoning centers on the severity which can be judged by the poison severity score, the Reed classification or the GCS.Most intoxicated patients can be treated symptomatically or by intensive care measurements. Antidotal treatment however is needed for some specific poisonings.Exact sample drawing is essential for diagnostic and forensic purposes. There is no evidence based proof for the effectiveness of primary detoxification from the gastrointestinal tract like forced emesis, gastric lavage or the use of cathartics. Early after the ingestion of a harmful substance the administration of activated charcoal seems advisable. Hemodialysis can remove water soluble substances with a small volume of distribution. Multiple charcoal administration may exhibit some influence on secondary detoxification. Provision of evidence of the efficacy for newer antidotes like hydroxocobalamin in smoke inhalation, fomepizol for toxic alcohols and silibinin for amanita poisoning are emerging. Two recently recommended therapeutic principles have still to demonstrate their ability: Firstly the treatment of patients with calcium receptor antagonistic and beta-receptor antagonistic agents poisoning by high dose of insulin plus glucose, secondly the treatment for severe intoxication with cardiotoxic and psychotropic drugs with a lipid emulsion (Lipid rescue).It is essential for all doctors to contact a poison control center whenever they are confronted with an intoxicated patient. There they can get advice about which dose is toxic and about the newest therapeutic procedure.

Alpha-adrenergic receptor blocking effect of Cleistanthus collinus (Roxb.) Benth. and Hook f. leaf extract on guinea pig isolated smooth muscle preparations.

Aqueous extract of C. collinus leaves inhibited norepinephrine induced contraction in guinea pig vas deferens and aortic strip in a dose-dependent manner. Inhibition of acetylcholine induced contraction in ileum was dose independent. C. collinus extract per se had no effect on isolated guinea pig vas deferens and aortic strip, but inhibited norepinephrine induced contraction in a dose-dependent manner probably by its antagonist action on alpha-adrenergic receptor. It had inconsistent effect on guinea pig ileum in vitro preparation.

Causes and prevention of herb-induced aconite poisonings in Asia.

The recent reports from Hong Kong, Taiwan, China and Korea were reviewed to determine the causes and prospects for prevention of herb-induced aconite poisonings. The contributory factors included overdose (use of greater than the recommended doses), faulty processing (after harvest and during decoction), use of tincture (herbal medicinal wine), use of crude aconite roots (for preparing decoction, proprietary medicines and tincture), lack of standardisation in processing of aconite roots and preparation of tincture and proprietary medicines, unsupervised use of aconite roots and contamination or mix-up with aconite roots. As tincture (herbal medicinal wine) made from aconite roots contains a much larger amount of Aconitum alkaloids, the public should be strongly discouraged from making their own and taking it by mouth. Aconite roots should only be used after post-harvest processing and proper decoction. The public should be educated on the hazards from unsupervised use and improper decoction of processed aconite roots. There should be regular publicity measures to promote awareness among the herbalists and to publicise the risk of serious cardiotoxicity if the recommended doses of processed aconite roots are exceeded. The processing of aconite roots and their proprietary preparations should be standardised. Quality control of processed aconite roots and their proprietary preparations should be strengthened. National reporting or monitoring systems can be used to identify the causes of aconite poisonings and assess the impact of preventive measures.

Cardiotoxicity from 'safe' herbomineral formulations.

Many herbomineral preparations are currently being used as therapeutic remedies for common ailments. Commonly known cardiotoxic herbs are Aconitum ferox (aconite), Areca catechu (betel nut), Thevetia peruviana (yellow oleander) and Cleistanus collinus (oduvan). Herbs mixed with lead, copper and/or mercury are known to be highly toxic. They produce cardiac arrhythmias, mainly ventricular ectopics, ventricular tachycardia and various degrees of arterioventricular (AV) blocks. We report 12 such successive cases where the patients developed vague feelings of discomfort, dizziness, chest discomfort and ventricular arrhythmias following herbal drug ingestion which warranted the immediate discontinuation of the drug. Three of the patients died. This paper emphasizes the risk of unsupervised use of herbomineral preparations by patients who believe that the remedies are always 'safe' and the urgent necessity for the pharmacognostic identification of the constituent herbs, their toxicological studies, uniform nomenclature, authenticity and standardization of plants and their parts before advocating them for therapeutic use.