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Background: The Japanese chaff flower, Achyranthes japonica, is used as complementary medicine to control degenerative arthritis. Although commonly used in South Korea, there has been no report of side effects. We report the first case of acute interstitial nephritis (AIN) that occurred in a woman who ingested A. japonica extract for 4 months., Case Presentation: A 56-year-old Korean woman was admitted for deterioration of renal function. She had general weakness and nausea for 1 month. Her initial blood urea nitrogen and serum creatinine levels were 26.3 mg/dL and 3.2 mg/dL, respectively. She acknowledged ingesting A. japonica extract for the past 4 months. Renal histology demonstrated AIN represented by immune cell infiltration into the interstitium, tubulitis, and tubular atrophy, but the glomeruli were intact. A. japonica was discontinued immediately and conservative management was started. Renal function was nearly restored to the baseline level without medication after 13 months., Conclusion: This is a rare case report of AIN associated with a pure A. japonica extract. In the case of unknown etiology of AIN, physicians should ask about the use of herbal medicines, nutraceuticals, and traditional folk medicines including A. japonica.

Ethnopharmacological Relevance: The different plant parts of Cassia occidentalis Linn, (CO) such as root, leaves, seeds and pods have traditionally been used in multifarious medicines for the treatment of dysentery, diarrhea, constipation, fever, eczema, cancer and venereal diseases., Materials and Methods: A systematic search of literature has been done in books and scientific databases like Science Direct, Pubmed, Google Scholar and Scopus etc. These sources were used to compile, analyze and review the information regarding the phytochemistry, toxicology and mechanism of toxicity of CO. The various references on this subject are cited in our review ranging from 1956 to 2019., Results: Unintentional exposure of CO causes serious pathological condition in children, known as hepato-myo-encephalopathy (HME). The toxicity after CO consumption is associated with the presence of anthraquinones (AQs), a class of secondary plant metabolites. These AQs at high concentrations are known to cause detrimental effects on essential vital organs such as liver, kidney, spleen, brain, muscle and reproductive organs. The animal studies in rodent models as well as clinical investigations have clearly revealed that CO toxicity is associated with enhanced hepatotoxicity serum markers (ALT, AST, and LDH) and presence of necrotic lesions in liver. Furthermore, CO also causes vacuolization in muscle tissue and increases the level of CPK which is a prominent muscle damage marker. Apart from these target organs, CO consumption also causes neuronal damage via disturbing the levels of different proteins such as (GFAP and b-tubulin III). The mechanistic studies show that AQs present in CO have the potential to disturb the cellular homeostasis via binding to DNA, increasing the production ROS and showing inhibitory effects on essential enzymes etc. Therefore, AQs have been observed to be the primary culprit agents contributing to the toxicity of CO in children and animals., Conclusion: Despite its therapeutic potential, CO consumption can be detrimental if consumed in high amounts. A thorough analysis of literature reveals that AQs are the primary factors contributing to toxicity of CO seeds. Exposure to CO seeds causes HME, which is a serious life threatening condition for the malnourished children from lower strata. Multiple mechanisms are involved in the CO induced HME in patients. Lack of appropriate diagnostic measures and a poor understanding of the CO toxicity mechanism in humans and animals complicate the clinical management of CO poisoning subjects. Therefore, development of point of care diagnostic kits shall help in early diagnosis & suitable management of CO poisoning., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To report a near-fatal poisoning after intentional injection of ricin from a castor bean ( Ricinus communis ) extract., Case Report: A 21 year-old man self-injected ∼3 mL of a castor bean extract intramuscularly and subcutaneously in the left antecubital fossa. Upon admission to our ED (1 h post-exposure; day 1, D1) he was awake and alert, but complained of mild local pain and showed slight local edema and erythema. He evolved to refractory shock (∼24 h post-exposure) that required the administration of a large volume of fluids and high doses of norepinephrine and vasopressin, mainly from D2 to D4. During this period, he developed clinical and laboratory features compatible with systemic inflammatory response syndrome, multiple organ dysfunction, capillary leak syndrome, rhabdomyolysis, necrotizing fasciitis and possible compartment syndrome. The patient underwent forearm fasciotomy on D4 and there was progressive improvement of the hemodynamic status from D7 onwards. Wound management involved several debridements, broad-spectrum antibiotics and two skin grafts. Major laboratory findings within 12 days post-exposure revealed hypoalbuminemia, proteinuria, thrombocytopenia, leukocytosis and increases in cytokines (IL-6, IL-10 and TNF-α), troponin and creatine kinase. Ricin A-chain (ELISA) was detected in serum up to D3 (peak at 24 h post-exposure), with ∼79% being excreted in the urine within 64 h post-exposure. Ricinine was detected in serum and urine by LC-MS up to D5. A ricin A-chain concentration of 246 µg/mL was found in the seed extract, corresponding to the injection of ∼738 µg of ricin A-chain (∼10.5 µg/kg). The patient was discharged on D71, with limited range of motion and function of the left forearm and hand., Conclusion: Ricin injection resulted in a near-fatal poisoning that evolved with septic shock-like syndrome, multiple organ dysfunction and necrotizing fasciitis, all of which were successfully treated with supportive care.

Background: Interest in the Southeast Asian natural remedy kratom has increased in Western countries recently, along with increasing concern over its potential toxic effects. Objective: To describe and compare demographics, common co-exposure substances, clinical effects, treatments, and medical outcomes of kratom "abuse" exposures in the United States (US) and Thailand. Methods: This is a retrospective analysis of kratom "abuse" exposures, defined as use when attempting to gain a psychotropic effect, reported to the National Poison Data System (NPDS) in the US and the Ramathibodi Poison Center (RPC) in Thailand from 2010 to 2017. Multivariate analysis identified risk factors for severe medical outcomes, defined as both ICU admissions and death. Results: Nine-hundred-twenty-eight cases were included (760 from NPDS and 168 from RPC). A greater proportion of cases involved co-exposures in Thailand (64.8% versus 37.4%; odds ratio [OR] = 3.10, 95% confidence interval [CI] = 2.15-4.47, p < .01). Both countries had a similar prevalence of opioid and benzodiazepine co-ingestions, but the US had more co-ingestions with other sedatives (4.6% versus 0%, OR = 0, 95% CI = 0-0.47, p < .01). Common clinical effects included tachycardia (30.4%), agitation/irritability (26.2%), and drowsiness/lethargy (21.1%). Six deaths occurred, including one single-substance exposure in the US, three multiple-substance exposures in the US, and two multiple-substance exposures in Thailand. Severe medical outcomes were reported more frequently in the US (OR = 18.82, 95% CI = 5.85-60.56, p < .01). Conclusions: Despite lower frequencies of co-ingestants overall, US kratom abuse exposures yielded greater clinical severity. This disparity may be attributable to differences in the products labeled "kratom," greater sedative co-exposures in the US, and/or differences in population genetics or use patterns.

Kratom mainly grows in Southeast Asia. It is widely used for pain management and opioid withdrawal, which is available online for cheaper prices. Alkaloids extracted from kratom such as mitragynine and 7-hydroxy mitragynine exhibit analgesic properties by acting through µ receptors. Commonly reported side effects of kratom include hypertension, tachycardia, agitation, dry mouth, hallucinations, cognitive and behavioral impairment, cardiotoxicity, renal failure, cholestasis, seizures, respiratory depression, coma, and sudden cardiac death from cardiac arrest. Rhabdomyolysis is a less commonly reported lethal effect of kratom. Limited information is available in the literature. In this article, we present a case of a 45-year-old female who is overdosed with kratom and presented with lethargy, confusion, transient hearing loss, and right lower extremity swelling and pain associated with weakness who was found to have elevated creatinine phosphokinase. She was diagnosed with rhabdomyolysis, compartment syndrome, multiorgan dysfunction including acute kidney injury, liver dysfunction, and cardiomyopathy. She underwent emergent fasciotomy and required hemodialysis. Her renal and liver function subsequently improved. We described the case and discussed pharmacology and adverse effects of kratom toxicity with a proposed mechanism and management. We conclude that it is essential for emergency physicians, internists, intensivists, cardiologists, and nephrologists to be aware of these rare manifestations of kratom and consider a multidisciplinary approach.

The historical practice of brewing poppy tea for its opioid-like effects is reoccurring with modern-day substance users. We present four postmortem cases with toxicology results that serve as case studies for the potential hazards of poppy tea ingestion. There is limited information regarding the risks of this practice due to the variability of the morphine content of the opium exuded from the plant. While internet tea recipes offer guidance, differences in poppy cultivation, washing, and infusing time are some of the reasons why the beverage may contain inconsistent and clinically significant alkaloid concentrations for each preparation. Variability in opioid tolerance along with additional drugs taken will impact the overall degree of toxicity experienced from the opiates in the tea. Advancements in the genetic modification of the poppy plant could greatly alter the ratio of alkaloids seen in biological fluids and will be highly dependent on the source of the poppy product. The blood concentrations of free morphine and free codeine in cases 1-3 where the toxicity from the tea was considered the primary cause of death were 0.94 and 0.11 mg/L, 0.62 and 0.034 mg/L, and 0.16 and 0.010 mg/L, respectively. The urine concentrations of morphine and codeine were 13 and 0.94 mg/L in case 1 and 16 and 1.6 mg/L in case 2, respectively. The opium alkaloids thebaine and laudanosine were identified qualitatively by our routine organic base/neutral drug detection procedure., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Moraea pallida Bak. (yellow tulp) poisoning is the most important plant cardiac glycoside toxicosis in South Africa. The toxic principle, a bufadienolide, is 1α, 2α-epoxyscillirosidine. The aim was to investigate the potential to develop a vaccine against epoxyscillirosidine. Epoxyscillirosidine, proscillaridin and bufalin, were successfully conjugated to hen ovalbumin (OVA), bovine serum albumin (BSA) and keyhole limpet haemocyanin (KLH). There was a low immune response following vaccination of adult male New Zealand White rabbits with epoxyscillirosidine-OVA (n = 3) and OVA (n = 3) using Freund's adjuvant in Trial (T) 1. The immune response improved significantly in T2 following doubling of the dose to 0.8 mg/rabbit and changing the adjuvant to Montanide. In T3, the rabbits (n = 15), allocated into 5 equal groups, vaccinated with proscillaridin-BSA, bufalin-BSA, epoxyscillirosidine-KLH, epoxyscillirosidine-BSA and BSA respectively, using Montanide adjuvant, developed antibodies against the administered immunogens, with epoxyscillirosidine-KLH inducing the highest immune response. Proscillaridin and bufalin antibodies cross-reacted with epoxyscillirosidine in an enzyme linked immunosorbent assay. The conjugation methodology will be adjusted in the future to target optimal conjugation efficiency. Additional vaccination will be conducted in search of neutralizing antibodies against the yellow tulp toxin. The cross-reactivity of proscillaridin and bufalin antibodies with epoxyscillirosidine could be studied in future to explore the potential to prevent yellow tulp poisoning., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Illicit substance use is an increasing problem all over the world, especially in adolescents and young adults. It is a challenge to make a definitive diagnosis of a specific substance in a poisoning case without toxicology laboratory confirmation. We confirmed the presence of N,N-dimethyltryptamine (DMT) by liquid chromatograph tandem mass spectrometer (LC/MS/MS) in biologic samples from two patients who presented with signs and symptoms consistent with sympathomimetic toxicity following the consumption of an herbal stew. Case: Two patients consumed an herbal stew together developed DMT poisoning from the interaction between Syrian rue seeds containing alkaloids with monoamine oxidase inhibitor (MAOI) activity and Acacia tree bark containing DMT. Patients' blood and spot urine was analyzed by LC/MS/MS which revealed the presence of DMT (case 1 urine: 1206 ng/mL, serum: 25 ng/mL; case 2 urine: 478 ng/mL, serum: undetectable) and harmaline (case 1 urine: 1564 ng/mL, serum: 3.3 ng/mL; case 2 urine: 1230 ng/mL, serum: undetectable). Discussion: The diagnosis of DMT poisoning is confirmed by the presence of DMT and harmaline in patients' serum and urine. Case 1 exhibited more severe signs and symptoms (e.g., altered consciousness, rhabdomyolysis, and elevated liver enzyme) than case 2. This may be explained by the presence of psychoactive DMT levels in the blood of case 1 whereas DMT was undetected in the blood of case 2. Conclusions: Consumption of an herbal stew composed of Syrian rue seeds and Acacia tree bark may be equivalent to taking a combination of DMT and MAOI, which may precipitate a sympathomimetic syndrome. Physicians should be aware that unusual clinical presentations may be the result of drug-drug interactions from a mixed herbal preparation.

Cleistanthus collinus is a poisonous shrub used for deliberate self-harm in rural areas of South India and intake of boiled decoction of leaves is a common method of self-harm. Distal renal tubular acidosis (dRTA) is an important clinical symptom observed in C. collinus poisoning, and renal V-ATPases may be potential targets of damage. However, a lack of understanding of molecular mediators involved hampers medical management, which is mainly supportive. We hypothesized that C. collinus poisoning induces renal oxidative stress; probably by inducing mitochondrial uncoupling, which compromises V-ATPase activity to ultimately produce dRTA. This was tested by exposing renal BBMV, kidney cells in culture, and Wistar rats to C. collinus poisoning. Exposure to C. collinus aqueous extract resulted in significant elevations in the lipid peroxidation marker, conjugated dienes, in cell culture and in vivo . A significant decrease in mitochondrial respiratory control ratio was observed in kidneys from C. collinus -treated animals suggesting that mitochondrial oxidative phosphorylation is uncoupled. This was accompanied by significant increase in ADP levels and a decrease in proton pump activity. Thus, these results demonstrate that C. collinus poisoning induces oxidative stress which influences proton pump activity, probably due to feedback inhibition by elevated ADP levels because of mitochondrial dysfunction in the rat kidney.

Context: Kratom, or Mitragyna speciosa , is a plant indigenous to Southeast Asia that has gained national attention in the United States for its increased use in the self-management of opioid withdrawal and pain, as well as for concerns about its safety. Methods: This study analyzes exposures to kratom reported to poison control centers (PCCs) in the United States during 2011-2017 from the National Poison Data System (NPDS). Discussion: From 2011 through 2017, 1807 kratom exposures were reported to United States PCCs. Almost two-thirds (65.0%) of these exposures occurred during 2016-2017. Most exposures occurred among adults ≥20 years (88.9%), males (70.8%), at a residence (86.1%), and were intentional (74.3%). Among first-ranked kratom exposures, 31.8% resulted in admission to a health care facility (HCF) and 51.9% in a serious medical outcome. Multiple-substance exposures were associated with greater odds of admission to a HCF (OR: 2.80; 95% CI: 2.21-3.55) and a serious medical outcome (OR: 2.25; 95% CI: 1.77-2.85) compared with single-substance exposures. There were 11 deaths associated with kratom exposure, including two that occurred after exposure to kratom only. Among kratom-only exposures, 86.1% resulted in one or more clinical effects. The most common clinical effects were agitation/irritability (22.9%) and tachycardia (21.4%). There were seven neonatal exposures, including five experiencing withdrawal. Conclusions: Kratom is associated with a variety of serious medical outcomes, especially when used with other substances. More research is needed to define the human response to kratom. Increased regulation of kratom products would help guarantee product quality and safety. Individuals who choose to use kratom should be educated about its potential risks, including the dangers of using it in combination with other substances.

Objective: Aconitum plants (Ranunculaceae) exhibit toxicity, and accidental ingestion of the plants has been reported in Japan. Identifying the cause of poisoning is important for emergency medical treatment, and a rapid and simple detection technique is required for the identification of poisoning cause. In the present study, we developed a rapid and simple method for detecting Aconitum plant DNA using a loop-mediated isothermal amplification (LAMP) assay., Results: Specific LAMP primers for Aconitum plants were designed based on the trnL-trnF intergenic spacer region. Using the LAMP primers, the LAMP assay included an initiation reaction of 10 min followed by amplification for 20 min at the isothermal reaction temperature of 65 °C. The LAMP reaction was demonstrated to be specific and highly sensitive to Aconitum plants, given that the assay can be used for 1 pg of purified DNA. Using raw extracted DNA as template, the entire detection procedure from DNA extraction to final detection required only 30 min. Moreover, the protocol identified samples containing approximately 5 mg of Aconitum plants cooked and digested with artificial gastric juice. The currently proposed protocol exhibits good potential as a screening method of Aconitum plant poisoning for emergency medical care.

Ricin is a highly toxic agent derived from the castor bean plant (Ricinus communis). Poisoning occurs commonly by oral ingestion of the beans. Injection of ricin is believed to be more lethal. Ricin is a large glycosylated protein difficult to detect in clinical samples. Instead, ricinine, a small alkaloid found in the same beans, is used as surrogate marker for ricin exposure. We describe a simple LC-MS/MS method for the detection of ricinine in serum, blood and urine, validated according to EMA guidelines and successfully applied to patient samples of a suicidal death after injection of a castor bean extract. A 26-year-old man self-presented to the emergency department with severe abdominal cramps and nausea after injection of a castor bean extract. Due to rapid deterioration of his hemodynamic function despite early aggressive fluid resuscitation, he was transferred to ICU. Abdominal cramps worsened and a fulminant diarrhea developed, resulting in hypovolemic shock and cardiorespiratory collapse. Despite full supportive therapy, the patient died approximately 10 hours after injection due to multiple organ failure. Ricinine was quantified by LC-MS/MS after LLE with diethyl ether using ricinine-D3 as internal standard. Six hours after injection, ricinine concentrations in serum and blood were 16.5 and 12.9 ng/mL, respectively, which decreased to 12.4 and 10.6 ng/mL, 4 hours later. The urinary concentration was 81.1 ng/mL 7 hours after injection, which amply exceeded the levels previously reported in similar cases with lethal outcome. Concentrations of ricinine, compatible with a lethal exposure to castor beans, were detected in serum, blood and urine. Ricinine was also found in bile and liver tissue., (©The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A 2-year-old girl required medical attention for a sudden onset of repetitive tonic-clonic convulsions after ingesting 20-30 ginkgo seeds. Concentrations of the major forms of circulating vitamin B 6 , pyridoxal-5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid, as well as the known ginkgo seed toxin 4'-O-methylpyridoxine (MPN) were measured in the serum and cerebrospinal fluid (CSF). PLP is an active form of vitamin B 6 and necessary for γ-aminobutyric acid (GABA) production. High MPN concentrations were observed in both the serum and CSF. As the PLP to PL ratio was markedly decreased in serum and CSF examinations, we suspected the ratio to be important in GABA production. This case report provides novel information on the metabolism of vitamin B 6 in humans as a result of ginkgo seed poisoning., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Introduction: Suicide is a major public health challenge in Kerala. Majority of adult poisoning is intentional. Most of those who attempt 'deliberate self harm' are young adults and many a time the reason is trivial., Objectives: To find out the pattern of poisoning, prognostic factors in different type of poisoning, precipitating factors for deliberate self harm and to suggest preventive measures., Methodology: This was a prospective observational study conducted among patients admitted with history of poisoning in a tertiary care centre in Kerala. Detailed history, physical examination, relevant lab investigations were done in all the patients. Psychiatric assessment and counselling was done in all survivors., Results: A total of 195 patients were included in this study-109 males and 86 females. The intention of poisoning was suicidal in 98.82% of cases. The mortality rate was 13.33%. Common poisons consumed were odollam, drugs, pesticides and rodenticides. Majority of deaths were due to organophosphorous compounds (42.31%) followed by odollam (38.46%). The common precipitating factors were family problems, personal stressors and marital discord in both sexes. Psychiatric assessment showed adjustment disorder as the commonest problem followed by impulsive act., Conclusion: The common poisons ingested are organophosphorous compounds, drugs and odollam. Organophosphorous and odollam carries higher mortality. Pesticide regulation, use of less toxic pesticides in agriculture, early management and quick referral to well equipped hospitals will help in reducing mortality. Suicide prevention programmes like psychosocial support and counselling, raising public awareness about deliberate self harm and alcohol de-addiction programmes will help in reducing the incidence of deliberate self harm., (© Journal of the Association of Physicians of India 2011.)

We report a case of 50-year-old male patient from tribal area in South Indian state of Telangana, who ingested the liquid extract from crushed leaves of the plant, cleistanthus collinius with the intention of self-harm. Immediate gastric lavage and activated charcoal administration was done and the patient was subsequently admitted into an acute medical care unit. During first 24 hours of monitoring, the patient was clinically stable. There was mild normal anion gap metabolic acidosis and hypokalaemia on arterial blood gas (ABG) and was corrected accordingly. On second day of admission he developed acute onset shortness of breath. Chest auscultation revealed extensive bilateral coarse crackles. Chest X-ray was suggestive of acute respiratory distress syndrome (ARDS). The patient had to be intubated. Continuous renal replacement therapy (CRRT) was initiated in view of worsening metabolic acidosis and unstable haemodynamics. In spite of appropriate intensive care measures, the patient succumbed to illness. Immediate gastric lavage and activated charcoal administration was done and the patient was subsequently admitted into an acute medical care unit. During first 24 hours of monitoring, the patient was clinically stable. There was mild normal anion gap metabolic acidosis and hypokalaemia on ABG and was corrected accordingly. On second day of admission, he developed acute onset shortness of breath. Chest auscultation revealed extensive bilateral coarse crackles. Chest X-ray was suggestive of ARDS. The patient had to be intubated on day 2. CRRT was initiated in view of worsening metabolic acidosis and unstable haemodynamics. In spite of appropriate intensive care measures, the patient gradually deteriorated, had cardiac arrest and passed away on day 5 of his hospital stay., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Throughout Morocco, cade oil is used in folk medicine for many purposes, in particular for atopic dermatosis. It is also used as a wormer. Cade oil poisoning of newborns and infants thus often has an iatrogenic origin, resulting especially from the ingestion of a significant amount or from a prolonged and extensive cutaneous application. Thus, this oil, used for therapeutic purposes, is responsible for a non-negligible number of cases of poisoning, some fatal. We report a case of poisoning after cutaneous application of cade oil in a 2-month-old infant. The outcome was fatal. This report calls attention to the real possibility of this event and emphasizes the interest of preventing it by promoting information to families in Morocco.

The leaves of Mitragyna speciosa (commonly known as kratom), a tree endogenous to parts of Southeast Asia, have been used traditionally for their stimulant, mood-elevating, and analgesic effects and have recently attracted significant attention due to increased use in Western cultures as an alternative medicine. The plant's active alkaloid constituents, mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as partial agonists at mu-opioid receptors and competitive antagonists at kappa- and delta-opioid receptors. Furthermore, both alkaloids are G protein-biased agonists of the mu-opioid receptor and therefore, may induce less respiratory depression than classical opioid agonists. The Mitragyna alkaloids also appear to exert diverse activities at other brain receptors (including adrenergic, serotonergic, and dopaminergic receptors), which may explain the complex pharmacological profile of raw kratom extracts, although characterization of effects at these other targets remains extremely limited. Through allometric scaling, doses of pure mitragynine and 7-hydroxymitragynine used in animal studies can be related to single doses of raw kratom plant commonly consumed by humans, permitting preliminary interpretation of expected behavioral and physiological effects in man based on this preclinical data and comparison to both anecdotal human experience and multiple epidemiological surveys. Kratom exposure alone has not been causally associated with human fatalities to date. However, further research is needed to clarify the complex mechanism of action of the Mitragyna alkaloids and unlock their full therapeutic potential. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.', (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Yew plants are evergreen shrubs which are widely spread throughout the northern hemisphere. Taxane alkaloid derivatives, mainly taxine B, represent the main toxins of Taxus baccata and are highly cardiotoxic. Due to the lack of randomized clinical trials, case reports on accidental or suicidal yew intoxications build the only source of knowledge of clinical treatment options., Case Report: We report the case of a suicidal yew ingestion admitted to our hospital under prolonged cardiopulmonary resuscitation due to pulseless electrical activity. Extra-corporeal life support (ECLS) was established to maintain adequate organ perfusion. Repeated administration of digoxin-specific Fab antibody fragments, which cross-react with taxine, was associated with an immediate conversion from asystole to broad-complex bradycardia and a gradual normalization of the electrocardiogram (ECG). This was paralleled by a recovery of the cardiac function and weaning from the ECLS. The taxine metabolite 3,5-dimethoxyphenol could be detected by mass spectrometry before but not after the first Fab-fragment treatment. In contrast, the total amount of taxine (including the neutralized, Fab fragment-bound fraction) was increased after each Fab fragment administration, suggesting an accumulation of neutralized, since antibody-bound taxine in the blood by anti-digoxin Fab fragments., Discussion: In conclusion, the successful clinical course of this case suggests a benefit of an early anti-digoxin Fab-fragment administration for the treatment of yew intoxication., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The yew (Taxus baccata) is a common evergreen tree containing the toxin taxine B. Between 42 and 91 g of yew leaf is lethal to a 70-kg adult. The objective of this article is to present an overview of findings in fatal yew intoxications., Methods: A search using MeSH terms was performed in PubMed for yew intoxications in the period between January 1960 and August of 2016., Results: We describe a total of 22 cases. Fatal intoxications can be divided into intoxications by leaves, by pulp, by bark and by yew tea. Recognizing yew tea intoxication is difficult since tea no longer contains any botanically recognisable parts. In autopsy and external examination no characteristic findings are reported, regarding the presence of parts of plants., Conclusions: Indications for yew tree intoxications at a post-mortem examination and autopsy are limited to finding parts of yew tree. The absence of recognisable parts can result in yew intoxications being overlooked. Therefore toxicological screening is recommended in unexplained deaths., (Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: The purpose of this study was to investigate grayanotoxin (GTX) levels in the blood of patients with GTX intoxication and in the consumed Rhododendron liqueur, and to determine whether there was an association between blood GTX level and the patient's clinical status., Methods: In September 2015, six patients were concurrently presented to the emergency department with various toxicity symptoms, which occurred after the consumption of Rhododendron liqueur at the same toxin concentration. Liquid chromatography-tandem mass spectrometry analysis was conducted on blood samples obtained from six cases of GTX intoxication treated in our emergency department., Results: At the initial evaluation in the emergency department, the mean arterial pressure of the patients ranged from 36.7 to 76.7 mm Hg. The concentrations of GTX-I and GTX-III in Rhododendron liqueur were 1.436 and 16.907 ng/mL, respectively. The initial blood GTX-III and GTX-I levels ranged from 2.9 to 58.0 ng/mL and the lower limit of quantification (LLOQ) to 8.33 ng/mL, respectively. After 20 h, the mean arterial pressure ranged from 76.7 to 93.3 mm Hg, while the blood GTX-III and GTX-I levels ranged from the LLOQ to 17.8 and 2.52 ng/mL, respectively., Discussion: We estimated that the minimum blood GTX-III and GTX-I levels that caused hypotension were between 17.83 and 27.3 ng/mL, and 2.52 and 4.55 ng/mL, respectively.

The use of traditional products for therapeutic purposes in the newborn cause many cases of severe poisoning, especially in newborns. The aim of this study was to identify the main medicinal plants causing poisoning and emphasize the seriousness of poisonous plants. We report a series of eight newborns admitted for intake of poisonous medicinal plants admitted to the neonatal unit and neonatal intensive care unit at the Fez (Morocco) Hassan II University Hospital in 2014. The reasons for use were dominated by the infant's refusing to suckle. Clinical signs at admission were neurological signs and respiratory distress. The decision was spontaneously declared by the family for only two patients. A particular smell of the urine and unusual lesion associations were the main signs drawing the attention of physicians in other cases. The amounts and rates differed. Laboratory tests revealed renal failure in two cases. Transaminases (SGOT and SGPT) were greater than three times normal and the TP was below 50% in two newborns. Hemoglobin less than 9g/dL in three cases and thrombocytopenia less than 50,000/mm 3 in two newborns. The main poisonous plants were identified as cade oil and henna. Medicinal plants were associated in all cases. Toxicological analysis was negative in three cases and was not done in the other five cases. The management was symptomatic and etiological. The outcome was favorable in six newborns. Death occurred in two neonates despite resuscitation. Medicinal plants must, like drugs, obey strict rules that only the standard herbal medicine specialist can answer. This necessarily involves the regulation of the profession in our country., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Ayahuasca is a hallucinogenic plant preparation which usually contains the vine Banisteriopsis caapi and the shrub Psychotria viridis. This tea originates from the Amazon Basin where it is used in religious ceremonies. Because interest in these religious groups spreading as well as awareness of use of ayahuasca for therapeutic and recreational purposes, its use is increasing. Banisteriopsis caapi is rich in β-carbolines, especially harmine, tetrahydroharmine and harmaline, which have monoamine oxidase inhibiting (MAOI) activity. Psychotria viridis contains the 5HT2A/2C/1A receptor agonist hallucinogen N,N-dimethyltryptamine (DMT). Usual desired effects include hallucination, dissociation, mood alteration and perception change. Undesired findings previously reported are nausea, vomiting, hypertension, and tachycardia., Methods: All human exposure calls reported to the American Association of Poison Controls Centers' (AAPCC) National Poison Data System (NPDS) between September 1, 2005 and September 1, 2015 were reviewed. Cases were filtered for specific plant derived ayahuasca-related product codes. Abstracted data included the following: case age and gender, exposure reason, exposure route, clinical manifestations, treatments given, medical outcomes and fatality., Results: Five hundred and thirty-eight exposures to ayahuasca botanical products were reported. The majority of the calls to poison control centers came from healthcare facilities (83%). The most common route of exposure was ingestion. Most cases were men (437, 81%, 95% CI 77.7% - 84.3%). The median age was 21 (IQR 18-29). Most exposures were acute. Three hundred thirty-seven (63%) were reported to have a major or moderate clinical effect. The most common clinical manifestations reported were hallucinations (35%), tachycardia (34%), agitation (34%), hypertension (16%), mydriasis (13%) and vomiting (6%). Benzodiazepines were commonly given (30%). There were 28 cases in the series who required endotracheal intubation (5%). Four cases were reported to have had a cardiac arrest and 7 a respiratory arrest. Twelve cases had a seizure. Reports of exposures called to poison centers appeared to increase during this period based on annual estimates. Three fatalities were reported., Conclusions: Ayahuasca use appears to be rising in the United States based on calls to poison control centers. While most use is reported to be safe and well tolerated, with possible beneficial effects, serious and life threatening adverse manifestations are possible. Most of the exposures reported to poison control centers were young people, more likely to be men and already in a healthcare facility. Further research, which includes comprehensive drug testing, will be needed to better identify the risks and effects of ayahuasca use.

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.

Background: Aconitum species are poisonous plants that have been used in Western medicine for centuries. In the nineteenth century, these plants were part of official and folk medicine in the Slovenian territory. According to current ethnobotanical studies, folk use of Aconitum species is rarely reported in Europe. The purpose of this study was to research the folk medicinal use of Aconitum species in Solčavsko, Slovenia; to collect recipes for the preparation of Aconitum spp., indications for use, and dosing; and to investigate whether the folk use of aconite was connected to poisoning incidents., Methods: In Solčavsko, a remote alpine area in northern Slovenia, we performed semi-structured interviews with 19 informants in Solčavsko, 3 informants in Luče, and two retired physicians who worked in that area. Three samples of homemade ethanolic extracts were obtained from informants, and the concentration of aconitine was measured. In addition, four extracts were prepared according to reported recipes., Results: All 22 informants knew of Aconitum spp. and their therapeutic use, and 5 of them provided a detailed description of the preparation and use of "voukuc", an ethanolic extract made from aconite roots. Seven informants were unable to describe the preparation in detail, since they knew of the extract only from the narration of others or they remembered it from childhood. Most likely, the roots of Aconitum tauricum and Aconitum napellus were used for the preparation of the extract, and the solvent was homemade spirits. Four informants kept the extract at home; two extracts were prepared recently (1998 and 2015). Three extracts were analyzed, and 2 contained aconitine. Informants reported many indications for the use of the extract; it was used internally and, in some cases, externally as well. The extract was also used in animals. The extract was measured in drops, but the number of drops differed among the informants. The informants reported nine poisonings with Aconitum spp., but none of them occurred as a result of medicinal use of the extract., Conclusions: In this study, we determined that folk knowledge of the medicinal use of Aconitum spp. is still present in Solčavsko, but Aconitum preparations are used only infrequently.

Cleistanthus collinus, also known as Oduvanthalai in Tamil, is the most commonly encountered plant poison in southern India. The leaves are used for poisoning humans (suicide or homicide) and animals (cattle and fish) and as an abortifacient, especially in rural south India. Although this poisoning is commonly reported in adults, data regarding the use of N-acetylcysteine in pediatric poisoning is lacking. We report two previously healthy male siblings of pediatric age group who ingested the liquid extracted from crushed leaves of this plant given to them by their mother as a means of deliberate harm. Both patients developed distal renal tubular acidosis, with hypokalemia. The younger sibling also developed myocardial toxicity. Other significant findings noted include hypocalcemia, hypomagnesemia and elevated liver enzymes. Both patients received supportive care along with N-acetylcysteine infusion, and showed complete recovery within 10 days., (© The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Wild garlic and related plants are increasingly sought after by fans of natural products. They can be confused with other plants containing colchicine and cause potentially fatal intoxications., Case Report: We report a case of accidental poisoning by Colchicum autumnale, which was mistaken for wild garlic (Allium ursinum). The patient initially presented with mild gastrointestinal symptoms, but progressed rapidly to agranulocytosis, paraparesis, and delirium before the causative agent was identified. The laboratory tests revealed rhabdomyolysis, coagulopathy, alteration of liver tests, and prerenal azotemia. Botanical examination confirmed the incriminated plant (Colchicum autumnale). Serum and urine analysis confirmed the presence of colchicine. The patient required intensive support therapy, and she fully recovered within 8 weeks. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Colchicine poisoning should be considered in the differential diagnosis of patients presenting with gastroenteritis after ingestion of wild garlic., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Kavalactones are a group of compounds found in kava, a beverage or extract prepared from the rhizome of the kava plant (Piper methysticum). Traditionally kava extracts have been used for their anxiolytic and sedative properties. Sales of kava extracts were severely restricted or prohibited in European countries in 2002 following several cases of serious hepatotoxicity. Here we report a case where high concentrations of kavalactones and ethanol were detected in post mortem femoral blood. An injection needle with a 10-mL syringe containing 7.5 mL of slightly yellowish liquid was found next to the victim, and there were numerous needle prints on both lower arms following the venous tracks. No evidence of other cause of death was found in the medico-legal investigation. The case was therefore classified as suicide using an injection of kavalactones intravenously together with alcohol poisoning., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The aim of this is to review deaths associated with the use of Riot Control Agents (RCAs) and to assess how the presenting pathologies is such cases may better inform cause of death conclusions upon autopsy. We also sought to present which additional steps should be added to the Minnesota protocol and the European harmonization of medico-legal autopsy rules in suspected cases of deaths associated with the use of RCAs. We included 10 lethal cases in our study. In three cases, RCAs were found to be the sole cause of death, in three cases RCAs were ruled a secondary cause of death due asphyxia or asthma subsequent to exposure to RCAs and in four cases RCAs were contributory factors to death. In three cases the responsible agents were identified as Chloroacetophenone (CN), Chlorobenzylidene malononitrile (CS) and Oleoresin capsicum (OC) and in the remaining 7 cases, the agent was OC alone. As there are no specific findings in suspected cases of death associated with RCA use, establishing cause of death and whether RCAs are the sole cause or only a contributory factor will be based on the elimination of other possible causes of death. For this reason, a specifically structured autopsy is essential. This specifically structured autopsy should contain basic principles of the Minnesota Protocol and the European harmonization of medico-legal autopsy rules with the following additional steps taken: examination of clothing, eyes, and skin; examination of pharyngeal, tracheobronchial, and eusophegeal mucosas; and a thorough recording of the steps taken by the party conducting the arrest, including other possible causes of in-custody death, as well as a detailed medical history of the deceased., (Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Two horses were referred for methemoglobinemia and hemolytic anemia following 5 acute deaths in their herd from an unidentified toxin source. Horses have a greater risk than other mammalian species of developing methemoglobinemia and hemolytic anemia following ingestion of oxidizing toxins, due to deficiencies in the mechanisms that protect against oxidative damage in erythrocytes. Their susceptibility to oxidative erythrocyte damage is evident in the numerous cases of red maple (Acer rubrum) toxicosis. The suspected toxins causing A. rubrum toxicosis are tannic acid, gallic acid, and a metabolite of gallic acid, pyrogallol. These compounds can be found in a variety of plants, posing a risk to equine health. In order to quickly identify toxin sources, 2 rapid in vitro assays were developed to screen plant extracts for the ability to induce methemoglobin formation or cause hemolysis in healthy equine donor erythrocytes. The plant extract screening focused on 3 species of the genus Pistacia: P. atlantica, P. terebinthus, and P. chinensis, which were located in the horse pasture. Extracts of the seeds and leaves of each species induced methemoglobin formation and resulted in hemolysis, with seed extracts having greater potency. The in vitro assays used in the current study provide a useful diagnostic method for the rapid identification of oxidizing agents from unidentified sources. There is no effective treatment for oxidative erythrocyte damage in horses, making rapid identification and removal of the source essential for the prevention of poisoning., (© 2014 The Author(s).)

Background: Acute poisoning incidents are one of the leading causes of morbidity and hospitalization in several countries. The purpose of this analysis was to compare the patterns of acute poisoning in three countries namely, Botswana, South Africa and Uganda; and examine the similarities and disparities in the patterns of occurrence of acute poisoning based on the sociodemographic factors of the victims, the toxic agents involved, the circumstances surrounding the incidents and their outcomes., Materials and Methods: This paper is based on the re-analysis of data that were collected from January to June 2005 by some Master of Public Health students using a similar data collection tool. A single dataset made of the original individual datasheets was constituted and analysed., Results: Overall, it was found that the mean age of victims of acute poisoning was 20.9 ± 14.5 years; the youngest victim was a 3 months old boy from South Africa; and the oldest was a 75 years old man from Uganda. In descending order, the most common toxic agents involved in poisoning incidents were household products (46.1%), agrochemicals (18.8%), pharmaceuticals (14.0%), animal and insect bites (13.0%), food poisoning (4.5%), as well as plants and traditional medicines (3.6%). Across the three countries, acute poisoning occurred mainly by accident, but the contextual factors of each country led to a pattern of acute poisoning that showed some similarities with regard to the distribution of deliberate self-poisoning among females, teenagers, and young adult victims. There were disparities related to the differential access to toxic agents, based on the age and gender of the victims. Of the 17 deaths reported, 2 (11.7%) were due to traditional medicines; household products were implicated in fatal outcomes in all three countries, though the extent of their involvement varied from country to country., Conclusion: Although plant and traditional medicines caused fewer cases of acute poisoning incidents, they contributed considerably to fatal outcomes.

Unlabelled: Guarana (Paullinia cupana) is the climbing vine native to Amazon Basin, characterized by high caffeine content in its seeds. Guarana extract is a common ingredient of energy drinks used in order to boost energy and physical endurance and increase alertness. Severe caffeine intoxication is rare, but may be life-threatening mostly due to supraventricular and ventricular dysrhythmias., Objectives: We present the case of intentional caffeine poisoning after ingestion of tablets containing guarana extract, complicated by atrial fibrillation., Case Report: A44-year-old man with no significant medical history was admitted to hospital about 21 h after ingestion of guarana extract containing 1.6 g of caffeine. Typical symptoms of caffeine toxicity, i.e. nausea, vomiting, anxiety and palpitaions, occurred shortly after ingestion. On admission, he was conscious, with blood pressure of 136/86 mmHg, heart rate of 106-113 beats per minute, fever of 37.8 °C, and symmetrically increased deep tendon reflexes. QTc interval in electrocardiogram was prolonged to 0.542 s. Laboratory tests revealed hypokalemia, hyperglycemia, leukocytosis, as well as elevated creatinine and creatine phosphokinase levels. Approximately 45 h post ingestion, the patient developed atrial fibrillation with fast ventricular rhythm. Tachydysrythmia subsided after infusion of amiodarone and restoration of electrolyte balance. Echocardiogram revealed presence of asymmetrical hypertrophy of the left ventricle with the systolic anterior motion of the mitral valve and normal left ventricular outflow tract gradient suggesting non-obstructive hypertrophic cardiomyopathy., Conclusion: Acute caffeine poisoning may result in atrial fibrillation, especially in predisposed patients with underlying hypertrophic cardiomyopathy.

A liquid chromatography-tandem mass spectrometry method for simultaneous detection of 22 toxic plant alkaloids, including aconitum alkaloids and their hydrolyzed products (aconitine, hypaconitine, mesaconitine, yunaconitine, crassicauline A, benzoylaconine, benzoylmesaconine, benzoylhypaconine, deacetylyunaconitine, deacetylcrassicauline A), solanaceous tropane alkaloids (atropine, anisodamine, scopolamine, anisodine), sophora alkaloids (matrine, sophoridine, oxymatrine, cytisine, N-methylcytisine), strychnos alkaloids (brucine, strychnine) and colchicine, in herbal and urine samples was developed and validated. Following sample preparation by liquid-liquid extraction, chromatographic separation was achieved on Eclipse XDB C8 column. Identification was based on two multiple reaction monitoring transitions and the relative ion intensity. Method selectivity was demonstrated. The limits of detection were 5ng/mL for all analytes, except 50ng/mL for cytisine. The herbal matrix effects ranged from 89% to 118%, whereas the urine matrix effects were between 91% and 109% for all analytes except cytisine (57%) and N-methylcytisine (67%). The urine extraction recovery ranged from 74% to 110% for all analytes, except cytisine (15%) and oxymatrine (30%). With the good extraction efficiency of the other major sophora alkaloids, the relatively low extraction recovery of the minor sophora alkaloids cytisine and oxymatrine did not affect identification of sophora alkaloids as a group. Carry-over was minimal at less than 0.1%. The method was successfully applied in analysis of 170 cases of suspected herbal poisoning, with aconitum alkaloids, sophora alkaloids, solanaceous tropane alkaloids, and strychnos alkaloids being detected in 53, 42, 18, and 6 cases, respectively., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To observe the pathological changes of major organs in rats with acute Dysosma versipellis poisoning and investigate the toxic mechanism and the injuries of target tissues and organs., Methods: Forty Sprague-Dawley (SD) rats were randomly divided into three experimental groups, which were given the gavage with 0.5, 1.0 and 2.0 LDo doses of Dysosma versipellis decoction, and one control group, which was given the gavage with 1.0 LD0 dose of normal saline. The rats were sacrificed 14 days after Dysosma versipellis poisoning and samples including brain, heart, liver, lung, and kidney were taken. After pathological process, the pathological changes of the major organs and tissues were observed by light microscope and electron microscope. The experimental data were statistical analyzed by chi2 test., Results: The observations of light microscopy: loose cytoplasm of neurons with loss of most Nissl bodies; swelling of myocardial cells with disappearance of intercalated disk and striations; hepatocellular edema with ballooning degeneration; and swelling epithelial cells of renal proximal convoluted tubule with red light coloring protein-like substances in the tube. The observations of electron microscopy: the structures of cell membrane and nuclear membrane of neurons were destroyed; cytoplasm of neurons, obvious edema; and most organelles, destroyed and disappeared. The mortalities of rats after acute poisoning of the four groups increased with doses (P < 0.05)., Conclusion: Acute Dysosma versipellis poisoning can cause multi-organ pathological changes. There is a positive correlation between the toxic effect and the dosage. The target tissues and organs are brain (neurons), heart, liver and kidney.

The powder of henna plant (Lawsonia inermis Linn.) is extensively used as a decorative skin paint for nail coloring and as a hair dye. Most reports of henna toxicity have been attributed to adding a synthetic dye para-phenylenediamine (PPD). PPD is marketed as black henna added to natural henna to accentuate the dark color and shorten the application time. PPD toxicity is well known and extensively reported in medical literature. We report a case of a young Saudi male who presented with characteristic features of acute renal failure and intravascular hemolysis following ingestion of henna mixture. Management of PPD poisoning is only supportive and helpful only if instituted early. Diagnosis requires a high degree of clinical suspicion, as the clinical features are quite distinctive.

Euphorbia paralias is known in traditional medicine as an anti-inflammatory agent, a purgative and for its local anesthetic property. To the best our knowledge, renal toxicity of this substance has not been previously reported. In this paper, we report the case of a 29-year-old male who developed renal damage following ingestion of Euphorbia paralias. He had been on follow-up for nephrotic syndrome since 1986, although irregularly, with several relapses but each responding well to steroid therapy. A kidney biopsy had not been performed earlier due to refusal by the patient. He was off steroids since April 2008 because the patient developed osteoporosis. He was admitted with general malaise and oliguria to our department in May 2009, following repeated vomiting and watery diarrhea for three days. On examination, he was edematous but had normal vital signs except for a pulse rate of 120/min. Hemoglobin was only 5.5 g/dL but with normal white cell and platelet counts. Blood biochemistry showed evidence of advanced renal failure with a serum creatinine level of 1835 μmol/L and urea at 44.6 mmol/L, sodium of 132 μmol/L and potassium at 4.3 mmol/L. He had features of nephrotic syndrome with severe hypoproteinamia and 24-h urinary protein of 10.45 g. Ultrasonography revealed enlarged kidneys with a reduced echogenecity of the medulla and the papillae. Subsequently, after hemodialysis with blood transfusion, a kidney biopsy was performed that showed focal segmental glomerulosclerosis associated with an acute tubular injury. On intensive interrogation, the patient gave a history of ingesting boiled Euphorbia paralias as a native treatment for edema, ten days prior to the onset of the current illness. A diagnosis of acute renal failure (ARF) resulting from the possible nephrotoxic effect of Euphorbia paralias poisoning was made. He was treated with intermittent hemodialysis and corticosteroids. Serum creatinine values improved after 48 days. At six months following the intoxication, serum creatinine of the patient was 240 μmol/L. In cases of unexplained ARF, a toxic mechanism should always be considered and acute renal failure caused by Euphorbia paralias should be included as a cause if renal toxicity is suspected in those places where it is being used as a native medicine.