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.

Homeopatia na oncologia pediátrica: é possível? Uma série de casos / Homeopathy in oncology pediatric: is it possible? case series

A Homeopatia é uma das ciências médicas complementares mais utilizadas para pacientes com Câncer, sendo também utilizada durante o tratamento de crianças com a referida moléstia, havendo relato e debate de seu uso na literatura médica. Visando construir o conhecimento e dividir experiências, relatamos seis casos de crianças e adolescentes com câncer, para os quais realizamos tratamento homeopático, em nossa experiência na cidade de São Paulo. Além da diversidade de sexos e idade, os casos apresentam diagnósticos oncológicos diferentes, bem como momentos diferentes no tratamento, sendo curativo ou paliativo, e os medicamentos homeopáticos, baseados tanto na totalidade sintomática característica quanto no modo reacional para cada indivíduo, puderam ser utilizados para todos com satisfação de famílias e pacientes, mesmo quando o desfecho letal foi a via final no estado paliativo. Assim, a Homeopatia pode também ser prescrita para os casos oncológicos infantis como terapia complementar ao tratamento convencional, sendo a pesquisa neste campo vasta e possível.

Homeopathy is one of the most used complementary medical sciences for cancer patients, and is also used duringtreatment of children with the aforementioned disease, with reports and debate of its use in medical literature. Aiming to build knowledge and sharing experiences, we report six cases of children and adolescents with cancer, for which we carry out homeopathic treatment, in our experience in the city of São Paulo. In addition to the diversity of sexes and age, the cases present different oncological diagnoses, as well as as different moments in the treatment, being curative or palliative, and homeopathic medicines, based both on symptomatic totality characteristic and in the reactional mode for each individual, could be used for everyone with the satisfaction of families and patients, even when the lethal outcome was the final route in the palliative state. Therefore, Homeopathy can also be prescribed for oncological cases children as complementary therapy to conventional treatment, research in this field is vast and possible.

Poison hemlock determination in postmortem samples.

Poison hemlock (Conium maculatum L.) is a weed that grows rampant in many areas of North America. Forensic toxicology laboratories rarely receive requests to analyze biological specimens for the presence of poison hemlock. This report discusses two postmortem cases that were encountered over a decade apart and describes different analytical approaches that may be used to quantify coniine, a primary poison hemlock alkaloid, in biological specimens. The first case is from 2004 and involves a 27-year-old female that was found deceased in a relatively isolated area of California. Based on the presence of plant material at the scene and signs of its ingestion at autopsy, the possibility of hemlock poisoning was considered. Toxicological testing of the blood and gastric content by quantitative selected-ion monitoring Gas Chromatography/Mass Spectrometry (SIM-GC/MS) revealed the presence of coniine at concentrations of 410 ng/mL and 9300 ng/mL, respectively. The second case is from Pennsylvania and was sent for analysis in the spring of 2019. In this case, a male in his forties was found deceased in the kitchen area of a camper. Green substances, in liquid and residue forms, were observed in the sink. Mixtures of leaf-like material were also found in several bowls and pans. Subclavian blood screened positive for coniine by full-scan Gas Chromatography/Mass Spectrometry (GC/MS). Semi-quantitative confirmation testing was performed by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and showed the presence of coniine at a concentration of 35 ng/mL. These analytical approaches can be used to substantiate or exclude poison hemlock exposure as a cause of death.

De novo transcriptome assembly of Conium maculatum L. to identify candidate genes for coniine biosynthesis.

Poison hemlock (Conium maculatum L.) is a notorious weed containing the potent alkaloid coniine. Only some of the enzymes in the coniine biosynthesis have so far been characterized. Here, we utilize the next-generation RNA sequencing approach to report the first-ever transcriptome sequencing of five organs of poison hemlock: developing fruit, flower, root, leaf, and stem. Using a de novo assembly approach, we derived a transcriptome assembly containing 123,240 transcripts. The assembly is deemed high quality, representing over 88% of the near-universal ortholog genes of the Eudicots clade. Nearly 80% of the transcripts were functionally annotated using a combination of three approaches. The current study focuses on describing the coniine pathway by identifying in silico transcript candidates for polyketide reductase, L-alanine:5-keto-octanal aminotransferase, γ-coniceine reductase, and S-adenosyl-L-methionine:coniine methyltransferase. In vitro testing will be needed to confirm the assigned functions of the selected candidates.

What Socrates drank? Comparative chemical investigation of two Greek Conium taxa exhibiting diverse chemical profiles.

Conium divaricatum, even though exhibiting morphological differences in comparison to its congener of European origin Conium maculatum, is still considered a disputed taxon often referred to as a synonym of the latter. Herein, essential oils of various plant tissues from several populations of both taxa were comparatively investigated, showing distinct chemical profiles. In the case of C. divaricatum, the essential oils were dominated by hydrocarbon esters, among which the main constituents 4'-oxodecyl hexanoate, 4'-oxododecyl hexanoate and 4'-oxooctyl hexanoate were isolated and identified as undescribed natural products. In contrast, the essential oils of C. maculatum were dominated by hydrocarbon alkanes, alkenes and ketones, as well as the polyacetylene (Z)-falcarinol. Even though determination of the total alkaloids content and toxicity assessment against the crustacean Artemia salina did not reveal significant differences, the distinct chemical profiles and the morphological differences observed for both taxa, strongly support their distinction as separate species.

Study of Immunotropic Properties of Water-Soluble Polysaccharides Isolated from Conium maculatum Grass.

Addition of water-soluble polysaccharides isolated from Conium maculatum L. to the mouse peritoneal macrophage culture induces classical activation of antigen-presenting cells due to an increase in NO synthase activity and a decrease in arginase expression.

[Unmittelbare Remission eines mit großzelligem B-Non-Hodgkin-Lymphom befallenen inguinalen Lymphknotens unter alleiniger homöopathischer Behandlung mit Conium: Wann ist eine alleinige adjuvant-homöopathische Tumortherapie zulässig und sinnvoll?] / Immediate Remission of an Inguinal Lymph Node Afflicted with Large-Cell B-Non-Hodgkin's Lymphoma Under Sole Homeopathic Treatment with Conium: When Is a Sole Adjuvant-Homeopathic Tumor Therapy Permissible and Useful?

Bei einer 63-jährigen Patientin wird mittels Biopsie eines linksinguinalen Lymphknotens ein großzelliges B-Non-Hodgkin-Lymphom diagnostiziert. Unmittelbar nach Beginn einer homöopathischen Therapie mit Conium C 30 beginnt sich der Lymphknoten in der linken Leiste zurückzubilden. Bei Exzision des Lymphknotens vierzehn Tage nach Therapiebeginn können histologisch keine Residuen des Tumors mehr nachgewiesen werden und es darf von einer vollständigen Remission ausgegangen werden. Die Patientin bleibt in der Folge rezidivfrei. Das homöopathische Mittel Conium (Schierling) kommt in der adjuvanten homöopathischen Tumortherapie und bei vergrößerten Lymphknoten als häufig indiziertes Mittel zur Anwendung.A large-cell B-cell non-Hodgkin Lymphoma (LCBCL) was diagnosed bioptically in a female patient (age 63 years) in one left inguinal lymph node. Immediately after beginning homeopathic treatment with Conium C 30, the lymph node started to show a reduction in size. Two weeks after starting homeopathic therapy, histological examination of the excised lymph node showed no evidence of a residual tumor ­ suggestive of a complete remission. The patient remains disease free until now. The homeopathic remedy Conium (hemlock) is frequently applied for adjuvant homeopathic tumor therapy as well as for the treatment of enlarged lymph nodes.

Conium maculatum intoxication: Literature review and case report on hemlock poisoning.

The aim of this paper is to highlight the symptomatology in three Conium maculatum intoxication incidents, one of which was fatal. A number of studies were reviewed in order to update and summarize the relevant literature on the incidence, sociodemographic variables, method of poisoning, pathophysiology, diagnosis, variables associated with survival and fatality, management, and treatment of C. maculatum intoxication as well as the biosynthesis and biological effects of poison hemlock alkaloids. Results show that hemlock poisoning is relatively rare, although incidence varies in different regions, despite its worldwide distribution. Hemlock poisoning is more common in European and especially Mediterranean countries. The majority of the patients are adult males over 38 years of age. The clinical course of hemlock poisoning includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, rhabdomyolysis, and acute renal failure. The therapeutic management focuses on absorption reduction, close observation for complications, and supportive therapy (especially for respiration). Acute occurrence is severe and life-threatening, but the survival rate is high if treatment is provided promptly. Recovery is rapid, generally taking only a few days.

Identification of Species in the Aromatic Spice Family Apiaceae Using DNA Mini-barcodes.

The species of the aromatic plant family Apiaceae are mainly used as spices and foods, but the family also includes medicinal and some poisonous plant species. Due to the similar chemical compounds or aroma and morphology, the poisonous species are often mistaken for the edible aromatic species. It is therefore imperative to correctly identify the species present at the initial raw stage samples to ensure product safety and efficacy. At the molecular level, plant species can be identified using DNA loci either from nuclear or plastid genome with easily available universal oligonucleotides, a technique called DNA barcoding. However, this is possible when single-species plant material is present but may not work on a mixture of plants species. Another disadvantage is that using universal oligonucleotides is of limited help, especially if the adulterating material is present in low quantities. On the other hand, if using the species-specific oligonucleotides, only single specific adulterating plant material could be detected and, consequently, the unexpected adulterants may go undetected. Therefore, in the current work, four degenerated oligonucleotides from ITS1 and ITS2 regions of the nuclear genome were designed that can bind to a variety of Apiaceae genera only and not to other genera belonging to different plant families. These family-specific oligonucleotides were able to amplify a diagnostic PCR product from 16 Apiaceae species that, upon sequencing, revealed the identity of the plant it was derived from. The size of these products is around 140 bp for ITS1 and approximately 80 bp for the ITS2 region. The size range of the amplified products falls in the category of a desired mini-barcode size to be used for damaged/fragmented DNA and next generation sequencing.

Increased of the hepatocytes and splenocytes apoptosis accompanies clinical improvement and higher survival in mice infected with Trypanosoma cruzi and treated with highly diluted Lycopodium clavatum.

Recent evidence includes apoptosis as a defense against Trypanosoma cruzi infection, which promotes an immune response in the host induced by T cells, type 1, 2 and 17. Currently, there is no medicine completely preventing the progression of this disease. We investigated the immunological and apoptotic effects, morbidity and survival of mice infected with T. cruzi and treated with dynamized homeopathic compounds 13c: Kalium causticum (GCaus), Conium maculatum, (GCon), Lycopodium clavatum (GLy) and 7% alcohol solution (control, vehicle compounds, GCI). There was significant difference in the increase of apoptosis in the treated groups, compared with GCI, which might indicate action of the compounds in these cells. Infected animals treated with Lycopodium clavatum presented better performance compared with other groups. GLy showed a higher amount of hepatocytes and splenocytes undergoing apoptosis, higher number of apoptotic bodies in the liver, predominance of Th1 response, increased TNF-α and decreased IL-6, higher survival, lower morbidity, higher water consumption, body temperature, tendency to higher feed intake and weight gain compared with GCI. Conium maculatum had worse results with increased Th2 response with increased IL-4, worsening of the infection with early mortality of the animals. Together, these data suggest that highly diluted medicines modulate the immune response and apoptosis, affecting the morbidity of animals infected with a highly virulent strain of T. cruzi, being able to minimize the course of infection, providing more alternative approaches in the treatment of Chagas disease.

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

BACKGROUND: Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. OBJECTIVES: We present a case of intravenous poison hemlock injection encountered in the emergency department. CASE REPORT: We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. CONCLUSION: Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

Highly diluted medication reduces tissue parasitism and inflammation in mice infected by Trypanosoma cruzi.

AIM: To evaluate the effects of Kalium causticum, Conium maculatum, and Lycopodium clavatum 13cH in mice infected by Trypanosoma cruzi. MATERIALS AND METHODS: In a blind, controlled, randomized study, 102 male Swiss mice, 8 weeks old, were inoculated with 1400 trypomastigotes of the Y strain of T. cruzi and distributed into the following groups: CI (treated with 7% hydroalcoholic solution), Ca (treated with Kalium causticum 13cH), Co (treated with Conium maculatum 13cH), and Ly (treated with Lycopodium clavatum 13cH). The treatments were performed 48 h before and 48, 96, and 144 h after infection. The medication was repertorized and prepared in 13cH, according to Brazilian Homeopathic Pharmacopoeia. The following parameters were evaluated: infectivity, prepatent period, parasitemia peak, total parasitemia, tissue tropism, inflammatory infiltrate, and survival. Statistical analysis was conduced considering 5% of significance. RESULTS: The prepatent period was greater in the Ly group than in the CI group (p = 0.02). The number of trypomastigotes on the 8th day after infection was lower in the Ca group than in the CI group (p < 0.05). Total parasitemia was significantly lower in the Ca, Co, and Ly groups than in the CI group. On the 12th day after infection, the Ca, Co, and Ly groups had fewer nests and amastigotes/nest in the heart than the CI group (p < 0.05). Decreases in the number of nests and amastigotes in the intestine were observed in the Ly group compared with the CI group (p < 0.05). In the liver (day 12), Ly significantly prevented the formation of inflammatory foci compared with the other groups. In skeletal muscle, Co and Ly decreased the formation of inflammatory foci compared with CI (p < 0.05). Ly afforded greater animal survival compared with CI, Ca, and Co (p < 0.05). The animals in the Co group died prematurely compared with the CI group (p = 0.03). CONCLUSIONS: Ly with 13cH potency had significantly more benefits in the treatment of mice infected with T. cruzi, reducing the number of blood parasites, amastigote nests in tissue, and the number of amastigotes per nest and increasing animal survival.

Polyketide synthases from poison hemlock (Conium maculatum L.).

Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetyl-CoA and three malonyl-CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full-length enzymes by feeding different starter-CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl-CoA as a starter-CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl-CoA and two malonyl-CoAs.

Plant toxins that affect nicotinic acetylcholine receptors: a review.

Plants produce a wide variety of chemical compounds termed secondary metabolites that are not involved in basic metabolism, photosynthesis, or reproduction. These compounds are used as flavors, fragrances, insecticides, dyes, hallucinogens, nutritional supplements, poisons, and pharmaceutical agents. However, in some cases these secondary metabolites found in poisonous plants perturb biological systems. Ingestion of toxins from poisonous plants by grazing livestock often results in large economic losses to the livestock industry. The chemical structures of these compounds are diverse and range from simple, low molecular weight toxins such as oxalate in halogeton to the highly complex norditerpene alkaloids in larkspurs. While the negative effects of plant toxins on people and the impact of plant toxins on livestock producers have been widely publicized, the diversity of these toxins and their potential as new pharmaceutical agents for the treatment of diseases in people and animals has also received widespread interest. Scientists are actively screening plants from all regions of the world for bioactivity and potential pharmaceuticals for the treatment or prevention of many diseases. In this review, we focus the discussion to those plant toxins extensively studied at the USDA Poisonous Plant Research Laboratory that affect the nicotinic acetylcholine receptors including species of Delphinium (Larkspurs), Lupinus (Lupines), Conium (poison hemlock), and Nicotiana (tobaccos).

Prolonged ventilatory failure and flaccid quadriparesis after ingestion of poison hemlock.

INTRODUCTION: A 28-year-old man presented with acute flaccid paralysis and respiratory failure that persisted for 2 weeks after suicidal ingestion of unknown substances. METHODS: Extensive clinical, nerve, laboratory, and neuroimaging testing excluded alternative causes of this neuromuscular syndrome. Prompted by clues provided by family members, liquid chromatography time-of-flight mass spectrometry was used to investigate for the presence of poison hemlock. RESULTS: Testing of the residue in a jar used for the ingestion of a poisonous concoction confirmed the presence of the nicotinic alkaloid coniine. Analysis of patient serum suggested the presence of conhydrine. Concentrations of amitriptyline and diazepam were also found to be supratherapeutic, but only through the first few days of hospitalization. CONCLUSIONS: Herein we describe a case of reversible coma, flaccid quadriparesis, and neuromuscular respiratory failure caused by intentional ingestion of poison hemlock.

Intradermal therapy (mesotherapy) with lymdiaral in chronic venous insufficiency and associated fibrosclerotic edema damage: a pilot study.

OBJECTIVES: Chronic venous insufficiency (CVI) induces alterations that cause fibrosclerotic edema of the subcutaneous tissue. This study examined the effects of a complex naturopathic compound with vasoactive and antiedema activities (Lymdiaral®) administered intradermally. PATIENTS: 40 patients with signs and symptoms of CVI and associated fibrosclerotic edema of the subcutaneous tissue. OUTCOME MEASURES: Efficacy was assessed by using clinical investigation, subjective and objective measures, and ultrasonography performed at baseline and after treatment. RESULTS: Thirty-four patients completed the study; 6 of the original 40 (15%) had stopped for reasons unrelated to study treatment. The treatment was well tolerated. Fifteen adverse reactions were reported among a total of 378 doses administered (3.97%). None of these reactions were severe or required discontinuation of treatment. Subjective symptoms and objective measures improved, and ultrasonography showed statistically significant changes in hypodermal thickness of the medial aspect of the knees. CONCLUSIONS: Its open-label design and small sample size notwithstanding, this study indicates that intradermal therapy, according to the recommendation of the Italian Society of Mesotherapy, may provide a valuable contribution to the treatment of CVI and related fibrosclerotic edema of the subcutaneous tissue by prolonging the local effect of the pharmacologically active compounds. Comparative studies are needed to identify the broader clinical and economic benefits of local therapy compared with other systemic therapies.