amanitins and Mushroom-Poisoning

Amanita poisoning has a high mortality rate. The α-amanitin toxin in Amanita is the main lethal toxin. There is no specific detoxification drug for α-amanitin, and the clinical treatment mainly focuses on symptomatic and supportive therapy. The pathogenesis of α-amanitin mainly includes: α-amanitin can inhibit the activity of RNA polymeraseII in the nucleus, including the inhibition of the largest subunit of RNA polymeraseII, RNApb1, bridge helix, and trigger loop. In addition, α-amanitin acts in vivo through the enterohepatic circulation and transport system. α-Amanitin can cause the cell death. The existing mechanisms of cell damage mainly focus on apoptosis, oxidative stress, and autophagy. In addition to the pathogenic mechanism, α-amanitin also has a role in cancer treatment, which is the focus of current research. The mechanism of action of α-amanitin on the body is still being explored.

Topics: Alpha-Amanitin; Amanita; Amanitins; Humans; Mushroom Poisoning; RNA

Among the toxic metabolites of the fungal world, those that, due to their strong biological effect, can seriously (even fatally) damage the life processes of humans (and certain groups of animals) stand out. Amatoxin-containing mushrooms and the poisonings caused by them stand out from the higher fungi, the mushrooms. There are already historical data and records about such poisonings, but scientific research on the responsible molecules began in the middle of the last century. The goals of this review work are as follows: presentation of the cosmopolitan mushroom species that produce amanitins (which are known from certain genera of four mushroom families), an overview of the chemical structure and specific properties of amanitins, a summary of the analytical methods applicable to them, a presentation of the "medical history" of poisonings, and a summary of the therapeutic methods used so far. The main responsible molecules (the amanitins) are bicyclic octapeptides, whose structure is characterized by an outer loop and an inner loop (bridge). It follows from the unusual properties of amanitins, especially their extreme stability (against heat, the acidic pH of the medium, and their resistance to human, and animal, digestive enzymes), that they are absorbed almost without hindrance and quickly transported to our vital organs. Adding to the problems is that accidental consumption causes no noticeable symptoms for a few hours (or even 24-36 h) after consumption, but the toxins already damage the metabolism of the target organs and the synthesis of nucleic acid and proteins. The biochemical catastrophe of the cells causes irreversible structural changes, which lead to necrotic damage (in the liver and kidneys) and death. The scientific topicality of the review is due to the recent publication of new data on the probable antidote molecule (ICR: indocyanine green) against amanitins. Further research can provide a new foundation for the therapeutic treatment of poisonings, and the toxicological situation, which currently still poses a deadly threat, could even be tamed into a controllable problem. We also draw attention to the review conclusions, as well as the mycological and social tasks related to amanitin poisonings (prevention of poisonings).

Topics: Agaricales; Amanitins; Animals; Antidotes; Humans; Mushroom Poisoning; Poisons

We searched MEDLINE and Embase for case series and case reports that described patient outcomes after poisoning with amanitin-containing. We included 131 publications describing a total of 877 unique cases. The overall survival rate of all patients was 84%. Patients receiving only supportive care had a survival rate of 59%. The use of SIL or PEN was associated with a 90% (OR 6.40 [3.14-13.04]) and 89% (OR 5.24 [2.87-9.56]) survival rate, respectively. NAC/SIL combination therapy was associated with 85% survival rate (OR 3.85 [2.04, 7.25]). NAC/PEN/SIL treatment group had a survival rate of 76% (OR 2.11 [1.25, 3.57]). Due to the limited number of cases, the use of NAC alone could not be evaluated. Additional analyses in 'proven cases' (amanitin detected), 'probable cases' (mushroom identified by mycologist), and 'possible cases' (neither amanitin detected nor mushroom identified) showed comparable results, but the results did not reach statistical significance. Transplantation-free survivors had significantly lower peak values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total serum bilirubin (TSB), and international normalized ratio (INR) compared to liver transplantation survivors and patients with fatal outcomes. Higher peak PSS was associated with increased mortality.. Based on data available, no statistical differences could be observed for the effects of NAC, PEN or SIL in proven poisonings with amanitin-containing mushrooms. However, monotherapy with SIL or PEN and combination therapy with NAC/SIL appear to be associated with higher survival rates compared to supportive care alone. AST, ALT, TSB, and INR values are possible predictors of potentially fatal outcomes.

Topics: Acetylcysteine; Alanine Transaminase; Amanita; Amanitins; Humans; Mushroom Poisoning; Penicillin G; Silybin

Acute poisoning could result in hepatic dysfunction which is potentially life threatening. We reviewed three cases of poison-induced liver injury with gastrointestinal disorder on admission. Two cases were poisoned by mushroom α-Amanitin while the other was poisoned by acetaminophen (APAP). They were cured under the close monitor of laboratory examinations and other supportive therapies, as well as the off-label medication of etanercept, a kind of tumor necrosis factor-α (TNF-α) blockers with written informed consent. Among them, case1 was given the first dose doubling of TNF-α blockers for higher liver enzyme levels. There is a lack of effective and safe treatments for poison-induced liver injury. TNF-α has been proved to play an important role in the aggravation of liver injury and the start-up of inflammatory cascade reaction. Therapy with TNF-α blockers shown potential therapeutic efficacy in hepatic dysfunction by some researches. Anyway, no strong recommendation could be drawn from these small sample size studies. On the other side, TNF-α could also mediate an opposing effect for hepatocytes since the hepatic toxicity of TNF-α blockers has generated attentions. The safety for the off-label medication of TNF-α blockers in liver injury, however, still lacks strong evidences. More experimental and clinical researches are needed to focus on potential mechanisms.

Topics: Acetaminophen; Amanitins; Chemical and Drug Induced Liver Injury, Chronic; Humans; Liver; Mushroom Poisoning; Tumor Necrosis Factor Inhibitors

The consumption of mushrooms has become increasingly popular, partly due to their nutritional and medicinal properties. This has increased the risk of confusion during picking, and thus of intoxication. In France, about 1300 cases of intoxication are observed each year, with deaths being mostly attributed to

Topics: Amanitins; Animals; Humans; Mushroom Poisoning

Amanita neoovoidea (genus Amanita Pers.) poisoning leads to acute renal failure. Here, we present seven case reports of acute renal failure with acute hepatic failure due to ingestion of A. neoovoidea. Clinical manifestations included gastrointestinal symptoms 1-72 h after ingestion; elevation of renal parameters and blood uric acid, blood urea nitrogen, and creatinine levels; a few abnormal hepatic parameters, primarily albumin decrease and alanine aminotransferase increase; and elevation of zymogram parameters such as cholinesterase and lactate dehydrogenase. To determine whether the hepatic/renal lesions were caused by amanitins, we analyzed the blood and urine samples of patients and specimens of poisonous mushrooms. Morphological and molecular biological analyses indicated that the mushroom was A. neoovoidea. However, no amatoxins and phallotoxins were detected in its basidiomata.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Amanita; Amanitins; Blood Urea Nitrogen; China; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Male; Middle Aged; Mushroom Poisoning; Uric Acid

Amatoxins are produced primarily by 3 species of mushrooms: Amanita, Lepiota, and Galerina. Because amatoxin poisonings are increasing, the objective of this review was to identify all amatoxin-containing mushroom species, present a toxidromic approach to earlier diagnoses, and compare the efficacies and outcomes of therapies. To meet these objectives, Internet search engines were queried with keywords to select peer-reviewed scientific articles on amatoxin-containing mushroom poisoning and management. Descriptive epidemiological analyses have documented that most mushroom poisonings are caused by unknown mushrooms, and most fatal mushroom poisonings are caused by amatoxin-containing mushrooms. Amanita species cause more fatal mushroom poisonings than other amatoxin-containing species, such as Galerina and Lepiota. Amanita phalloides is responsible for most fatalities, followed by Amanita virosa and Amanita verna. The most frequently reported fatal Lepiota ingestions are due to Lepiota brunneoincarnata, and the most frequently reported fatal Galerina species ingestions are due to Galerina marginata. With the exception of liver transplantation, the current treatment strategies for amatoxin poisoning are all supportive and have not been subjected to rigorous efficacy testing in randomized controlled trials. All patients with symptoms of late-appearing gastrointestinal toxicity with or without false recovery or quiescent periods preceding acute liver insufficiency should be referred to centers providing liver transplantation. Patients with amatoxin-induced acute liver insufficiency that does not progress to liver failure will have a more favorable survival profile with supportive care than patients with amatoxin-induced acute liver failure, about half of whom will require liver transplantation.

Topics: Agaricales; Amanita; Amanitins; Hepatic Insufficiency; Humans; Liver Failure, Acute; Liver Transplantation; Mushroom Poisoning

Amanita phalloides poisoning with a high mortality is a serious health problem in the world. The typical clinical manifestations are usually characterized by the absence of any symptoms followed by severe gastrointestinal disorders and acute liver failure. Inhibition of RNA polymeraseII (RNAP II) activity, apoptosis, and oxidative stress are considered as the major mechanism of amatoxins intoxication. The current treatment measures mainly include prevention of amatoxins absorption, elimination of absorbed amatoxins, potential antidotes therapy, and liver transplantation. Nevertheless, there are no widely accepted treatment criteria for Amanita phalloides poisoning. This paper will focus on the treatment measures based on the previous studies and provide the currently available information for clinicians.

Topics: Acetylcysteine; Amanita; Amanitins; Antidotes; Bile Ducts; Charcoal; Diuresis; Gastric Lavage; Humans; Liver; Liver Failure, Acute; Liver Transplantation; Mushroom Poisoning; Penicillin G; Silymarin

Topics: Acute Disease; Adult; Aged; Amanitins; Female; Glasgow Coma Scale; Hepatic Encephalopathy; Hong Kong; Humans; Liver Transplantation; Male; Middle Aged; Mushroom Poisoning

A shortcut review was carried out to establish whether silibinin is better than conservative management at reducing liver transplantation and death after poisoning with amatoxin-containing mushrooms. Thirty-eight papers were found in Medline and 86 in EMBASE using the reported searches. Of these, five presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the evidence is limited, but given the lack of alternative treatments in patients with suspected amatoxin-containing mushroom poisoning and the relatively few adverse effects, silibinin should be considered in some patients.

Topics: Amanitins; Antioxidants; Evidence-Based Emergency Medicine; Humans; Mushroom Poisoning; Silybin; Silymarin

Death cap (Amanita phalloides) is commonly found and is one of the five most toxic fungi in Denmark. Toxicity is due to amatoxin, and poisoning is a serious medical condition, causing organ failure with potential fatal outcome. Acknowledgement and clarification of exposure, symptomatic and focused treatment is of primary importance. No data from randomised, controlled trials on management exists, and there is not international consensus on treatment regime. We present amatoxin-case contacts to the Danish Poison Centre from 2006-2012 and summarize current knowledge and Danish recommendations in amatoxin poisoning management.

Topics: Amanita; Amanitins; Denmark; Fungal Proteins; Humans; Mushroom Poisoning; Time Factors

Topics: Acetylcysteine; Amanita; Amanitins; Bile; Blood Component Removal; Charcoal; Chromatography, High Pressure Liquid; Drainage; Gastric Lavage; Humans; Japan; Laxatives; Liver Transplantation; Mushroom Poisoning; Penicillin G; Silybin; Silymarin

Topics: Acetylcysteine; Adult; Amanita; Amanitins; Cause of Death; Combined Modality Therapy; Critical Care; Diagnosis, Differential; Hepatic Encephalopathy; Humans; Liver Function Tests; Liver Transplantation; Male; Mushroom Poisoning; Prognosis; Silybin; Silymarin

Diagnosis and management of Amanita mushroom poisoning is a challenging problem for physicians across the United States. With 5902 mushroom exposures and two resultant deaths directly linked to Amanita ingestion in 2009, it is difficult for physicians to determine which patients are at risk for lethal toxicity. Identification of amatoxin poisoning can prove to be difficult due to delay in onset of symptoms and difficulty with identification of mushrooms. Consequently, it is difficult for the Emergency Physician to determine proper disposition. Further, treatment options are controversial.. To review current data to help health care providers effectively identify and treat potentially deadly Amanita mushroom ingestions.. We present two cases of Amanita mushroom ingestion in the northeastern United States treated with N-acetylcysteine, high-dose penicillin, cimetidine, and silibinin, a semi-purified fraction of milk thistle-derived silymarin, as part of their treatment regimen. The mushroom species was identified by a consultant as Amanita Ocreata.. We present the successful treatment of 2 patients who ingested what we believe to be an Amanita species never before identified in the northeastern United States.

Topics: Aged; Amanita; Amanitins; Antioxidants; Female; Humans; Male; Middle Aged; Mushroom Poisoning; Treatment Outcome

More than 90% of all fatal mushroom poisonings worldwide are due to amatoxin containing species that grow abundantly in Europe, South Asia, and the Indian subcontinent. Many cases have also been reported in North America. Initial symptoms of abdominal cramps, vomiting, and a severe cholera-like diarrhea generally do not manifest until at least six to eight hours following ingestion and can be followed by renal and hepatic failure. Outcomes range from complete recovery to fulminant organ failure and death which can sometimes be averted by liver transplant. There are no controlled clinical studies available due to ethical reasons, but uncontrolled trials and case reports describe successful treatment with intravenous silibinin (Legalon® SIL). In nearly 1,500 documented cases, the overall mortality in patients treated with Legalon® SIL is less than 10% in comparison to more than 20% when using penicillin or a combination of silibinin and penicillin. Silibinin, a proven antioxidative and anti-inflammatory acting flavonolignan isolated from milk thistle extracts, has been shown to interact with specific hepatic transport proteins blocking cellular amatoxin re-uptake and thus interrupting enterohepatic circulation of the toxin. The addition of intravenous silibinin to aggressive intravenous fluid management serves to arrest and allow reversal of the manifestation of fulminant hepatic failure, even in severely poisoned patients. These findings together with the available clinical experience justify the use of silibinin as Legalon® SIL in Amanita poisoning cases.

Topics: Amanitins; Animals; Antidotes; Chemical and Drug Induced Liver Injury; Humans; Molecular Structure; Mushroom Poisoning; Silymarin; Tissue Distribution; Treatment Outcome

Silibinin is the most active component of a complex of flavonoids -silymarin contained in fruit milk thistle (Sylibum marianum). Its mechanism of action is complex and highly beneficial in protecting hepatocytes. On the one hand this compound blocks the penetration of various toxins (for example amanitin) into the hepatocytes not allowing in this way for the cell death and on the other hand, it prevents apoptosis through intracellular. It protects the liver from oxidative intracellular free radicals by increasing the activity of enzyme superoxide dismutase and peroxidase, as well as by increasing the concentration of glutathione and the activity of the peroxidase. Silibinin strengthens and stabilizes the cell membranes, inhibits the synthesis of prostaglandins associated with the lipid peroxidation and promotes regeneration of liver through the stimulation of protein synthesis and effect on the production of new hepatocytes. A particularly interesting topic from the perspective of a toxicologist is the application of silibinin in Amanita phalloides poisoning. Clinical trials conducted in this respect are very encouraging. The other beneficial application of silibinin is in therapy of the alcoholic liver cirrhosis. The evidence shows that the use of silymarin leads to a significant reduction in liver-related mortality and even reduction in the number of patients with encephalopathy in the course of the disease. Application of silibinin goes beyond liver disease and expands in the direction of cancer and even diabetes. What is interesting is the fact, that the substance of herbal origin occurring in the environment is so strong, favorable, beneficial and multidirectional. Science has contributed to improving the bioavailability of silibinin thus making it more effective.

Topics: Amanita; Amanitins; Chemical and Drug Induced Liver Injury; Hepatocytes; Humans; Lipid Peroxidation; Liver Diseases; Liver Regeneration; Mushroom Poisoning; Peroxidases; Prostaglandins; Protective Agents; Silybin; Silymarin; Superoxide Dismutase

Topics: Agaricales; Amanitins; Cyanides; Humans; Japan; Mushroom Poisoning; Peptides, Cyclic

Mushrooms are ubiquitous in nature. They are an important source of nutrition; however, certain varieties contain chemicals that can be highly toxic to humans. Industrially cultivated mushrooms are historically very safe, but foraging for mushrooms or accidental ingestion of mushrooms in the environment can result in serious illness and death. The emergency department is the most common site of presentation for patients suffering from acute mushroom poisoning. Although recognition can be facilitated by identification of a characteristic toxidrome, the presenting manifestations can be variable and have considerable overlap with more common and generally benign clinical syndromes. The goal of this two-part article is to review the knowledge base on this subject and provide information that will assist the clinician in the early consideration, diagnosis and treatment of mushroom poisoning. Part I, presented in this issue of the Journal, reviews the epidemiology and demographics of mushroom poisoning, the physical characteristics of the most toxic varieties, the classification of the toxic species, and an overview of the cyclopeptide-containing mushroom class. Part II, to be published in the next issue of the Journal, will be focused on the presentation of the other classes of toxic mushrooms along with an up-to-date review of the most recently identified poisonous varieties.

Topics: Agaricales; Amanita; Amanitins; Child, Preschool; Humans; Mushroom Poisoning; Mycotoxins

This paper examines the biology and medical consequences of ingesting the potentially lethal poisonous mushroom, Amanita virosa, the Destroying Angel. The fungus, its structure, distribution and toxic components are described. Symptoms of human poisoning by A. virosa are described, following the order of Homeopathic Repertories. Laboratory values for comparison with normal values of haematology, biochemistry and urine analyses are given.

Topics: Amanita; Amanitins; Humans; Materia Medica; Mushroom Poisoning; Phalloidine; Risk Factors

Among fungal toxins causing organ damage in the human body, amatoxins and orellanine remain exceptional. Amatoxins, a group of bicyclic octapeptides occurring in some Amanita, Galerina and Lepiota species, induce deficient protein synthesis resulting in cell death, but might also exert toxicity through inducing apoptosis. Target organs are intestinal mucosa, liver and kidneys. Poisoning will result in dehydration and electrolyte derangement, liver necrosis and possibly kidney damage. In established poisoning the mainstay of treatment is optimum symptomatic and supportive care. No specific treatment is available, but some pharmaceuticals, like silibinin, benzylpenicillin and acetylcysteine, might have a role in limiting the extent of hepatic damage. Orellanine is a nephrotoxic bipyridine N-oxide found in some Cortinarius species. Its mechanism of action is not fully understood, but it has been shown to inhibit protein synthesis and to generate free oxygen radicals. As early symptoms often are lacking or vague, poisoning may initially be overlooked or misinterpreted and the patients usually present with established renal damage. Supportive care is the only therapeutic option. Tricholoma equestre might contain a myotoxin and repeated ingestion may cause significant rhabdomyolysis. Ingestion of Amanita smithiana and A. proxima has been reported to result in kidney damage. Gyromitrin, a toxic compound that is converted to hydrazines in the stomach, occurs in some Gyromitra species. It is mainly neurotoxic, but may also induce moderate hepatic damage and haemolysis.

Topics: 2,2'-Dipyridyl; Acetaldehyde; Amanitins; Basidiomycota; Humans; Kidney Diseases; Mushroom Poisoning; Mycotoxins; Rhabdomyolysis

Amatoxin poisoning is a medical emergency characterized by a long incubation time lag, gastrointestinal and hepatotoxic phases, coma, and death. This mushroom intoxication is ascribed to 35 amatoxin-containing species belonging to three genera: Amanita, Galerina, and Lepiota. The major amatoxins, the alpha-, beta-, and gamma-amanitins, are bicyclic octapeptide derivatives that damage the liver and kidney via irreversible binding to RNA polymerase II.. The mycology and clinical syndrome of amatoxin poisoning are reviewed. Clinical data from 2108 hospitalized amatoxin poisoning exposures as reported in the medical literature from North America and Europe over the last 20 years were compiled. Preliminary medical care, supportive measures, specific treatments used singly or in combination, and liver transplantation were characterized. Specific treatments consisted of detoxication procedures (e.g., toxin removal from bile and urine, and extracorporeal purification) and administration of drugs. Chemotherapy included benzylpenicillin or other beta-lactam antibiotics, silymarin complex, thioctic acid, antioxidant drugs, hormones and steroids administered singly, or more usually, in combination. Supportive measures alone and 10 specific treatment regimens were analyzed relative to mortality.. Benzylpenicillin (Penicillin G) alone and in association was the mostfrequently utilized chemotherapy but showed little efficacy. No benefit was found for the use of thioctic acid or steroids. Chi-square statistical comparison of survivors and dead vs. treated individuals supported silybin, administered either as mono-chemotherapy or in drug combination and N-acetylcysteine as mono-chemotherapy as the most effective therapeutic modes. Future clinical research should focus on confirming the efficacy of silybin, N-acetylcysteine, and detoxication procedures.

Topics: Agaricales; Amanitins; Animals; Chemical and Drug Induced Liver Injury; Emergency Medical Services; Humans; Liver Transplantation; Mushroom Poisoning; Retrospective Studies

Topics: Amanita; Amanitins; Critical Care; Diagnosis, Differential; Humans; Metabolic Clearance Rate; Mushroom Poisoning; Prognosis

The most poisonous mushroom toxins are produced by Amanita phalloides (death cap). The occurrence and chemistry of three groups of toxins (amatoxins, phallotoxins and virotoxins) are summarized. The concentration and distribution of toxins in certain species are variable, with the young fruit body containing lower, and the well-developed fungus higher concentrations, but there is a high variability among specimens collected in the same region. Regarding phallotoxins, the volva (the ring) is the most poisonous. The most important biochemical effect of amatoxins is the inhibition of RNA polymerases (especially polymerase II). This interaction leads to a tight complex and the inhibition is of a non-competitive type. Non-mammalian polymerases show little sensitivity to amanitins. The amatoxins cause necrosis of the liver, also partly in the kidney, with the cellular changes causing the fragmentation and segregation of all nuclear components. Various groups of somatic cells of emanation resistance have been isolated, including from a mutant of Drosophila melanogaster. The phallotoxins stimulate the polymerization of G-actin and stabilize the F-actin filaments. The interaction of phallotoxins occurs via the small, 15-membered ring, on the left side of the spatial formula. The symptoms of human poisoning and the changes in toxin concentrations in different organs are summarized. Conventional therapy includes: (1) stabilization of patient's condition with the correction of hypoglycaemia and electrolytes; (2) decontamination; and (3) chemotherapy with different compounds. Finally, certain antagonists and protective compounds are reviewed, bearing in mind that today these have more of a theoretical than a practical role.

Topics: Amanita; Amanitins; Animals; Humans; Models, Molecular; Molecular Structure; Mushroom Poisoning; Peptides, Cyclic

Hepatotoxic mushroom poisoning (due to Amanita, Lepiota and Galerina species) may be considered as a real medical emergency, since an early diagnosis and immediate treatment are required for a successful outcome. In this review the physio-pathological features and the clinical picture of amatoxin poisonings are described as the basis for diagnosis and therapeutic decisions. The treatment schedule proposed is analyzed in some points: Symptomatic and supportive measures, toxin removal and extraction procedures, and the possibility of using antidotes. Some parameters with prognostic significance are commented on. Finally, the mortality rate and its evolution throughout the present century is also considered.

Topics: Amanitins; Combined Modality Therapy; Humans; Mushroom Poisoning; Prognosis

Poisoning with mushrooms of the genus Amanita, members of which occur frequently in both North America and Europe, accounts for a significant number of deaths annually. Liver damage is the main clinical feature and death rates are variously reported to be from 11.3% to 51.3% of patients. The amount of mushroom ingested appears to be the main prognostic indicator and a fatal outcome appears inevitable if a large amount is eaten. In sublethal exposures, supportive therapy seems effective; when definitive treatment is considered, hyperbaric oxygen, penicillin and silymarin are indicated in conjunction with careful management of blood glucose concentration. Charcoal hemoperfusion, forced diuresis, hyperbaric oxygen, and thioctic acid may also be considered, although these treatment modalities are not clearly associated with increased survival.

Topics: Amanitins; Animals; Blood Glucose; Charcoal; Chemical and Drug Induced Liver Injury; Diuresis; Glucose; Hemoperfusion; Humans; Mushroom Poisoning; Silymarin; Thioctic Acid

Topics: Amanita; Amanitins; Combined Modality Therapy; Digestive System; Humans; Kidney; Liver; Mushroom Poisoning; Penicillins; Prognosis; Silymarin; Spain; Species Specificity; Therapeutic Irrigation; Thioctic Acid

The phalloidian toxins are very complex. The classification proposed by Wieland distinguishes between the various amatoxins and phallotoxins. The authors study successively: Methods of isolation, the general structure and chemical composition, their localization and concentration in mushrooms. This is an analytical study of the phallotoxins and amadoxins. Various experimental intoxication protocols using total extracts of the toxins purified with different doses and different animals have revealed the main signs of experimental intoxication with phallotoxins. This is characterized especially by hepatic and renal lesions. The phallotoxins have a more specific action on the cell membrane and metabolism. The amatoxins have a more specific action on the cell nucleus and protein synthesis. The action on DNA dependent RNA polymerases is particularly characteristic.

Topics: Amanita; Amanitins; Animals; Humans; Mushroom Poisoning

Much progress in the areas of identification of active components and elucidation of the toxic mechanisms for the principal poisonous mushrooms has been made in the past decade. This affords a more rational approach to therapeutic management which has consequently resulted in a decrease in the morbidity and mortality associated with these species. However, the effectiveness of a large number of adjuvants for Amanita phalloides poisoning still needs critical laboratory evaluation. The current status of knowledge concerning the toxic potential and contituents of many mushroom species, including the gastroenteric irritants, is inadequate. The problem of geographic variation or genetic strain in the concentration of toxins of many species also requires further investigation. The recent awareness and interest in the pharmacology and toxicology of uncultivated mushrooms in North America and Great Britain should encourage continued active research.

Topics: Amanitins; Animals; Basidiomycota; Disulfiram; Hallucinations; Humans; Irritants; Mushroom Poisoning; Parasympathetic Nervous System; Psilocybin

The authors describe frequency and importance of poisoning by Amanita phalloides. There are demonstrated the different toxins and their biochemical properties. The typical clinical symptoms of the intoxication by Amanita phalloides with vourse in two phases (1. gastrointestinal phase, 2. hepatonephrotic phase) are shown. The possibilities of diagnostic and differentialdiagnostic and the problems of therapy are discussed. It is pointed out, that in a modern treatment there must be given Penicillin-G-Natrium in high dosage as early as possible, also in cases of questionableness. Hemodialysis is only of effect till 40 hours after ingestion of Amanita.

Topics: Amanita; Amanitins; Blood Coagulation Disorders; Child; Diagnosis, Differential; Female; Hepatic Encephalopathy; Humans; Mushroom Poisoning; Penicillin G

On the basis of experimental and clinical results evidence accumulates that supportive therapy is still the milestone in the therapy of death cap poisoning. Today the letality is 20%. The main cause of the intoxication are the amatoxines which inhibit DNA dependent RNA Polymerase II or B. Parts of the supportive therapy are: diuresis with 150--200 ml urin/hour, careful corrections of disturbances in electrolyte and acid-base-metabolism, oral administration of charcoal and oral gut sterilization. In spite of a multitude of experimental and clinical reports on the effectivity of Penicillin G, thiocticacid and steroids there are no controlled studies to demonstrate the advantage of one regimen over the other. The time course of resorption and excretion of amatoxines clearly shows that hemoperfusion and/or hemodialysis are only of value if applied within the first 24 hours after poisoning. At this time neither anamnestic nor biochemical data give any clues to the probable course of the disease. Heterologous baboon liver perfusion may be lifesaving in coma hepaticum grade IV, but the small amount of cases so far does not yet allow any comments on its effectivity.

Topics: Amanita; Amanitins; Animals; Hemoperfusion; Hepatic Encephalopathy; Humans; Liver; Mushroom Poisoning; Papio; Perfusion; Renal Dialysis; Time

Topics: Amanitins; Bile; Blood Coagulation Disorders; Charcoal; Enterohepatic Circulation; Filtration; Gastric Lavage; Hemoperfusion; Humans; Intestinal Secretions; Liver; Liver Regeneration; Mushroom Poisoning; Renal Dialysis; RNA Polymerase II; RNA Polymerase III; RNA, Messenger; Silymarin; Thioctic Acid; Time; Transcription, Genetic

Topics: Amanitins; Humans; Liver; Mushroom Poisoning

Approximately 70%∼90% of mushroom poisoning deaths are caused by the class of mushroom toxins known as amatoxins. However, the rapid elimination of amatoxins from plasma within 48 h after mushroom ingestion limits the practical value of plasma amatoxin analysis as a diagnostic indicator of Amanita mushroom poisoning. To increase the positive detection rate and extend the detection window of amatoxin poisoning, we developed a new method to detect protein-bound α-amanitin based on the hypothesis that RNAP II-bound α-amanitin released from the tissue into the plasma could be degraded by trypsin hydrolysis and then detected by conventional liquid chromatography-mass spectrometry (LC‒MS). Toxicokinetic studies on mice intraperitoneally injected with 0.33 mg/kg α-amanitin were conducted to obtain and compare the concentration trends, detection rates, and detection windows of both free α-amanitin and protein-bound α-amanitin. By comparing detection results with and without trypsin hydrolysis in the liver and plasma of α-amanitin-poisoned mice, we verified the credibility of this method and the existence of protein-bound α-amanitin in plasma. Under the optimized trypsin hydrolysis conditions, we obtained a time-dependent trend of protein-bound α-amanitin in mouse plasma at 1-12 days postexposure. In contrast to the short detection window (0-4 h) of free α-amanitin in mouse plasma, the detection window of protein-bound α-amanitin was extended to 10 days postexposure, with a total detection rate of 53.33%, ranging from the limit of detection to 23.94 μg/L. In conclusion, protein-bound α-amanitin had a higher positive detection rate and a longer detection window than free α-amanitin in mice.

Topics: Alpha-Amanitin; Amanita; Amanitins; Animals; Chromatography, Liquid; Mice; Mushroom Poisoning; Trypsin

Topics: Amanitins; Humans; Liver; Mushroom Poisoning

A 60-year-old man presented with acute gastroenteritis, hypovolemic shock, acute renal failure (BUN/Cr, 56.7/4.24 mg/dl), and aspiration pneumonia. The previous day, he ingested 30 caps of mushrooms of an unknown species. The patient was treated with a massive intravenous infusion, renal replacement therapy, and antimicrobial agents. Late-onset mild liver injury peaked on day 11 (AST/ALT, 62/67 IU/l). Acute renal failure improved once before worsening, with the worst symptoms on day 19 (BUN/Cr, 99/6.61 mg/dl). Thereafter, the patient showed gradual improvement, and renal replacement therapy was discontinued on day 23. His general condition improved fully and he was transferred to another hospital for rehabilitation on day 47. The mushrooms were later identified as Galerina sulciceps by the Basic Local Alignment Search Tool, and toxicologic analysis using liquid chromatography-tandem mass spectrometry revealed an average of 85 ppm α-amanitin and 330 ppm β-amanitin in the tissue of the mushrooms brought in by the patient's family. Galerina sulciceps is distributed mainly in tropical and subtropical regions of Southeast Asia and had never been identified before in Japan. The heat of fermentation generated by the thick layer of wood chips on the ground or global warming may have contributed to its growth in Japan. Interestingly, our patient did not have liver dysfunction, which is one main and typical amatoxin poisoning symptom. Variation in clinical presentation may be attributed to the different ratios of α-amanitin to β-amanitin in different mushroom species.

Topics: Acute Kidney Injury; Agaricales; Alpha-Amanitin; Amanitins; Humans; Japan; Male; Middle Aged; Mushroom Poisoning

Topics: Amanita; Amanitins; Humans; Mushroom Poisoning

About 95% of fatal mushroom poisonings worldwide are caused by amatoxins and phallotoxins mostly produced by species of Amanita, Galerina, and Lepiota. The genus Lepiota is supposed to include a high number of species producing amatoxins. In this study, we investigated 16 species of Lepiota based on 48 recently collected specimens for the presence of amatoxins by liquid chromatography coupled to a diode-array detector and mass spectrometry (UHPLC-QTOF-MS/MS). By comparing the retention times, UV absorptions, and diagnostic MS fragment ions with data obtained from the benchmark species Amanita phalloides, we detected α-amanitin and γ-amanitin in Lepiota subincarnata, α-amanitin and amaninamide in Lepiota brunneoincarnata, and β-amanitin and α-amanitin in Lepiota elaiophylla. Phallotoxins have not been detected any of these species. Two possibly undescribed amatoxin derivatives were found in Lepiota boudieri and L. elaiophylla, as well as one further non-amatoxin compound in one specimen of L. cf. boudieri. These compounds might be used to differentiate L. elaiophylla from L. xanthophylla and species within the L. boudieri species complex. No amatoxins were detected in L. aspera, L. castanea, L. clypeolaria, L. cristata, L. erminea, L. felina, L. fuscovinacea, L. lilacea, L. magnispora, L. oreadiformis, L. pseudolilacea, L. sp. (SeSa 5), and L. subalba. By combining the occurrence data of amatoxins with a phylogenetic analysis, a monophyletic group of amatoxin containing species of Lepiota is evident. These chemotaxonomic results highlight the relevance of systematic relationships for the occurrence of amatoxins and expand our knowledge about the toxicity of species of Lepiota.

Topics: Agaricales; Amanitins; Mushroom Poisoning; Phylogeny; Tandem Mass Spectrometry

Topics: Amanita; Amanitins; Enterohepatic Circulation; Kinetics; Mushroom Poisoning

To describe the rapid diagnosis, treatment, and clinical course of a dog that ingested an amanitin-containing mushroom.. A 2-month-old female intact Australian Shepherd presented with diarrhea and vomiting, along with a possible mushroom exposure. Upon presentation, the dog's urine was collected and tested positive by a point-of-care rapid diagnostic test specific for detecting amanitins, the causative agents of amatoxicosis.. This is the first reported case of amatoxicosis that was diagnosed using a point-of-care test prior to starting treatment. An early diagnosis helps to guide early treatment decisions in this frequently fatal toxicosis.

Topics: Amanitins; Animals; Australia; Dog Diseases; Dogs; Early Diagnosis; Female; Mushroom Poisoning; Point-of-Care Testing; Urinalysis

Pseudosperma species are widely distributed worldwide. Many of them cause poisoning incidents every year, and the toxin responsible for poisoning is muscarine, which could stimulate the parasympathetic nervous system. This study established a method using multiwalled carbon nanotube purification and liquid chromatography-tandem mass spectrometry for the targeted screening of mushroom toxins (muscarine, isoxazole derivatives, tryptamine alkaloids, three amatoxins and three phallotoxins) from Pseudosperma umbrinellum, a common poisonous mushroom distributed in north and northwestern China. Surprisingly, in addition to muscarine, phalloidin was also detected in P. umbrinellum, and the contents were 3022.2 ± 604.4 to 4002.3 ± 804.6 mg/kg (k = 2; p = 95%) muscarine and 5.9 ± 1.2 to 9.3 ± 1.8 mg/kg (k = 2; p = 95%) phalloidin.

Topics: Agaricales; Amanitins; Muscarine; Mushroom Poisoning; Phalloidine

The paper presents results of AI diagnostics and treatment across the period of 2004-2020 pointing to the efficacy of two particular protocols.. Quantitative determination of amanitins in blood (ATOs) and urine (ATOu) performed by the original ELISA kit, indicated upon mycological history and clinical symptoms of poisoning. ATOu positive cases were recommended our protocol; ATOu negative results excluded amanitin poisoning.. out of 2876 fungal poisonings registered in Slovakia during the subjected period, were 698 AI suspected cases. In 557 of them, was AI reliably excluded, in 141 confirmed. Urinary ATOu correlated with the severity of poisoning in the range of 6-47 h after mushroom ingestion, without false negativity. Serum ATOs had no diagnostic value. 129 patients with confirmed AI received full treatment protocol with antidotes of penicillin plus silibinin. In this group died two patients of acute kidney injury in the early stages of poisoning and 127 patients were recovered. Silibinin without penicillin was used in 12 patients. One of them undergone liver transplantation and four patients died of fulminant liver failure, respectively intracranial hemorrhage. Treatment failure in the PNC + silibinin protocol was 1.5 % (2 of 127 patients), silibinin alone being 41.7 % (5 of 12 patients, p = 0.00058).. Early diagnostics of amanitin intoxication based on mycological and clinical history and subsequent determination of urinary amanitin levels (ATOu) allows early initiation of treatment. The use of treatment protocol with antidotes of PNC and silibinin is of high therapeutic efficacy. The omission of PNC from the treatment protocol significantly worsens patients' prognosis.

Topics: Amanita; Amanitins; Antidotes; Humans; Mushroom Poisoning; Penicillins; Silybin; Slovakia

Topics: Acetylcysteine; Amanitins; Humans; Mushroom Poisoning

Topics: Acetylcysteine; Amanitins; Humans; Mushroom Poisoning

Mushroom toxicity is the main branch of foodborne poisoning, and liver damage caused by amatoxin poisoning accounts for more than 90 % of deaths due to mushroom poisoning. Alpha-amatoxin (α-AMA) has been considered the primary toxin from amatoxin-containing mushrooms, which is responsible for hepatotoxicity and death. However, the mechanism underlying liver failure due to α-AMA remains unclear. This study constructed animal and cell models. In the animal experiments, we investigated liver injury in BALB/c mice at different time points after α-AMA treatment, and explored the process of inflammatory infiltration using immunohistochemistry and western blotting. Then, a metabonomics method based on gas chromatography mass spectrometry (GCMS) was established to study the effect of α-AMA on liver metabonomics. The results showed a significant difference in liver metabolism between the exposed and control mice groups that coincided with pathological and biochemical indicators. Moreover, 20 metabolites and 4 metabolic pathways related to its mechanism of action were identified, which suggested that energy disorders related to mitochondrial dysfunction may be one of the causes of death. The significant changes of trehalose and the fluctuation of LC3-II and sqstm1 p62 protein levels indicated that autophagy was also involved in the damage process, suggesting that autophagy may participate in the clearance process of damaged mitochondria after poisoning. Then, we constructed an α-AMA-induced human normal liver cells (L-02 cells) injury model. The above hypothesis was further verified by detecting cell necrosis, mitochondrial reactive oxygen species (mtROS), mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (Δψ m), and cellular ATP level. Collectively, our results serve as direct evidence of elevated in vivo hepatic mitochondrial metabolism in α-AMA-exposed mice and suggest that mitochondrial dysfunction plays an important role in the early stage of α-AMA induced liver failure.

Topics: Amanitins; Animals; Cell Line; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Energy Metabolism; Humans; Liver; Liver Failure; Metabolomics; Mice, Inbred BALB C; Mitochondria, Liver; Mushroom Poisoning; Time Factors

Topics: Acetylcysteine; Amanitins; Humans; Mushroom Poisoning

Topics: Acetylcysteine; Amanitins; Humans; Mushroom Poisoning

Topics: Amanita; Amanitins; Chromatography, High Pressure Liquid; Cooking; Forensic Toxicology; Hot Temperature; Humans; Mushroom Poisoning

To describe the clinical course, treatment, and outcome of 5 dogs following ingestion of toxic Amanita spp. mushrooms containing amatoxins using an adapted version of the Santa Cruz protocol developed for people.. Five dogs were presented with clinical signs compatible with amanitin toxicity with witnessed ingestion noted in 3 of 5 dogs. Clinical findings included acute onset vomiting and diarrhea, lethargy, and hepatopathy including signs of fulminant hepatic failure (increased liver enzyme activities, hyperbilirubinemia, prolonged clotting times, and hypoglycemia were noted among these cases). Urine toxicological screening confirmed the presence of Amanita toxins in 4 cases with expert mycologist speciation in the fifth. Core interventions included percutaneous biliary drainage, use of octreotide, and early nil per os orders. All dogs survived to discharge with this treatment strategy.. This case series describes the use of a modified version of the Santa Cruz protocol to address amatoxin-induced fulminant hepatic failure in dogs. The protocol was safe, well tolerated, and all patients made a full clinical recovery.

Topics: Amanita; Amanitins; Animals; Dog Diseases; Dogs; Humans; Liver Failure, Acute; Male; Mushroom Poisoning

Topics: Administration, Intravenous; Aged; Amanita; Amanitins; Antitoxins; Female; Humans; Male; Multiple Organ Failure; Mushroom Poisoning; Rifampin; Treatment Outcome

Phallotoxins, toxic cyclopeptides found in wild poisonous mushrooms, are predominant causes of fatal food poisoning. For the early and rapid diagnosis mushroom toxin poisoning, a highly sensitive and robust monoclonal antibody (mAb) against phallotoxins was produced for the first time. The half-maximum inhibition concentration (IC

Topics: Amanitins; Animals; Antibodies, Monoclonal; Gold; Humans; Limit of Detection; Metal Nanoparticles; Mice; Molecular Structure; Mushroom Poisoning; Reagent Strips; Sensitivity and Specificity

Amatoxin poisoning is the main cause of death from accidental ingestion of poisonous mushrooms and a mortality rate of 27.3% has been reported in Thailand. Symptoms of mushroom ingestion are often confused with food poisoning; thus, gastroenteritis is not recognised as the first phase of poisoning. Our study assessed the efficacy of N-acetylcysteine (NAC) as a treatment for amatoxin poisoning. We retrospectively analysed 74 medical records over 12 years. The majority (70/74) were treated successfully with NAC; death in the remaining 4 (5.4%) patients was attributed to late presentation in three and advanced alcoholic cirrhosis in one.

Topics: Acetylcysteine; Amanitins; Female; Gastroenteritis; Humans; Male; Mushroom Poisoning; Retrospective Studies; Thailand; Treatment Outcome

Topics: Amanita; Amanitins; Antioxidants; China; Female; Humans; Liver; Liver Failure, Acute; Male; Middle Aged; Mushroom Poisoning; Thrombocytopenia

Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of α-amanitin (α-AMA) or γ-AMA, and 100 ng/mL of β-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography-mass spectrometry (LC-MS) methods.

Topics: Amanitins; Animals; Dog Diseases; Dogs; Humans; Immunoassay; Molecular Structure; Mushroom Poisoning; Point-of-Care Testing; Sensitivity and Specificity

Amatoxins, most of which are hepatotoxic, can cause fatal intoxication. While mushrooms in the amatoxin-containing Galerina genus are rare, they can poison humans and animals worldwide. Few studies have profiled the toxicity of Galerina marginata. In addition, many studies indicate that macrofungi can have different characteristics in different regions. In this study, the quantities of toxins present in G. marginata from different provinces in Turkey were analysed using reversed-phase high-performance liquid chromatography with ultraviolet detection (RP-HPLC-UV) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). G. marginata samples were collected from three different regions of Turkey. The taxonomic categorization of mushrooms was based on their micro- and macroscopic characteristics. The presence of toxins α-amanitin (AA), β-amanitin (BA), γ-amanitin (GA), phalloidin (PHD) and phallacidin (PHC) quantities were measured using RP-HPLC-UV and then were confirmed using LC-ESI-MS/MS. BA levels were higher than AA levels in G. marginata mushrooms collected from all three regions. Moreover, the levels of GA were below the detection limit and no phallotoxins were detected. This is the first study to identify and test the toxicity of G. marginata collected from three different regions of Turkey using RP-HPLC-UV. This is also the first study to confirm the UV absorption of amatoxins in G. marginata using LC-ESI-MS/MS, which is a far more sensitive process. More studies evaluating the toxicity of G. marginata in other geographic regions of the world are needed.

Topics: Alpha-Amanitin; Amanitins; Mushroom Poisoning; Toxins, Biological; Turkey

Amatoxins are known to be one of the main causes of serious to fatal mushroom intoxication. Thorough treatment, analytical confirmation, or exclusion of amatoxin intake is crucial in the case of any suspected mushroom poisoning. Urine is often the preferred matrix due to its higher concentrations compared to other body fluids. If urine is not available, analysis of human blood plasma is a valuable alternative for assessing the severity of intoxications. The aim of this study was to develop and validate a liquid chromatography (LC)-high resolution tandem mass spectrometry (HRMS/MS) method for confirmation and quantitation of α- and β-amanitin in human plasma at subnanogram per milliliter levels. Plasma samples of humans after suspected intake of amatoxin-containing mushrooms should be analyzed and amounts of toxins compared with already published data as well as with matched urine samples. Sample preparation consisted of protein precipitation, aqueous liquid-liquid extraction, and solid-phase extraction. Full chromatographical separation of analytes was achieved using reversed-phase chromatography. Orbitrap-based MS allowed for sufficiently sensitive identification and quantification. Validation was successfully carried out, including analytical selectivity, carry-over, matrix effects, accuracy, precision, and dilution integrity. Limits of identification were 20 pg/mL and calibration ranged from 20 pg/mL to 2000 pg/mL. The method was applied to analyze nine human plasma samples that were submitted along with urine samples tested positive for amatoxins. α-Amanitin could be identified in each plasma sample at a range from 37-2890 pg/mL, and β-amanitin was found in seven plasma samples ranging from <20-7520 pg/mL. A LC-HRMS/MS method for the quantitation of amatoxins in human blood plasma at subnanogram per milliliter levels was developed, validated, and used for the analysis of plasma samples. The method provides a valuable alternative to urine analysis, allowing thorough patient treatment but also further study the toxicokinetics of amatoxins.

Topics: Amanitins; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Humans; Mushroom Poisoning; Tandem Mass Spectrometry

A 34-year-old woman from Thai origin developed acute liver failure after ingestion of a soup which contained the death cap (Amanita phalloides).. In patients with poisoning due to amatoxin-containing mushrooms, gastro-intestinal complaints usually develop several hours after ingestion, followed by acute hepatic failure which occasionally leads to death. The incidence of reported mushroom poisonings in the Netherlands has increased in 2019, which is possibly associated with migration of asylum seekers who regularly pick and eat mushrooms.. In the Netherlands mushroom intoxication is rare. Therefore, there is a lack of knowledge among health care personnel and foragers. The present case report highlights the importance of awareness of the poisonous death cap to prevent intoxications and optimize treatment decisions.

Topics: Adult; Amanita; Amanitins; Female; Humans; Liver Failure, Acute; Mushroom Poisoning; Netherlands

Topics: Adult; Amanita; Amanitins; Breast Feeding; Female; Humans; Infant, Newborn; Middle Aged; Milk, Human; Mushroom Poisoning; Treatment Outcome

Eating mushrooms known to contain amatoxin is fraught with serious complications. The analysis of the relevant literature publications revealed no article with the description of the histological picture of the internal organs in the subjects intoxicated with amatoxin. It is known, however, that such poisoning is associated with the severe irreversible injuries to all intracellular protein structures the character of which depends on time. Specifically, acute amatoxin intoxication produces the well apparent clinical picture within 6 days after intake of the poison. It is characterized by acute renal and hepatic insufficiency in the combination with the injury to the conducting system of heart and the myocrardium itself. Thereafter, the disseminated intravascular coagulation (DIC) syndrome developed accompanied by the signs of progressive tissue hypoxia that ended in death on day 9. The histological study has demonstrated necrotic foci in the liver and oedematous hepatic stroma. Kidneys underwent multiple hemorrhages, necrosis of convoluted tubules and well apparent hydropic protein dystrophy of their epithelium. The adrenal glands showed up signs of necrosis and hemorrhage. It is concluded that poisoning with mushrooms (amatoxin) should be regarded as the most probable cause of the condition requiring differential diagnostics between acute gastroenteritis and renal insufficiency.. Употребление в пищу грибов, содержащих аматоксин, опасно серьезными осложнениями. Анализ источников литературы не выявил ни одного сообщения, в котором бы приводилась гистологическая картина внутренних органов у лиц, отравившихся аматоксином. Известно, что при таких отравлениях необратимые изменения обусловлены повреждением всех клеточных белковых структур и имеют различную временнýю составляющую. В случае острого отравления аматоксином развернутую клиническую картину в виде острой почечной и печеночной недостаточности, а также поражения проводящей системы сердца и самого миокарда наблюдали на 6-е сутки. Смерть наступила на 9-е сутки на фоне массивного ДВС-синдрома и признаков прогрессирующей тканевой гипоксии. При гистологическом исследовании наблюдали очаги некроза и отек стромы печени, множественные кровоизлияния, некроз извитых канальцев почек, резко выраженную белковую гидропическую дистрофию эпителия извитых канальцев, некроз и кровоизлияния в ткани надпочечников. Отравление грибами (аматоксином) необходимо рассматривать в качестве наиболее вероятной причины при дифференциальной диагностике острого гастроэнтерита и почечной недостаточности.

Topics: Amanita; Amanitins; Humans; Kidney; Liver; Mushroom Poisoning

Mushroom poisoning with Amanita phalloides or similar species can lead to liver failure with 10-30% mortality rates. We aimed at defining the prognostic value of urinary amatoxin quantification in patients with hepatotoxic mushroom poisoning.. Data from 32 patients with hepatotoxic mushroom poisoning (Hospital Clínic Barcelona, 2002-16) in whom urinary amatoxins were determined (ELISA) were retrospectively reviewed. Correlations between urinary amatoxin and collected baseline variables with outcomes including hepatotoxicity (ALT>1000 U/L), severe acute liver injury (ALI, prothrombin <50%), acute liver failure (ALF, ALI and encephalopathy), transplantation/death and hospital length-of-stay, were evaluated.. 12/32 patients developed increased aminotransferase activity. Among the 13/32 amatoxin negative patients, 1 developed ALI and 12/13 no hepatotoxicity. Among the 19/32 amatoxin positive patients, 8/19 (42%) developed hepatotoxicity, including 5 who progressed to severe ALI, of whom 3 developed ALF (2 deaths, 1 transplantation). Urinary amatoxin and prothrombin were independent predictors of hepatotoxicity, ALT peak values (along with age) and hospital length-of-stay. In positive amatoxins patients, urinary concentrations > 55 ng/ml (or a baseline prothrombin ≤ 83%), were associated to hepatotoxicity (presented by 8/9 patients with ALT>1000 U/L). Among 5 patients with urinary amatoxin ≥ 70 ng/ml, 4 developed severe ALI.. In patients with hepatotoxic mushroom poisoning, a negative urinary amatoxin quantification within 72h of intake ruled out the risk of hepatotoxicity in 92% of patients, whereas positive urinary amatoxins were associated with hepatotoxicity and severe ALI. Concentrations >55 ng/ml and ≥ 70 ng/ml were predictive of hepatotoxicity and severe ALI, respectively.

Topics: Adolescent; Adult; Aged; Amanitins; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Liver Failure, Acute; Logistic Models; Male; Middle Aged; Mushroom Poisoning; Predictive Value of Tests; Retrospective Studies; Spain; Young Adult

The most frequently reported fatal Lepiota ingestions are due to L. brunneoincarnata. We present a case of L. brunneoincarnata poisoning with endoscopic nasobiliary drainage known to be the first in China. The patient suffered gastrointestinal symptoms 9 h post ingestion of mushrooms. The patient was hospitalized 4 days after eating the mushrooms with jaundice. The peak ALT, AST, APTT, TBIL and DBIL values of the patient were as follow: ALT, 2980 U/L (day 4 post ingestion); AST, 1910 U/L (day 4 post ingestion); APTT, 92.8 seconds (day 8 post ingestion), TBIL, 136 μmol/L (day 10 post ingestion), DBIL 74 μmol/L (day 10 post ingestion). UPLC-ESI-MS/MS was used to detect the peptide toxins in the mushroom and biological samples from the patient. We calculated that the patient may have ingested a total of 29.05 mg amatoxin from 300 g mushrooms, consisting of 19.91 mg α-amanitin, 9.1 mg β-amanitin, and 0.044 mg γ-amanitin. Amatoxins could be detected in bile even on day 6 after ingestion of L. brunneoincarnata. With rehydration, endoscopic nasobiliary drainage and intravenous infusion of Legalon SIL, the patient recovered after serious hepatotoxicity developed.

Topics: Agaricales; Amanitins; China; Drainage; Humans; Male; Middle Aged; Mushroom Poisoning; Silymarin

Topics: Amanitins; Critical Care; Humans; Liver; Mushroom Poisoning

Hyperbranched rolling circle amplification (HRCA) with a padlock probe (PLP) targeting the α-amanitin (α-AMA) gene, as a screening tool for the universal identification of lethal amanitas, was established in this study. With the isothermal HRCA assay, all of the lethal Amanita species tested from Phalloideae (10) were positive, while the non-Phalloideae Amanita species (15) and three amanitin-containing Lepiota and Galerina species were negative. Furthermore, the PLP based on α-AMA sequences from lethal Amanita species was effective for Amanita α-AMA, but not Amanita β-AMA or non-Amanita α-AMA. HRCA sensitivity was 100-fold higher than conventional PCR with a detection limit of 100 copies (recombinant plasmid containing α-AMA), and 0.2% lethal amanitas could be detected in dry mushroom blends. The HRCA method presented provided a rapid, specific, sensitive and low-cost identification tool for lethal amanitas.

Topics: Agaricales; Alpha-Amanitin; Amanita; Amanitins; Limit of Detection; Mushroom Poisoning; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Sensitivity and Specificity

In this study, the toxicology of A. exitialis, a lethal mushroom found in China, and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which they were assessed for signs of toxicity, as well as biochemical and pathological changes. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to assay the peptide toxins. The total peptide toxins in A. exitialis was 3482.6 ± 124.94 mg/kg. The beagles showed signs of toxicity, such as vomiting and diarrhea, at 12-48 h following ingestion of A. exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in plasma, as well as prothrombin time and activated partial thromboplastin time peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three dogs that were administered 60 mg/kg A. exitialis died at 24-72 h after ingesting the capsules. Additionally, liver histopathological examinations showed hemorrhagic necrosis of hepatocytes. α-Amanitin, β-amanitin, and phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis was ingested. A long latency period (12-24 h post A. exitialis ingestion) was observed in the dogs before the onset of gastrointestinal symptoms. There was acute liver damage thereafter. Gastric lavage and enhanced plasma clearance methods such as hemodialysis, hemoperfusion, or plasma exchange may be ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion. Enhanced excretion of amatoxins in urine could be effective within 2 days after ingestion of A. exitialis because amatoxins in 0-2 d urine accounted for more than 90% of the total urine excretion.

Topics: Alanine Transaminase; Amanita; Amanitins; Animals; Aspartate Aminotransferases; Dogs; Fungal Proteins; Liver Diseases; Male; Mushroom Poisoning; Partial Thromboplastin Time; Peptides, Cyclic; Prothrombin Time; Toxicokinetics

Acute liver failure (ALF) induced by amatoxin-containing mushrooms accounts for more than 90% of deaths in patients suffering from mushroom poisoning. However, due to the fact that most hospitals cannot identify the species of mushrooms involved, or detect amatoxins, the early diagnosis of amatoxin intoxication remains a significant challenge in clinical practice.. Two patients were had ingested wild mushrooms 15 hours before admission. Six hours prior to admission they experienced nausea, vomiting, weakness, abdominal pain and diarrhea. The species of mushrooms they had consumed could not be identified.. According to their delayed gastroenteritis, the two patients were clinically diagnosed with amatoxin poisoning. One week after the patients were discharged, the species of the mushrooms was identified as Amanita fuliginea and the diagnosis was confirmed.. The two patients were treated with silibinin, penicillin G and plasma exchange.. Although the two patients progressed to ALF they fully recovered and were discharged on day 10 after admission.. Our case reports suggested that patients with unidentified wild mushroom intoxication with delayed gastroenteritis could be clinically diagnosed with amatoxin poisoning; in such cases, liver coagulation function should be frequently evaluated. Early diagnosis and treatment are crucial for survival in patients with ALF induced by amatoxin poisoning.

Topics: Adult; Amanita; Amanitins; Anti-Bacterial Agents; Antioxidants; Diagnosis, Differential; Early Diagnosis; Female; Humans; Liver Failure, Acute; Middle Aged; Mushroom Poisoning; Penicillin G; Plasma Exchange; Silybin; Silymarin

Topics: Amanitins; Biomarkers; Chromatography, Liquid; Humans; Mushroom Poisoning; Nitrogen Isotopes; Tandem Mass Spectrometry

Rapid and accurate identification of multiple toxins for clinical diagnosis and treatment of mushroom poisoning cases is still a challenge, especially with the lack of authentic references. In this study, we developed an effective method for simultaneous identification of amanita peptide toxins by liquid chromatography coupled with photodiode array detection and ion trap time-of-flight mass spectrometry. The accuracy and selectivity of the methodology were validated through similar multiple fragmentation patterns and characteristic ions of standard α- and β-amanitin. The developed method could successfully separate and identify major toxic constituents in Amanita mushrooms. Two amatoxins and three phallotoxins were confirmed in a single run through their fragmentation patterns and characteristic ions, which can be used as diagnostic fragment ions to identify mushroom toxins in complex samples. Furthermore, the performance of the developed method was verified by using real biological samples, including plasma and urine samples collected from rats after intraperitoneal administration of toxins. Thus, the development methodology could be crucial for the accurate detection of mushroom toxins without standard references.

Topics: Amanita; Amanitins; Animals; Chromatography, High Pressure Liquid; Injections, Intraperitoneal; Mass Spectrometry; Mushroom Poisoning; Mycotoxins; Rats; Reference Standards; Reproducibility of Results

Cases of mushroom poisoning in Thailand have increased annually. During 2008 to 2014, the cases reported to the National Institute of Health included 57 deaths; at least 15 died after ingestion of amanitas, the most common lethal wild mushrooms inhabited. Hence, the aims of this study were to identify mushroom samples from nine clinically reported cases during the 7-year study period based on nuclear ITS sequence data and diagnose lethal peptide toxins using a reversed phase LC-MS method. Nucleotide similarity was identified using BLAST search of the NCBI database and the Barcode of Life Database (BOLD). Clade characterization was performed by maximum likelihood and Bayesian phylogenetic approaches. Based on BLAST and BOLD reference databases our results yielded high nucleotide similarities of poisonous mushroom samples to A. exitialis and A. fuliginea. Detailed phylogenetic analyses showed that all mushroom samples fall into their current classification. Detection of the peptide toxins revealed the presence of amatoxins and phallotoxins in A. exitialis and A. fuliginea. In addition, toxic α-amanitin was identified in a new provisional species, Amanita sp.1, with the highest toxin quantity. Molecular identification confirmed that the mushrooms ingested by the patients were members of the lethal amanitas in the sections Amanita and Phalloideae. In Thailand, the presence of A. exitialis was reported here for the first time and all three poisonous mushroom species provided new and informative data for clinical studies.

Topics: Amanita; Amanitins; Chromatography, Liquid; Databases, Genetic; Humans; Mass Spectrometry; Mushroom Poisoning; Retrospective Studies; Sequence Analysis, DNA; Thailand

Published estimates of survival associated with mushroom (amatoxin)-induced acute liver failure (ALF) and injury (ALI) with and without liver transplant (LT) are highly variable. We aimed to determine the 21-day survival associated with amatoxin-induced ALI (A-ALI) and ALF (A-ALF) and review use of targeted therapies.. Cohort study of all A-ALI/A-ALF patients enrolled in the US ALFSG registry between 01/1998 and 12/2014.. Of the 2224 subjects in the registry, 18 (0.8%) had A-ALF (n = 13) or A-ALI (n = 5). At admission, ALF patients had higher lactate levels (5.2 vs. 2.2 mm, P = 0.06) compared to ALI patients, but INR (2.8 vs. 2.2), bilirubin (87 vs. 26 μm) and MELD scores (28 vs. 24) were similar (P > 0.2 for all). Of the 13 patients with ALF, six survived without LT (46%), five survived with LT (39%) and two died without LT (15%). Of the five patients with ALI, four (80%) recovered and one (20%) survived post-LT. Comparing those who died/received LT (non-spontaneous survivors [NSS]) with spontaneous survivors (SS), N-acetylcysteine was used in nearly all patients (NSS 88% vs. SS 80%); whereas, silibinin (25% vs. 50%), penicillin (50% vs. 25%) and nasobiliary drainage (0 vs. 10%) were used less frequently (P > 0.15 for all therapies).. Patients with mushroom poisoning with ALI have favourable survival, while around half of those presenting with ALF may eventually require LT. Further study is needed to define optimal management (including the use of targeted therapies) to improve survival, particularly in the absence of LT.

Topics: Acetylcysteine; Adult; Amanitins; Chemical and Drug Induced Liver Injury; Cohort Studies; Female; Humans; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Mushroom Poisoning; North America; Penicillins; Registries; Silybin; Silymarin

Mushroom poisoning is a cause of major mortality and morbidity all over the world. Although Hong Kong people consume a lot of mushrooms, there are only a few clinical studies and reviews of local mushroom poisoning. This study aimed to review the clinical characteristics, source, and outcome of mushroom poisoning incidences in Hong Kong.. This descriptive case series review was conducted by the Hong Kong Poison Information Centre and involved all cases of mushroom poisoning reported to the Centre from 1 July 2005 to 30 June 2015.. Overall, 67 cases of mushroom poisoning were reported. Of these, 60 (90%) cases presented with gastrointestinal symptoms of vomiting, diarrhoea, and abdominal pain. Gastrointestinal symptoms were early onset (<6 hours post-ingestion) and not severe in 53 patients and all recovered after symptomatic treatment and a short duration of hospital care. Gastrointestinal symptoms, however, were of late onset (≥6 hours post-ingestion) in seven patients; these were life-threatening cases of amatoxin poisoning. In all cases, the poisonous mushroom had been picked from the wild. Three cases were imported from other countries, and four collected and consumed the amatoxin-containing mushrooms in Hong Kong. Of the seven cases of amatoxin poisoning, six were critically ill, of whom one died and two required liver transplantation. There was one confirmed case of hallucinogenic mushroom poisoning caused by Tylopilus nigerrimus after consumption of a commercial mushroom product. A number of poisoning incidences involved the consumption of wild-harvested dried porcini purchased in the market.. Most cases of mushroom poisoning in Hong Kong presented with gastrointestinal symptoms and followed a benign course. Life-threatening cases of amatoxin poisoning are occasionally seen. Doctors should consider this diagnosis in patients who present with gastrointestinal symptoms that begin 6 hours or more after mushroom consumption.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Aged, 80 and over; Amanitins; Child; Child, Preschool; Diarrhea; Female; Gastrointestinal Diseases; Hong Kong; Humans; Male; Middle Aged; Mushroom Poisoning; Retrospective Studies; Vomiting; Young Adult

BACKGROUND Fractionated plasma separation and absorption (FPSA) is an extracorporeal liver support method that detoxifies accumulated toxins. There are limited data of its use in the treatment of Amanita phalloides intoxication. The objective of this study was to investigate whether FPSA before liver transplantation improves patients' short-term post liver transplantation survival in Amanita phalloides poisoning. MATERIAL AND METHODS The study population consisted of ten patients who had liver transplantation (LT) due to acute liver failure (ALF) caused by Amanita phalloides poisoning. Six patients were treated with FPSA before liver transplantation. All the patients who were started on FPSA were also placed on the liver transplantation list according to emergent liver transplantation criteria. RESULTS Patients treated with FPSA were in a more severe clinical condition presenting in higher mean MELD, total bilirubin, INR and ammonia along with more frequent hypoglycemia and hepatic encephalopathy grade 3/4. FPSA group had longer mean waiting time on the recipient list (3.5 vs. 1.25 days) but inferior thirty-day survival rate (16.5% vs. 100%). CONCLUSIONS When conservative medical modalities are ineffective, the only treatment for Amanita phalloides poisoning is a liver transplant. Although FPSA treated patients had inferior post-LT survival, FPSA was found to prolong the pre surgical waiting time for critically ill patients, consequently giving a chance of life-saving procedure.

Topics: Adult; Aged; Amanita; Amanitins; Female; Humans; Kaplan-Meier Estimate; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Mushroom Poisoning; Retrospective Studies; Sorption Detoxification; Time Factors; Waiting Lists; Young Adult

Lethal amanitas (Amanita sect. Phalloideae) are responsible for 90% of all fatal mushroom poisonings. Since 2000, more than ten new lethal Amanita species have been discovered and some of them had caused severe mushroom poisonings in China. However, the contents and distribution of cyclopeptides in these lethal mushrooms remain poorly known. In this study, the diversity of major cyclopeptide toxins in seven Amanita species from Eastern Asia and three species from Europe and North America were systematically analyzed, and a new approach to inferring phylogenetic relationships using cyclopeptide profile was evaluated for the first time. The results showed that there were diversities of the cyclopeptides among lethal Amanita species, and cyclopeptides from Amanita rimosa and Amanita fuligineoides were reported for the first time. The amounts of amatoxins in East Asian Amanita species were significantly higher than those in European and North American species. The analysis of distribution of amatoxins and phallotoxins in various Amanita species demonstrated that the content of phallotoxins was higher than that of amatoxins in Amanita phalloides and Amanita virosa. In contrast, the content of phallotoxins was significantly lower than that of amatoxins in all East Asian lethal Amanita species tested. However, the distribution of amatoxins and phallotoxins in different tissues showed the same tendency. Eight cyclopeptides and three unknown compounds were identified using cyclopeptide standards and high-resolution MS. Based on the cyclopeptide profiles, phylogenetic relationships of lethal amanitas were inferred through a dendrogram generated by UPGMA method. The results showed high similarity to the phylogeny established previously based on the multi-locus DNA sequences.

Topics: Amanita; Amanitins; Chromatography, High Pressure Liquid; Mass Spectrometry; Mushroom Poisoning; Peptides, Cyclic; Phylogeny; Reference Standards

Most of the fatal cases of mushroom poisoning are caused by Amanita phalloides. The amount of toxin in mushroom varies according to climate and environmental conditions. The aim of this study is to measure α-, β-, and γ-amanitin with phalloidin and phallacidin toxin concentrations. Six pieces of A. phalloides mushrooms were gathered from a wooded area of Düzce, Turkey, on November 23, 2011. The mushrooms were broken into pieces as spores, mycelium, pileus, gills, stipe, and volva. α-, β-, and γ-Amanitin with phalloidin and phallacidin were analyzed using reversed-phase high-performance liquid chromatography. As a mobile phase, 50 mM ammonium acetate + acetonitrile (90 + 10, v/v) was used with a flow rate of 1 mL/min. C18 reverse phase column (150 × 4.6 mm; 5 µm particle) was used. The least amount of γ-amanitin toxins was found at the mycelium. The other toxins found to be in the least amount turned out to be the ones at the spores. The maximum amounts of amatoxins and phallotoxin were found at gills and pileus, respectively. In this study, the amount of toxin in the spores of A. phalloides was published for the first time, and this study is pioneering to deal with the amount of toxin in mushrooms grown in Turkey.

Topics: Alpha-Amanitin; Amanita; Amanitins; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Forests; Fruiting Bodies, Fungal; Humans; Mushroom Poisoning; Mycelium; Peptides, Cyclic; Phalloidine; Species Specificity; Spectrophotometry, Ultraviolet; Spores, Fungal; Turkey

Amatoxin poisoning from the genus Lepiota may have a deadly outcome, although this is not seen as often as it is from the genus Amanita. In this report, we present a patient who was poisoned by a sublethal dose of Lepiota brunneoincarnata mushrooms. The patient was hospitalized 12 hours after eating the mushrooms. The patient's transaminase levels increased dramatically starting on day 4. Aspartate transaminase peaked at 78 hours. Starting at 1265 IU/L, alanine transaminase peaked at 90 hours at 5124 IU/L. The patient was discharged on day 8 to outpatient care, and his transaminase levels returned to normal ranges in the subsequent days. A toxin analysis was carried out on the mushrooms that the patient claimed to have eaten. Using reversed-phase high-performance liquid chromatography analysis, an uptake of approximately 19.9 mg of amatoxin from nearly 30 g of mushrooms was calculated. This consisted of 10.59 mg of α-amanitin, 9.18 mg of β-amanitin, and 0.16 mg of γ-amanitin. In conclusion, we present a patient from Turkey who was poisoned by L. brunneoincarnata mushrooms.

Topics: Adult; Agaricales; Alanine Transaminase; Alpha-Amanitin; Amanitins; Aspartate Aminotransferases; Chromatography, High Pressure Liquid; Humans; Liver; Male; Mushroom Poisoning; Turkey

Serious to fatal toxicity may occur with amanitin-containing mushrooms ingestions. A Lepiota brunneoincarnata familial poisoning with hepatic toxicity is reported. In such poisonings, acute gastroenteritis may be firstly misdiagnosed leading to delay in preventing liver dysfunction by silibinin or penicillin G. Mushroom picking finally requires experience and caution.

Topics: Administration, Oral; Adult; Agaricales; Amanitins; Antidotes; Charcoal; Child; Diagnosis, Differential; Emergency Service, Hospital; Female; Fluid Therapy; Follow-Up Studies; Humans; Male; Mushroom Poisoning

This paper presents a method for the simultaneous determination of α-amanitin, β-amanitin and muscarine in human urine by solid-phase extraction (SPE) and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry. The method can be used for a diagnostics of mushroom poisonings. Different SPE cartridges were tested for sample preparation, namely hydrophilic modified reversed-phase (Oasis HLB) and polymeric weak cation phase (Strata X-CW). The latter gave better results and therefore it was chosen for the subsequent method optimization and partial validation. In the course of validation, limits of detection, linearity, intraday and interday precisions and recoveries were evaluated. The obtained LOD values of α-amanitin and β-amanitin were 1ng/mL and of muscarine 0.09ng/mL. The intraday and interday precisions of human urine spiked with α-amanitin (10ng/mL), β-amanitin (10ng/mL) and muscarine (1ng/mL) ranged from 6% to 10% and from 7% to 13%, respectively. The developed method was proved to be a relevant tool for the simultaneous determination of the studied mushroom toxins in human urine after mushroom poisoning.

Topics: Adolescent; Aged, 80 and over; Amanitins; Chromatography, Liquid; Female; Forensic Toxicology; Humans; Limit of Detection; Male; Mass Spectrometry; Muscarine; Mushroom Poisoning; Solid Phase Extraction

Mushroom poisonings occur when ingestion of wild mushrooms containing toxins takes place, placing the consumers at life-threatening risk. In the present case report, an unusual multiple poisoning with isoxazoles- and amatoxins-containing mushrooms in a context of altered mental state and poorly controlled hypertension is presented. A 68-year-old female was presented to São João hospital (Portugal) with complaints of extreme dizziness, hallucinations, vertigo and imbalance, 3 h after consuming a stew of wild mushrooms. The first observations revealed altered mental state and elevated blood pressure. The examination of cooked mushroom fragments allowed a preliminary identification of Amanita pantherina. Gas chromatography-mass spectrometry (GC-MS) showed the presence of muscimol in urine. Moreover, through high-performance liquid chromatography-ultraviolet detection (HPLC-UV) analysis of the gastric juice, the presence of α-amanitin was found, showing that amatoxins-containing mushrooms were also included in the stew. After 4 days of supportive treatment, activated charcoal, silybin and N-acetylcysteine, the patient recovered being discharged 10 days post-ingestion with no organ complications. The prompt and appropriate therapy protocol for life-threatening amatoxins toxicity probably saved the patient's life as oral absorption was decreased and also supportive care was immediately started.

Topics: Acetylcysteine; Agaricales; Aged; Alpha-Amanitin; Amanita; Amanitins; Charcoal; Female; Gas Chromatography-Mass Spectrometry; Humans; Isoxazoles; Mushroom Poisoning; Silybin; Silymarin

There are few data estimating the human lethal dose of amatoxins or of the toxin level present in ingested raw poisonous mushrooms. Here, we present a patient who intentionally ingested several wild collected mushrooms to assess whether they were poisonous. Nearly 1 day after ingestion, during which the patient had nausea and vomiting, he presented at the emergency department. His transaminase levels started to increase starting from hour 48 and peaking at hour 72 (alanine aminotransferase 2496 IU/L; aspartate aminotransferase 1777 IU/L). A toxin analysis was carried out on the mushrooms that the patient said he had ingested. With reversed-phase high-performance liquid chromatography analysis, an uptake of approximately 21.3 mg amatoxin from nearly 50 g mushroom was calculated; it consisted of 11.9 mg alpha amanitin, 8.4 mg beta amanitin, and 1 mg gamma amanitin. In the urine sample taken on day 4, 2.7 ng/mL alpha amanitin and 1.25 ng/mL beta amanitin were found, and there was no gamma amanitin. Our findings suggest that the patient ingested approximately 0.32 mg/kg amatoxin, and fortunately recovered after serious hepatotoxicity developed.

Topics: Amanita; Amanitins; Chromatography, High Pressure Liquid; Humans; Male; Middle Aged; Mushroom Poisoning

Poisoning from Amanita group of mushrooms comprises approximately 3% of all poisonings in our country and their being responsible for nearly the entire fatal mushroom poisonings makes them important. These mushrooms contain primarily two types of toxins, amatoxins and phallotoxins. Phallotoxins have a more limited toxicity potential and they primarily consist of phalloidin (PHN) and phallacidin (PCN). Amatoxins, on the other hand, are very toxic and they primarily consist of alpha-amanitin (AA), beta-amanitin (BA) and gamma-amanitin (GA). Toxin levels can vary among various species, even among varieties of the same species, of Amanita mushroom family. Revealing the differences between the toxin compositions of the Amanita species that grow in our region may contribute to the clinics of poisonings. Our study aims at showing in detail the toxin levels in various parts of Amanita verna mushroom. A. verna mushrooms needed for toxin analysis were collected from Kozak Plateau near Ayvalik county of Balıkesir, Turkey in April 2013. The mushrooms were divided into their parts as pileus, gills, stripe and volva. Following the procedures required before the analysis, the AA, BA, GA, PHN and PCN levels were measured using the RP-HPLC method. While the lowest level of amatoxin was in the volva of the mushroom, the highest was measured in the gills. This was followed by pileus and stripe where the levels were close to each other. Similarly, the highest level of phallotoxin was measured in the gills. Gamma toxin and phalloidin were at lower amounts than the other toxins. A. verna is frequently confused with edible mushrooms with white caps due to its macroscopic similarity. If just one of them is eaten by mistake by an adult person with no mushroom experience, it can easily poison them. The amount of amatoxin is more as compared to Amanita phalloides and A. phalloides var. alba. Particularly, the AA and BA levels are approximately three times higher, whereas GA levels are lower. Similarly, the level of PCN is approximately four times higher as compared to A. phalloides and A. phalloides var. alba; by contrast, the level of PNH is about a half of theirs. In summary, it can be said that A. verna is a more toxic mushroom than A. phalloides and has a higher rate of mortality. With our study, the amatoxin and phallotoxin concentrations and distribution in A. verna mushrooms were shown in detail for the first time and it would be useful to carry out more similar studies with

Topics: Amanita; Amanitins; Chromatography, High Pressure Liquid; Humans; Mushroom Poisoning; Species Specificity; Turkey

Alpha- and beta-amanitins are the main toxins of the poisonous Amanita phalloides mushroom. Although there are many studies available concerning alpha-amanitin, there are limited data about beta-amanitin in the literature. Therefore, this study is aimed at comparing the toxic effects of alpha- and beta-amanitin on the MCF-7 cell line.. The alpha- and beta-amanitins used for this research were purified from Amanita phalloides by preparative high-performance liquid chromatography. The MCF-7 breast cancer cell line was used, and specific concentrations of the toxins (100, 10, 1, 0.1, and 0.01 μg/mL) were applied to the cells. The MTT test was performed to determine the level of toxicity, and the quantity of protein in the cell was measured using the biuret test.. The aLpha-amanitin showed a higher toxicity at 36 h, while the highest inhibition of protein synthesis by the beta-amanitin was observed at 24 h.. It was shown that the beta-amanitin may be responsible for toxicity, like alpha-amanitin, in Amanita phalloides mushroom poisoning. The early inhibition of protein synthesis for beta-amanitin might be useful for future experiments and research.

Topics: Alpha-Amanitin; Amanitins; Humans; MCF-7 Cells; Mushroom Poisoning

Topics: Amanita; Amanitins; Fatal Outcome; Female; Humans; Middle Aged; Mushroom Poisoning

Topics: Amanitins; Humans; Liver Failure, Acute; Liver Transplantation; Male; Mushroom Poisoning

Accidental or deliberate poisoning of food is of great national and international concern. Detecting and identifying potentially toxic agents in food is challenging due to their large chemical diversity and the complexity range of food matrices. A methodology is presented whereby toxic agents are identified and further characterized using a two-step approach. First, generic screening is performed by LC/MS/MS to detect toxins based on a list of selected potential chemical threat agents (CTAs). After identifying the CTAs, a second LC/MS analysis is performed applying accurate mass determination and the generation of an attribution profile. To demonstrate the potential of the methodology, toxins from the mushrooms Amanita phalloides and Amanita virosa were analyzed. These mushrooms are known to produce cyclic peptide toxins, which can be grouped into amatoxins, phallotoxins and virotoxins, where α-amanitin and β-amanitin are regarded as the most potent. To represent a typical complex food sample, mushroom stews containing either A. phalloides or A. virosa were prepared. By combining the screening method with accurate mass analysis, the attribution profile for the identified toxins and related components in each stew was established and used to identify the mushroom species in question. In addition, the analytical data was consistent with the fact that the A. virosa specimens used in this study were of European origin. This adds an important piece of information that enables geographic attribution and strengthens the attribution profile.

Topics: Amanita; Amanitins; Chromatography, Liquid; Humans; Mass Spectrometry; Mushroom Poisoning; Peptides, Cyclic; Phalloidine; Poisons

Picking wild mushrooms is a popular pastime in Switzerland. Correct identification of the species is difficult for laypersons. Ingestion of toxic mushrooms may result in serious toxicity, including death. The aim of the study is to analyze and describe the circumstances of exposure to mushrooms, and to define the clinical relevance of mushroom poisoning for humans in Central Europe.. We performed a retrospective case study and analyzed all inquiries concerning human exposures to mushrooms (n = 5638, 1.2% of all inquiries) which were reported to the Swiss Toxicological Information Centre between January 1995 and December 2009.. The most frequent reason for contacting the poison center in cases of adult exposure was toxicity resulting from edible species. Pediatric exposure predominantly occurred from mushrooms found around the home. Severe symptoms have not only been observed after ingestion of non-amatoxin-containing toxic mushrooms, i.e. Boletus sp. and Cortinarius sp., but also after meals of edible species. The mortality of confirmed amatoxin poisonings was high (5/32) compared to other reports.. Inquiries regarding mushroom poisoning were a relatively infrequent reason for contacting the poison center. Nevertheless, accidental ingestion of toxic mushrooms can be responsible for severe or fatal poisonings. Although pediatric exposure to mushrooms found around the home has not led to serious toxicity in this study, prevention of exposure is warranted. Inspection of wild mushrooms by a certified mushroom expert or a mycologist seems to be a safe procedure which should be recommended.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amanitins; Child; Child, Preschool; Eating; Female; Humans; Infant; Male; Middle Aged; Mushroom Poisoning; Poison Control Centers; Seasons; Switzerland; Young Adult

To investigate the effectiveness and safety of extracorporeal detoxification using the fractionated plasma separation and adsorption system (FPSA, Prometheus® 4008H, Fresenius Medical Care, Germany) in patients suffering from acute liver failure due to intoxication with Amanita phalloides (AP) toxin.. The study population consisted of 20 patients with proven AP intoxication (FPSA treatment group n=9, control group n=11). Urinary amanitin toxin concentration was measured by the Amanitin ELISA Kit (Bühlmann Laboratories, Germany, cut off level 1.5 ng/ml). All patients received standard medical treatment with activated charcoal, i.v. crystalloid fluids, silibinine and N-acetylcysteine. Additionally 9 patients underwent treatment with FPSA until undetectable amanitin levels.. Mean urinary amanitin levels were significantly reduced by FPSA with 42.5 +/- 21.9 ng/ml before and 1.2 +/- 0.31 ng/ml after treatment (p=0.04). No hemodynamic, respiratory or hematological complications were observed. None of the patients had to undergo liver transplantation. All patients in the treatment group survived and were discharged fully recovered. One patient in the control group died due to shock and lactic acidosis; one patient remained dialysis dependent. Mean duration of hospital stay was 7.1 days in the treatment group and 11.7 days in the control group (p=0.30).. Use of liver support therapy by fractionated plasma separation and adsorption (Prometheus®) offers a safe way for elimination of Amanita toxin with the potential to avoid the need for liver transplantation.

Topics: Adult; Aged; Amanita; Amanitins; Bilirubin; Blood Coagulation; Extracorporeal Circulation; Female; Humans; Liver Failure, Acute; Male; Middle Aged; Mushroom Poisoning; Sorption Detoxification; Treatment Outcome

OBJECTIVE. We aimed to determine clinical and laboratory findings that were different between those patients who died and those who survived and to look for factors associated with the mortality in amatoxin-containing mushroom poisoning. METHODS. The mushroom poisoning patients who were admitted to our clinic between 1996 and 2009 were retrospectively evaluated. The diagnosis was based on a history of mushroom ingestion, clinical picture and the presence of serum alpha-amanitin. Patients were divided into two groups as the survival group and the fatality group. Clinical and laboratory findings were compared between the two groups. Relation between variables and clinical outcome was analyzed. RESULTS. A total of 144 amatoxin poisoning patients were included in this study. Patients who died were more likely to have demonstrated low mean arterial pressure, encephalopathy, mucosal hemorrhage, oliguria-anuria, hypoglycemia, and thrombocytopenia during the hospitalization. Low sodium values and high urea, AST, ALT, total bilirubin, LDH, prothrombin time, international normalized ratio, and activated partial thromboplastin time values were associated with increased likelihood of mortality. Nineteen patients developed acute renal failure. Fourteen patients developed acute hepatic failure. All the 14 patients who died developed acute hepatic failure. The mortality rate was 9.7%. CONCLUSIONS. The factors associated with mortality determined in this retrospective study may be helpful for clinical outcome assessment and monitoring of patients with amatoxin-containing mushroom poisoning.

Topics: Adult; Amanitins; Female; Hemoperfusion; Humans; Liver Failure, Acute; Male; Middle Aged; Mushroom Poisoning; Retrospective Studies

Topics: Amanita; Amanitins; Electroencephalography; Follow-Up Studies; Humans; Infant; Liver Failure, Acute; Liver Transplantation; Male; Mushroom Poisoning; Treatment Outcome

Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.

Topics: Acetylcysteine; Algorithms; Amanitins; Anti-Bacterial Agents; Antioxidants; Ceftazidime; Databases, Factual; Decision Making; Decision Theory; Factor Analysis, Statistical; Humans; Multivariate Analysis; Mushroom Poisoning; Retrospective Studies; Silybin; Silymarin; Survival; Survival Rate

There are some serious poisonings with toxic mushroom species in Poland every year. Good prognostics in the cases is correlated to short time from mushroom consumption to hospitalization, correct distinguish not specific gastrointestinal and Amanita phalloides syndrome and immediately specific treatment. The purpose of the paper was to make appraisal of usefulness of amanitin blood and urine determination and transaminases activity determination (ALT, AST) in diagnostics of mushroom poisoned patients up to three days after mushroom consumption. The material was twenty two retrospective histories of mushroom poisoned patients treated in the years 2007-2008. Amanitin blood and urine determinations were made by ELISA method. Urine amanitin results in samples collected within 40 h from mushroom consuming were positive in all Amanita phalloides syndrome cases. Serum amanitin determination was not useful for the diagnostics. Trans-aminases activity determinations let to distinguish Amanita phalloides syndrome on the second and the third day after mushroom consumption. In the first poisoning phase (within 24 h), the ALT and AST activities were in normal ranges and only amanitin urine determination let to confirm or exclude Amanita phalloides poisoning. Amanitin urine determinations were useful to take fast decision about specific treatment and avoid internal organs dysfunctions.

Topics: Amanitins; Female; Humans; Male; Mushroom Poisoning; Poland

There is a paucity of knowledge about prenatal and perinatal risks through maternal amatoxin poisoning. No symptoms of amatoxin intoxication, except for a slight temporary increase in liver enzymes activity, occurred in a term newborn after delivery despite an Amanita phalloides intoxication of the mother 2 days before. Considering previous reports, severe fetal intoxication may not occur during the entire pregnancy.

Topics: Adult; Amanitins; Female; Humans; Infant, Newborn; Liver Function Tests; Male; Mushroom Poisoning; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk Factors

Topics: Alpha-Amanitin; Amanitins; Animals; Antidotes; Chemical and Drug Induced Liver Injury; Cimetidine; Humans; Mice; Mushroom Poisoning

Current treatment of amatoxin poisoning includes the administration of silibinin and penicillin in combination or silibinin alone. The aim of this study was to compare both therapeutic regimes.. Of 604 patients with the suspected diagnosis of amatoxin poisoning 367 were retrospectively analysed: 118 patients had received silibinin alone and 249 patients silibinin in combination with penicillin. Logistic regression analyses were applied to investigate the efficacy of both therapeutic regimens by comparing death and liver transplantation rates. A potentially independent effect on outcome of age, sex, year of treatment, latency period of symptoms and start of silibinin therapy was taken into account.. In the group who had received the combination of silibinin and penicillin 8.8% died or underwent liver transplantation compared to 5.1% in the group of those who had received silibinin alone. The risk of death or organ transplantation was thus reduced by nearly 40% in the latter group (adjusted odds ratio: 0.58; 95% CI: 0.21-1.57; p=0.28). A longer latency period (< or =12h vs. >12h) was associated with a significant reduction of this risk (adjusted OR.: 6.10; 95% CI:1.77-21.3; p=0.004). A later start of silibinin therapy (>24h vs. < or = 24h) was associated with a tendency toward an increased frequency of death or organ transplantation (adjusted OR.: 3.0; 95% CI: 0.96-9.20; p=0.059).. A lower death and transplantation rate was observed in the silibinin treatment group than in group treated with silibinin combined with penicillin. However, this difference was not statistically significant. The high risk ratio relating to the time-dependent effect of silibinin suggests its efficaciousness in the treatment of amatoxin poisoning. The latency period was assessed as an independent prognostic factor.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amanita; Amanitins; Antidotes; Antioxidants; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Liver Transplantation; Logistic Models; Male; Middle Aged; Mushroom Poisoning; Penicillins; Prognosis; Retrospective Studies; Severity of Illness Index; Silybin; Silymarin; Time Factors

The identification of toxic oligopeptides employing CE-ESI-MS is presented. The analytes studied ama- and phallotoxins are of significant forensic interest because over 90% of the lethal cases of fungus poisoning in man are caused by species of Amanita which contain these toxins. A CE method was developed to separate the toxins alpha-, beta- and gamma-amanitin, phalloidin and phallacidin. Their fragmentation patterns in MS(n) experiments were investigated in the positive and in the negative ion mode, also the influence of the sheath liquid mixture of the used interface on the S/N. Method validation included the determination of the LOD and the repeatability of the migration time and peak area for both detection modes. With the optimized method LODs of 13-79 ng/mL (17-87 nmol/L) were reached. The CE-MS procedure was successfully applied to the identification of ama- and phallotoxins in extracts of air-dried mushroom samples.

Topics: Amanita; Amanitins; Electrophoresis, Capillary; Humans; Molecular Structure; Mushroom Poisoning; Mycotoxins; Oligopeptides; Peptides, Cyclic; Phalloidine; Spectrometry, Mass, Electrospray Ionization

Amanitins are toxins found in species of the mushroom genera Amanita, Lepiota and Galerina. Intoxication after ingestion of these mushrooms can be fatal with an estimated 20% of mortality rate. An early diagnosis is necessary in order to avoid invasive and expensive therapy and to improve patient's prognosis. In this paper, a Capillary Zone Electrophoresis method was developed and validated to determine alpha- and beta-amanitin in urine in less than 7 min using 5 mM, pH 10 borate buffer as background electrolyte. The separation conditions were: capillary: 75 microm I.D., 41 cm effective length, 48 cm total length, 25 degrees C, 20 KV and PDA detection at 214 nm. Sample treatment for analysis only required urine dilution in background electrolyte. The method was validated following established criteria and was found to be selective, linear in the range 5-100 ng/ml. Intra- and inter-day precision and accuracy were within required limits. Limit of detection (LOD) and limit of quantification (LOQ) were 1.5 and 5 ng/ml, respectively. Eight urine samples from suspected cases of intoxication with amanitins were analyzed after 2 years of storage at -20 degrees C, and beta-amanitin was determined in two samples with concentrations of 53 and 65 ng/ml, respectively. The method here described includes the use of non-aggressive reagents to the capillary or the system and is the first Capillary Electrophoresis method used to determine amanitins in clinical samples.

Topics: Alpha-Amanitin; Amanita; Amanitins; Borates; Buffers; Calibration; Chemistry, Clinical; Drug Stability; Electrophoresis, Capillary; Freezing; Humans; Hydrogen-Ion Concentration; Methanol; Molecular Structure; Mushroom Poisoning; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Time Factors

Poisoning with amanitin-containing hepatotoxic mushrooms demands extensive efforts from clinicians, toxicologists, and pathologists. Presumptive diagnoses are established by positive identification of the suspect mushroom along with the occurrence of consistent clinical signs. If the animal dies, hepatic lesions may suggest exposure to amanitin-containing mushrooms; however, lesions are nonspecific. A 15-week-old female Dachshund was presented to the referring veterinarian for acute onset of lethargy that quickly progressed to sternal recumbency. Despite supportive care, the dog remained lethargic and died approximately 12 hours after initial presentation. A pale tan liver was noted at necropsy. Microscopically, the liver showed panlobular coagulative necrosis of hepatocytes. A presumptive diagnosis of amanitin poisoning was based on suspect history of exposure to mushrooms, clinical signs, and pathologic findings. Exposure to amanitin was confirmed through detection of alpha-amanitin in the liver by liquid chromatography/mass spectrometry. The objective of this case report is to illustrate the essential components to a successful diagnostic work-up of a suspect case of hepatotoxic mushroom poisoning. Although hepatotoxic mushroom poisoning has been documented in dogs before, confirmatory techniques for biologic specimens have not been used previously in diagnostic investigations.

Topics: Amanita; Amanitins; Animals; Chromatography, Liquid; Dog Diseases; Dogs; Fatal Outcome; Female; Immunohistochemistry; Liver Diseases; Mass Spectrometry; Mushroom Poisoning

Two patients, a 54-year-old man and a 51-year-old woman, presented with abdominal pain, vomiting and diarrhoea; these symptoms developed 9 and 15 hours, respectively, after consumption of soup from mushrooms that they had picked themselves. As a result of these events, a third patient, a 55-year-old woman with diarrhoea who had also eaten the soup, also presented herself. The first patient recognised deathcap or death angel mushrooms (Amanita phalloides) on a photograph. All three patients were treated for amatoxin poisoning with a combination of high-dose penicillin G, silibinin and acetylcysteine intravenously. The poisoning was later confirmed by the results of urinalysis. The patients were discharged in good condition 8 days later.

Topics: Acetylcysteine; Amanita; Amanitins; Antioxidants; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mushroom Poisoning; Penicillin G; Silybin; Silymarin; Treatment Outcome; Urinalysis

The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority of severe mushroom poisonings by binding to RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no effective antidote for severe amatoxin poisoning. We compare the effectiveness of 5 potential antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled, murine model of amatoxin-induced hepatotoxicity.. One hundred eighty male Institute of Cancer Research mice were randomized into 6 equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6 mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9% normal saline solution. Four hours postinjection, each group of 30 mice was randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurements (alanine transaminase and aspartate transaminase), and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to the treatment group and divided into 5 categories according to percentage of hepatonecrosis.. Amanitin significantly increased aspartate transaminase in treated mice compared with normal saline solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03). None of the antidotal therapies were found to significantly decrease the increase in aminotransferases compared with controls. Further, none of the antidotal therapies demonstrated an important decrease in hepatonecrosis compared with controls when a histologic grading scale was used.. In this murine model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin were not effective in limiting hepatic injury after alpha-amanitin poisoning. Increases of aminotransferases and degrees of histologic hepatonecrosis were not attenuated by these antidotal therapies.

Topics: Acetylcysteine; Alanine Transaminase; Amanitins; Animals; Antidotes; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cimetidine; Disease Models, Animal; Male; Mice; Mushroom Poisoning; Penicillin G; Random Allocation; Silybin; Silymarin; Thioctic Acid

Topics: Amanitins; Creatinine; Emergency Medical Services; Humans; Liver Transplantation; Mushroom Poisoning; Predictive Value of Tests; Prothrombin

Topics: Adult; Age Factors; Aged; Amanita; Amanitins; Female; Humans; Japan; Male; Middle Aged; Mushroom Poisoning; Poison Control Centers; Seasons; Sex Factors; Time Factors

After consumption of mushrooms containing amatoxins (Amanita, Lepiota, and Galerina species), symptoms usually develop after a long delay (>6 h). Initial symptoms start as severe gastroenteritis, progressing to liver failure and possibly death as a result of hepatic coma. Since the survival rate of poisoned patients is claimed to depend on the time of beginning of efficient treatment, fast and reliable assays for amatoxins in biological fluids are essential. Described analytical methods for amatoxins include high performance liquid chromatography and radioimmunoassay (RIA). Recently, a new enzyme-linked immunosorbent assay (Bühlmann Amanitin ELISA kit) has been introduced as an alternative method to RIA. This ELISA-based assay offers several advantages: no complex extraction procedure is required (vs. HPLC) and no safety precautions concerning radioactivity have to be taken (vs. RIA). From August 2004 to October 2005, a pilot study was performed to test the practicability and the clinical utility of this method in emergency situations.. ten urines, 9 serums and 1 faeces from 10 patients suffering from acute gastroenteritis after mushroom ingestions (7 contaminated meals) were analyzed. Definitive diagnosis of amatoxin poisoning was made in 4 cases (3 contaminated meals) on the basis of the anamnesis, laboratory results, and clinical course. A patient developed a severe amatoxin poisoning with urinary amanitins level < 1.5 microg/L (urines were collected more than 72 h after mushroom ingestion). Two patients were paucisymptomatic with urinary amanitins levels >10 microg/L (urines were collected before the 36th hour).. Urine is the sample of choice for the determination of amatoxins. The most critical factor to invalidate the usefulness of this analysis is time. After 36 h, the sensitivity is unreliable.

Topics: Amanitins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Mushroom Poisoning; Phalloidine; Syndrome

The pathological effects of alpha-amanitin on BALB/c mice after receiving intravenous injection were evaluated by RP-HPLC and mouse genome oligonucleotide microarray. The content of alpha-amanitin in Amanita virosa was about 2833.8 microg/g dry fruiting body. The liver and kidneys showed critical pathological changes after alpha-amanitin poisoning, and sera BUN, Crea, ALT, AST, TBIL and DBIL were the sensitive markers. The compound alpha-amanitin was detected in liver and kidney tissue homogenates by RP-HPLC after 48 h. The results of mouse genome oligonucleotide microarray showed 146 genes' expression changed, which formed the alternant network. The expression of 66 genes decreased, while 80 ones increased with more than two-fold differential expression after 48 h. The compound alpha-amanitin influenced not only RNA polymerase II, but also the expression of its associated genes. The application of mouse oligo chip provided valuable data for further understanding the biological properties and molecular pathogenesis of alpha-amanitin, also might be helpful for screening the curative drug for alpha-amanitin intoxication.

Topics: Amanita; Amanitins; Animals; Down-Regulation; Gene Expression Regulation; Kidney; Liver; Male; Mice; Mice, Inbred BALB C; Mushroom Poisoning; Random Allocation

Topics: Amanitins; Humans; Liver Failure, Acute; Mushroom Poisoning

Indication of liver transplantation in acute liver failure following amatoxin intoxication is still uncertain.. One hundred and ninety-eight patients were studied retrospectively. The laboratory parameters alanine-aminotransferase, serum bilirubin, serum creatinine and prothrombin index were analyzed over time. Predictors of fatal outcome and survival were determined by receiver-operating-characteristic and sensitivity-specificity analysis.. Twenty-three patients died in the median 6.1 days (range, 2.7-13.9 days) after ingestion. Using a single parameter as predictor of fatal outcome the area under the receiver-operating-characteristic curve of prothrombin index (0.96) and serum creatinine (0.93) were both significantly greater (P<0.05) compared with serum bilirubin (0.82) and alanine-aminotransferase (0.69). Prediction of fatal outcome had an optimum, if a prothrombin index less than 25% was combined with a serum creatinine greater than 106 micromol/l from day 3 after ingestion onwards (sensitivity 100%, 95% confidence interval 87-100; specificity 98%, 95% confidence interval 94-100). The median time period between the first occurrence of this predictor in non-survivors and death was 63h (range, 3-230h).. A decision model of liver transplantation following amatoxin intoxication using prothrombin index in combination with serum creatinine from day 3 to 10 after ingestion enables an early and reliable assessment of outcome.

Topics: Adolescent; Adult; Alanine Transaminase; Amanitins; Bilirubin; Child; Humans; Liver Failure; Liver Transplantation; Mushroom Poisoning; Predictive Value of Tests; Prothrombin Time; Retrospective Studies; Survival Analysis

Amatoxin-containing species are responsible for the most severe cases of mushroom poisoning, with high mortality rate. Therefore, this poisoning should be ruled out in all patients presenting gastrointestinal symptoms after wild mushroom ingestion.. To determine sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficacy (DE) of urinary amanitin analysis in cases of suspected mushroom poisoning.. All cases of mushroom ingestion referred to a Poison Center during a one-month period were analyzed. Amanitin measurements were performed by ELISA method (functional least detectable dose 1.5 ng/ml; cut-off value not clearly established). Gastrointestinal symptoms latency and initial clinical assessment were considered alternative diagnostic tools. Definitive diagnosis was used as the reference standard.. Among 61 patients included in the study, amatoxin poisoning was diagnosed in 10 cases. Urine samples were collected 5.5 to 92 hours after mushroom ingestion. Urinary amanitin DE was 91.8%, 93.4%, and 80.3%, based on the cut-off value considered (1.5, 5.0, and 10.0 ng/ml, respectively). Symptoms latency longer than 6 hours and initial clinical assessment DE were 70.5% and 67.2%, respectively. To identify amatoxin poisoning, initial clinical assessment resulted more sensitive and urinary amanitin analysis more specific.. Urinary amanitin analysis is a valuable diagnostic tool and may significantly contribute to the management of suspected mushroom poisoning. At present, the best diagnostic accuracy can be obtained taking advantage of both the high sensitivity and negative predictive value of the clinical assessment performed by an experienced toxicologist, and the high specificity and positive predictive value that characterize urinary amanitin analysis.

Topics: Adult; Amanitins; Antibodies; Antidotes; Charcoal; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Mushroom Poisoning; Pilot Projects; Poison Control Centers; Radioimmunoassay; Reproducibility of Results; Transaminases

This paper presents species of fungi of high toxicity. Their consumption might have serious consequences for health and in many cases it might lead to death. Toxic compounds present in fungi have also been characterised, mechanisms of their toxic activity have been presented and clinical symptoms of poisoning have been described. Hallucinogenic mushrooms have also been mentioned as they have recently become a serious problem: many people use them to intoxicate themselves. There are also species of mushrooms that can be consumed under certain conditions since they can occasionally trigger off serious disturbances for the functioning of organisms.

Topics: Amanita; Amanitins; Cross-Sectional Studies; Humans; Incidence; Mushroom Poisoning; Peptides, Cyclic; Poland; Structure-Activity Relationship

Experiences of liver transplantation after Amanita phalloides poisoning were analysed in anaesthetic and intensive therapist point of view based on 3 cases. Cardiac problems were found at all patients during the postoperative period. Probably the amatoxin has cardiotoxic effect or a part of phallotoxins are absorbed despite cooking and caused reversible cardiac function impairment. Pancreatitis, DIC, gastrointestinal bleeding, acute renal failure were found at all patients, therefore liver transplantation is only a part of the treatment, complex therapy is necessary in this cases.

Topics: Acute Kidney Injury; Adult; Amanita; Amanitins; Anesthesia, General; Child; Combined Modality Therapy; Critical Care; Disseminated Intravascular Coagulation; Electrocardiography; Gastrointestinal Hemorrhage; Heart Conduction System; Humans; Liver Failure; Liver Transplantation; Male; Mushroom Poisoning; Pancreatitis

The clinical picture of Amanita phalloides poisoning includes hypoglycaemia, usually related to hepatic damage. In fact, Amanita toxins induce hepatic glycogen depletion in humans and animals. However, in animals morphological changes of pancreatic beta cells are reported, suggesting that an alteration of insulin secretion might be involved in the pathogenesis of hypoglycaemia. Therefore, we determined fasting glucose, insulin and C-peptide levels in ten patients intoxicated by Amanita phalloides and in ten control subjects. Fasting blood samples were drawn on 3 consecutive days, beginning 48-72 h after mushroom ingestion, and glucose, insulin and C-peptide concentrations were determined by routine methods. Serum glucose concentrations did not differ between poisoned subjects and controls, whereas insulin and C-peptide concentrations were significantly higher in poisoned subjects ( P<0.01), with a significant positive correlation ( R=0.97, P<0.001). We also evaluated the effects of alpha-amanitin, the main amatoxin, on in vitro insulin release. Rat islets were incubated with 5 and 50 mg/l alpha-amanitin, in the presence or absence of 5.6 mM glucose. In another protocol, islets were preincubated for 2 h with 5 and 50 mg/l alpha-amanitin in medium containing 5.6 mM glucose. After lavage, islets were incubated with increasing glucose (2.8-22.0 mM) to evaluate insulin release. In vitro, both concentrations of toxin induced insulin release (5 mg/l P<0.02, 50 mg/l P<0.01 vs controls), in the presence of 5.6 mM glucose. Islets preincubated with 5 mg/l alpha-amanitin showed a pattern of glucose-stimulated insulin release similar to controls, whereas islets preincubated with 50 mg/l alpha-amanitin showed an increased basal release with a reduced response to glucose stimulation. These observations show that Amanita toxins might play a role in the clinical context of Amanita poisoning. We demonstrate, for the first time, that alpha-amanitin induces insulin release and may exert a cytotoxic effect on beta cells.

Topics: Adult; Amanita; Amanitins; Animals; Blood Glucose; C-Peptide; Female; Humans; In Vitro Techniques; Insulin; Islets of Langerhans; Male; Mushroom Poisoning; Rats; Rats, Wistar; Toxins, Biological

In the past 10 years from 1991 to 2000, the number of consultations to the Japan Poison Information Center were 947 concerning mushroom poisonings. However, those from the hospital cases were not analyzed toxicologically. We examined toxicologically 20 cases (35 patients) of mushroom poisonings from 1993 to 2001. Investigation of amanita toxin poisoning was requested in 19 cases. We could detect the amanita toxin, amanitin, and phalloidin, in two cases, which resulted in concluding the cause of death. A fatal case by the magic mushroom poisoning was analyzed in the blood, urine, and mushroom, and we detected the hallucinogenic substances from the body fluids and ingested mushrooms. We report the results of our examinations, and point out the usefulness of the examination of the mushroom itself and biological samples toxicologically for forensic practice.

Topics: Adult; Aged; Amanita; Amanitins; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Humans; Japan; Male; Mushroom Poisoning; Phalloidine

Topics: Adolescent; Adult; Amanita; Amanitins; Child; Child, Preschool; Female; Hemoperfusion; Humans; Liver Diseases; Liver, Artificial; Male; Mushroom Poisoning; Plasma Exchange; Sorption Detoxification

Topics: Adolescent; Adult; Amanita; Amanitins; Female; Humans; Liver Transplantation; Male; Mushroom Poisoning; Mycotoxins; Nuclear Family

Although some Japanese Galerina species poisonings manifest as gastrointestinal symptoms followed by late-onset hepatorenal failure (phalloides syndrome), the toxin responsible for this has not been determined.. We report a 6-year-old boy who developed characteristic cholera-like diarrhea and late-onset severe hepatic deterioration after eating mushrooms, later identified as a Galerina species, most likely Galerina fasciculata. A residual mushroom revealed alpha-amanitin. This account is the first known reported case of poisoning by Japanese Galerina species where an amatoxin was demonstrated to be responsible for the toxicity.

Topics: Agaricales; Amanitins; Child; Diarrhea; Humans; Liver Failure; Liver Function Tests; Male; Mushroom Poisoning; Spectrophotometry, Ultraviolet

We report the first case of a lethal Amanita phalloides intoxication from stored mushrooms. After picking the mushrooms were kept in a freezer for 7-8 months. This case is in accordance with the well-known stability of the amatoxins and demonstrates the possibility of A. phalloides poisoning at any time of year.

Topics: Amanita; Amanitins; Fatal Outcome; Female; Frozen Foods; Humans; Middle Aged; Mushroom Poisoning; Switzerland

Amanita phalloides mushrooms are extremely toxic. A variety of treatments have been proposed based as often on anecdotal experience as on firm evidence. General consensus exists regarding some treatments, such as the use of silibinin, penicillin, and activated charcoal. The most polarized debate concerns the value of extracorporeal elimination. We describe a case of 2 adults with confirmed Amanita phalloides poisoning treated with hemodialysis (HD) immediately after arrival at our tertiary care hospital (23 h after ingestion) and later with hemoperfusion (HP); a series blood samples were taken to determine the clearance of the toxin by each method. No amatoxin was detected before treatment, after treatment, or in the HD/HP circuits. Neither HD nor HP contributed to the clearance of amatoxin.

Topics: Adult; Alanine Transaminase; Amanita; Amanitins; Aspartate Aminotransferases; Female; Hemoperfusion; Humans; Male; Mushroom Poisoning; Renal Dialysis; Treatment Outcome

We report here three cases of Amanita virosa induced toxic hepatitis. Two of the three cases recovered but the other died 10 days after mushroom ingestion. Since the mortality of Amanita mushroom induced toxic hepatitis is very high, prompt diagnosis and aggressive therapeutic measures should be initiated as soon as possible. Our cases showed that the initial serum aminotransferase levels might not predict the clinical outcome of the patient, but that the prothrombin time (PT) seemed to be a more useful prognostic marker. Close monitoring of aminotransferase levels and PT as well as appropriate therapy are recommended. All three cases showed signs of proteinuria and we were able to characterize mixed tubular and glomerular type proteinuria at 3 or 4 days after ingestion in two cases. Among the previously reported Korean cases of suspected Amanita induced toxic hepatitis, most species could not be identified except for four cases of Amanita virosa. No cases of Amanita phalloides induced toxic hepatitis have been identified in Korea so far.

Topics: Adult; Amanita; Amanitins; Chemical and Drug Induced Liver Injury; Female; Humans; Male; Middle Aged; Mushroom Poisoning; Proteinuria

The objective of the present study was to develop and validate a liquid chromatographic method with electrochemical detection to measure alpha amanitin concentrations in urine after sample pretreatment with double mechanism (reversed phase/cation exchange) solid-phase extraction cartridges. The urine samples (10 ml) were purified and concentrated to 1 ml with elimination of matrix contaminants. The extracts were then separated by isocratic reversed-phase chromatography using a C18 column (4.6 mm x 25 cm) with a mobile phase composed of 0.005 M phosphate buffer (pH 7.2) and acetonitrile (90:10). Coulometric detection was performed by applying an oxidation potential of +500 mV to a porous graphite electrode in a low-volume analytical cell. The limit of quantitation was 10 ng/ml with a signal-to-noise ratio = 25. The linearity studied on spiked urine was satisfactory (r = 0.9966) from 10 ng/ml to 200 ng/ml. The average extraction recovery of alpha amanitin was 78%, determined using spiked urine samples ranging from 10-300 ng/ml. The intra-assay precision was checked at 10, 50 and 100 ng/ml levels (n = 10) in spiked urine samples, with resulting coefficients of variation of 3.6%, 2% and 1.5%, respectively.

Topics: Amanitins; Chromatography, High Pressure Liquid; Forensic Medicine; Humans; Mushroom Poisoning; Reproducibility of Results

Topics: Adolescent; Adult; Aged; Amanita; Amanitins; California; Cause of Death; Charcoal; Child; Colic; Diarrhea; Female; Fluid Therapy; Histamine H2 Antagonists; Humans; Male; Middle Aged; Mushroom Poisoning; Nausea; Vomiting

The authors carried out sixteen hemoperfusions with alpha-amanitin in vitro in a closed system using active charcoal, Amberlite XAD-2 and Amberlite XAD-4 in hemoperfusion capsules. As a perfusion solution 4 liters of 0.9% NaCl solution was used. The alpha-amanitin concentration in the solution was 8.3 +/- 0.36 mg/L. Individual hemoperfusion lasted 5 hours. Two hundred and forty minutes of Amberlite XAD-2 hemoperfusion led to the zero values of alpha-amanitin concentration in 0.9% NaCl solution. When using active charcoal the adsorption capacity of the hemoperfusion capsule was already exhausted at 120 min. The results gathered suggest that the most effective alpha-amanitin hemoperfusion in vitro was obtained with Amberlite XAD-2 and the least effective with active charcoal. The authors recommend the use of hemoperfusion with Amberlite XAD-2 for acute intoxication with Amanita phalloides in humans up to 24-36 hours after poisoning.

Topics: Adsorption; Amanitins; Charcoal; Dialysis Solutions; Hemoperfusion; Humans; In Vitro Techniques; Mushroom Poisoning; Particle Size; Resins, Synthetic; Sodium Chloride

Over 90% of the lethal cases of mushroom toxin poisoning in man are caused by a species of amanita. The amatoxins (especially alpha- and beta-amanitin) found in amanita deserve special attention, because of their high pharmacological potency, their high natural concentration and their high chemical and thermal stability. Measures can be taken to improve the survival rates (aggressive gastroenteric decontamination, liver protection therapy) if the poisoning is diagnosed correctly and as early as possible. The standard assay for alpha-amanitin is a radioimmunoassay (RIA). Among other reagents, this assay uses 125I-labelled alpha-amaintin, which has a low shelf life. The assay is therefore not available at all hospitals and all year round. In this paper, a first attempt to employ capillary zone electrophoresis (CZE) to quantify amatoxins alpha- and beta-amanitin in urine samples of afflicted patients and in toadstool extracts is described. Diode array detection is used for identification of the resolved substances in the electropherogram. An analysis requires 20 min. The detection limit is 1 microgram/ml, i.e., 5 pg absolute. Relative standard deviations are between 1 and 2% for the calibration standards (peak height and area) and ca. 7.5% for the real samples. Advantages of the CZE over the RIA include lower cost, the possibility of quantifying several toxins in one analysis, less consumption of potentially harmful reagents (no radio-labelled substances, no addition of alpha-amanitin as reagent) and, most importantly, all-year-round availability of the assay. The detection limit is still somewhat high and does not cover the entire clinically relevant range. Attempts to lower the detection limit by the necessary order of magnitude are currently under way in our laboratory. These include application of laser-induced fluorescence detection, liquid chromatography-CZE and CZE-mass spectrometry techniques.

Topics: Amanita; Amanitins; Chemistry, Clinical; Electrophoresis, Capillary; Humans; Mushroom Poisoning; Reference Standards; Reproducibility of Results; Spectrophotometry, Ultraviolet

Four cases of severe Lepiota poisoning, including three which developed toxic fulminant hepatitis treated by orthotopic hepatic transplantation, are reported here. The toxicity of the Lepiota is discussed as well as the indications for hepatic transplantation in poisonings due to amatoxin-containing mushrooms.

Topics: Adult; Amanitins; Child; Electroencephalography; Female; Humans; Liver Failure; Liver Transplantation; Male; Mushroom Poisoning

Amanita phalloides is responsible for about 90 per cent of all fatal cases of mushroom intoxication. The amatoxins, the main toxic component of these fungi, are responsible for gastro-intestinal symptoms as well as hepatic and renal failure. Three brothers with Amanita phalloides poisoning were admitted with gastro-intestinal symptoms beginning 12 h after ingestion. Jaundice, hepatomegaly and neurological symptoms were not present, but liver enzymes were moderately increased. Alfa-amanitin was detected in sera of all patients. All patients underwent charcoal hemoperfusion and two of them had additional hemodialysis along with conservative therapy. Liver enzymes that showed a marked increase on the second day of therapy decreased to normal levels on the 28th day. All of our patients survived. This life saving role of early haemoperfusion in Amanita phalloides poisoning is emphasized.

Topics: Adolescent; Amanita; Amanitins; Charcoal; Child; Diagnosis, Differential; Hemoperfusion; Humans; Male; Mushroom Poisoning; Turkey

We report four cases of poisoning with amatoxin-producing mushrooms in suburban Long Island. All occurred when amateur mushroom hunters picked mushrooms from neighboring lawns. Two patients presented 30 hours post ingestion with evidence of acute hepatic dysfunction. One survived, after treatment with charcoal and penicillin; the other, a 90-year-old woman with prior cardiac disease soon developed shock and subsequently died. The other two patients were admitted 18 hours after ingestion of Lepiota chlorophyllum and received prompt charcoal hemoperfusion. Both did well, although one had a mild elevation of transaminases. Although most reports of amatoxin poisoning originate in Europe, these cases confirm that amatoxin-producing mushrooms, including Lepiota chlorophyllum, may be found in northeastern American suburbs. Such patients who present prior to 24 hours after ingestion should receive charcoal hemoperfusion if a lethal dose (> 50 g of mushroom) has been eaten.

Topics: Adult; Aged; Aged, 80 and over; Amanita; Amanitins; Basidiomycota; Fatal Outcome; Female; Heart Block; Humans; Hypertension; Male; Middle Aged; Mushroom Poisoning; New York; Thyroiditis, Autoimmune

Alpha-amanitin, the main toxin of the death cap fungus (Amanita phalloides) is one of the most dangerous natural poison. This toxin damages eukaryotic cells by inhibiting their transcription. Lesions are seen in cells with rapid protein synthesis, particular in liver and renal cells, even at low toxin concentrations. Without adequate intensive therapy, the outcome of alpha-amanitin poisoning is very poor. This article reports various courses of amanitin intoxication in a family. In 3/4 patients, severe hepatic failure developed as assessed by a decrease of all coagulation factors, mainly Quick's test and factor V (< 10%-15%). Despite vigorous replacement of coagulation factors, in 1 of the patients orthotopic liver transplantation had to be performed on day 4, whereas in all other patients liver function improved spontaneously. All patients survived their intoxication. Both the pharmacological basis and clinical manifestations of Amanita intoxication are discussed. On this basis a treatment scheme is presented which the authors believe may be useful to clinicians.

Topics: Adult; Aged; Amanita; Amanitins; Child, Preschool; Critical Care; Emigration and Immigration; Female; Germany; Hepatic Encephalopathy; Humans; Liver Function Tests; Liver Transplantation; Male; Mushroom Poisoning; Russia

Mushroom poisonings caused by amatoxins are mostly lethal. Information about mycetisms caused by white species of Amanita is scarce. The present paper describes a case of mushroom poisoning caused by A. virosa. A prolongated latency period (6-10 hours), followed by cholera-like, improvement and visceral complication phases confirmed the amatoxin poisoning. The consumption of about 3 pounds of the toadstool by seven persons caused the death of five. Two patients survive the ingestion.

Topics: Adolescent; Adult; Aged; Amanita; Amanitins; Fatal Outcome; Female; Humans; Male; Mexico; Mushroom Poisoning

Twelve patients with Galerina Autumnalis (GA) poisoning were treated. Amatoxin and phallotoxin are the principal toxins of GA. After absorption from intestine into the liver, the toxins combine with RNA polymerase, resulting in block of messenger (mRNA) synthesis, hepatocellular damage, hepatitis, hepatic necrosis, serious coagulation abnormalities and DIC. The clinical characteristics are long latent period, short period of "pseudo-remission" and serious liver dysfunction. These were pathologically confirmed by autopsy. Our experiences with this poisoning are as follows: treatment should be carried out as early as possible, especially with gastric lavage and catharsis and special attention paid to the "pseudo-remission".

Topics: Adolescent; Adult; Agaricales; Amanitins; Child; Female; Gastric Lavage; Humans; Liver; Male; Mushroom Poisoning; Necrosis

The kinetics of alpha and beta amanitin were studied in 45 patients intoxicated with Amanita Phalloides. The amatoxins were analyzed by high performance liquid chromatography in plasma (43 cases), urine (35 cases), gastroduodenal fluid (12 cases), feces (12 cases) and tissues (4 cases). All patients had gastrointestinal symptoms and 43 developed an acute hepatitis. Two patients underwent successful liver transplantation. Eight patients, of whom three were children, died. The detection of amatoxins in the biological fluids was time dependent. The first sample was obtained at an average of 37.9 h post ingestion in the patients with positive results and at 70.6 h in the samples without detectable amatoxins. Plasma amatoxins were detected in 11 cases at 8 to 190 ng/mL for alpha and between 23.5 to 162 ng/mL for beta. In 23 cases amatoxins were detected in urine with a mean excretion per hour of 32.18 micrograms for alpha and 80.15 micrograms for beta. In 10 patients the total amounts eliminated in the feces (time variable) ranged between 8.4 and 152 micrograms for alpha amanitin and between 4.2 and 6270 micrograms for beta amanitin. In three of four cases amatoxins were still present in the liver and the kidney after day 5. Amatoxins were usually detectable in plasma before 36 h but were present in the urine until day 4. The rapid clearance indicates that enhanced elimination of amatoxins requires early treatment. Clearance of circulating amatoxins by day 4 spares the transplanted liver.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amanita; Amanitins; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Liver Function Tests; Liver Transplantation; Male; Metabolic Clearance Rate; Middle Aged; Mushroom Poisoning; Prognosis; Time Factors; Tissue Distribution

Mushrooms of the genus Lepiota (helveola and bruneo-incarnata), similar to those of the genus Amanita, contain amatoxins. Amatoxins, especially amanitin, cause cellular destruction by inhibiting RNA polymerase. Due to the hepatic toxicity of these mushrooms, we have assessed their incidence on alkaline phosphatase levels and on its isoenzymes. Total alkaline phosphatase activity levels were not found to be increased except in two patients, and then only moderately. As regards isoenzymes, the occurrence of a double hepatic fraction in five of the 10 patients, is the most remarkable finding. There seems to exist a relatively close correspondence between the occurrence of a hepatic2 fraction correlating with those of urine amanitin. We conclude that the hepatic2 fraction proves to be important in assessing liver damage by mushroom poisoning because of its correlation with the patient's degree of poisoning.

Topics: Alanine Transaminase; Alkaline Phosphatase; Amanitins; Chemical and Drug Induced Liver Injury; Electrophoresis; Humans; Isoenzymes; Mushroom Poisoning; Prognosis; Regression Analysis

Forty-eight hours after a women was poisoned by ingesting Amanita phalloides mushrooms, she developed fulminant hepatic failure with collapse, pH 7.24, lactic acidosis 7.6 mmol/l, hypoglycaemia 3.5 mmol/l, anuria and stage IV coma requiring tracheal intubation and mechanical ventilation. Transaminase level was up to 8,000 UI/l. Prothrombin and factor V levels were below 10 percent, with an APT time of 86 s versus a 29 s control time. Twenty-four hours after her admission, the patient underwent orthotopic liver transplantation. The postoperative period was uneventful, with return to consciousness and rapid normalization of hepatic biochemistry values, without signs of acute rejection. This 10th published case of orthotopic liver transplantation for Amanita phalloides poisoning with acute hepatic necrosis confirms that this type of treatment must be systematically envisaged in all such cases.

Topics: Amanita; Amanitins; Chemical and Drug Induced Liver Injury; Female; Humans; Liver Transplantation; Middle Aged; Mushroom Poisoning; Phalloidine

Topics: Acute Disease; Adolescent; Adult; Amanitins; Disseminated Intravascular Coagulation; Female; Hepatic Encephalopathy; Hepatitis; Humans; Liver; Male; Mushroom Poisoning

Topics: Acute Disease; Amanita; Amanitins; Child, Preschool; Gallbladder; Humans; Male; Mushroom Poisoning; Phalloidine; Ultrasonography

Ingestion of mushrooms followed after 6-12 hours by gastrointestinal symptoms and after 3-4 days by hepatic symptoms is diagnostic for the life-threatening amatoxin intoxication and should be treated as soon as possible. Four case histories are reported and recommendations for treatment are given.

Topics: Acute Kidney Injury; Adult; Amanita; Amanitins; Combined Modality Therapy; Female; Humans; Liver Function Tests; Male; Middle Aged; Mushroom Poisoning

Twenty-seven consecutive mushroom poisoning cases were followed up over a period of 14 days. Fourteen out of 27 died of liver failure. There were no deaths from renal failure. The mushrooms were identified as the amatoxin-containing Lepiota species. Therapeutic measures included nasogastric lavage, charcoal, vitamin C, vitamin B, penicillin G, corticosteroids, oral streptomycin and, in the case of a few patients, limited amounts of thioctic acid. Of the ten haemodialysed, nine died. Unfortunately charcoal haemoperfusion was not available. It appeared that therapeutic measures were ineffective and it also seemed that the amount of mushroom ingested was the determining factor for the prognosis. An important point to make is that renal failure does not occur and liver failure is always delayed (group II). For this reason all suspected cases of mushroom poisoning, regardless of absence of clinical signs and symptoms, must be hospitalised for a period of at least one week. The poisonous properties of wild mushrooms have been recognized since ancient times. However, despite awareness of their inherent dangers, serious poisoning continues to occur. Fatal intoxications can be attributed almost entirely to the amtoxin-containing species. Amanita phalloides have been blamed for over 90% of poisoning deaths in North America. There are reports of intoxications of other amatoxin-containing species in Europe, but fatalities due to Lepiota species are reported only rarely. It was previously acknowledged that the interval between ingestion of mushrooms and the onset of symptoms is longer than expected in serious poisonings.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Amanitins; Chemical and Drug Induced Liver Injury; Child; Coma; Female; Humans; Male; Middle Aged; Mushroom Poisoning; Prognosis; Renal Dialysis; Thioctic Acid; Time Factors

In 1986-88, 46 poisonings (4 of which were fatal) caused by amatoxin mushroom were reported. The fatalities were males aged between 7 and 65 years. They all had gastrointestinal symptoms and three of the patients died of acute hepatic insufficiency. The fourth died as a result of an intestinal perforation. The clinical and pathological alterations are compared with the findings of other authors.

Topics: Adolescent; Adult; Aged; Amanitins; Child; Humans; Male; Mushroom Poisoning; Spain

A monoclonal antibody, with high affinity against the mushroom toxin alpha-amanitin, was prepared. Administration of the Fab fragment of the monoclonal antibody to mice caused a 50-fold increase in alpha-amanitin toxicity. Electron micrographs showed normal appearance of hepatocytes but typical, amanitin-induced lesions in cells of the proximal convoluted tubules of the kidney. The pronounced nephrotoxicity is mainly explained by glomerular filtration and tubular reabsorption of the Fab-amatoxin complex and, to a lesser extent, of the immunoglobulin-amatoxin complex, which is still c. Twice as toxic as free alpha-amanitin. To our knowledge this is the first reported case where immunoglobulins or their fragments enhance rather than decrease the activity of a toxin. Accordingly, immunotherapy of Amanita mushroom poisoning in humans does not appear promising.

Topics: Amanitins; Animals; Antibodies, Monoclonal; Female; Immunoglobulin Fab Fragments; Kidney Tubules; Mice; Mice, Inbred Strains; Microscopy, Electron; Mushroom Poisoning

A reversed-phase high-performance liquid chromatographic assay has been developed for the simultaneous determination of alpha-amanitin and phalloidin in human plasma. The procedure is based on the enrichment of the toxins on a pre-column, followed by the transfer of both compounds in a foreflush mode to the analytical column. alpha-Amanitin and phalloidin can be quantified reliably down to a minimum concentration of 10 ng/ml in plasma (relative standard deviation less than 10%). An alternative method is recommended for hepatic coma patients.

Topics: Agaricales; Amanita; Amanitins; Child; Humans; Indicators and Reagents; Mushroom Poisoning; Oligopeptides; Phalloidine; Solvents

It is possible to determine the management and prognosis of mushroom poisoning from the history and initial symptoms with a high degree of confidence. The most important intoxications are those involving Amanita phalloides or other potentially fatal amatoxin-containing mushrooms, which have a latent period of ten to 12 hours before the patient becomes symptomatic. Because aggressive gastroenteric decontamination can reduce the extent of hepatic damage, it is important to attempt to determine during this asymptomatic period whether amatoxin exposure has occurred. Various laboratory methods that might be useful are reviewed.

Topics: Amanita; Amanitins; Basidiomycota; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Diagnosis, Differential; Humans; Mushroom Poisoning; North America; Radioimmunoassay; Spores, Fungal; Time Factors

Topics: Amanita; Amanitins; Humans; Mushroom Poisoning

In contrast to popular opinion phallotoxins do not play a role in poisoning with Amanita phalloides when the fungi are ingested orally. All toxic properties of this mushroom are due to amatoxins which, in contrast to the phallotoxins, are absorbed upon ingestion. Nearly all experiments on intact animals were performed by parenteral injection of phalloidin and therefore, most of these are unsuitable for practical consideration. In the present survey, however, a series of important findings are discussed, which provide insight into various functions of liver cells. When present in the blood, phalloidin and other phallotoxins are selectively taken up by hepatocytes. No other types of cells are sensitive to the toxin. No extrahepatic tissue is primarily impaired by phalloidin. Phalloidin cannot be degraded by peptidases or by proteases occurring in animals. Phalloidin is therefore a useful model substance for studies on the uptake of cyclopeptides by liver cells. The carrier system responsible for the active uptake of phalloidin can also translocate antamanide and several cyclic modifications of somatostatin. Phallotoxins bind with high affinity to microfilamentous structures, in particular to F-actin [Govindan et al., Naturwissenschaften, 59 (1972) 521-522] whereas phallotoxins are not bound to the monomer (G-actin). With respect to the strong organotropism of phallotoxins, intravenously injected phalloidin binds preferentially to microfilamentous F-actin of hepatocytes. Phalloidin is therefore a tool for inactivation of microfilamentous functions specifically in liver cells, and is suitable as a prototype of a cholestatic agent. In perfused livers arrest of bile flow is the earliest effect seen after addition of the toxin. In cells from other tissues phalloidin is only toxic when applied by intracellular microinjection. Phalloidin poisoning has been often used as a model for liver damage in the testing of hepatoprotective drugs. This substance is, however, not useful for such studies since the mechanism of phalloidin poisoning is too specific for interpretation in the sense of general liver protection.

Topics: Actin Cytoskeleton; Amanita; Amanitins; Animals; Bile; Chemical Phenomena; Chemistry; Liver; Mice; Mushroom Poisoning; Oligopeptides; Phalloidine; Rats

Topics: Amanita; Amanitins; Humans; Mushroom Poisoning

Twenty-two patients who ate mushrooms containing hepatotoxic amatoxins were treated during the fall and winter seasons of 1982 and 1983. All patients were treated with intensive supportive care and repeated oral doses of activated charcoal. In two patients fulminant hepatic failure developed and they died. One patient in whom encephalopathy developed had an orthotopic liver transplant and survived. Liver biopsy specimens obtained from five patients during the acute illness showed centrilobular hemorrhagic necrosis. The hepatic histopathology in a biopsy specimen from a 5-year-old boy eight weeks after mushrooms were eaten showed bands of fibrosis and islands of hepatocytes suggestive of early cirrhosis. Radioimmunoassay for amanitins, done on the serum from all patients, detected the toxins in only three, probably because most of the specimens were obtained 24 hours or more after the ingestion. This series, with a mortality rate of 9%, illustrates the outcome in patients who receive intensive supportive care and provides a background on which success of specific treatments should be judged.

Topics: Adolescent; Adult; Aged; Amanitins; California; Charcoal; Child; Child, Preschool; Female; Hemoperfusion; Humans; Male; Middle Aged; Mushroom Poisoning

Topics: Amanitins; Humans; Mushroom Poisoning

Amatoxins were detected radioimmunologically as early as 90-120 min after ingestion in the gastric fluid and urine of a 15-year-old boy who tried to commit suicide by ingestion of wild mushrooms. This early detection of amatoxins in the urine is proof of rapid absorption from the intestinal tract and subsequent excretion by the kidneys in man.

Topics: Adolescent; Amanita; Amanitins; Gastric Juice; Humans; Male; Mushroom Poisoning; Radioimmunoassay

The mushroom Lepiota josserandii Bon and Boif. has been identified as the cause of an unintentional, fatal intoxication in New York. The course of the symptoms, beginning with a 9 h latent period, was similar to what would be expected in a case of Amanita phalloides-type intoxication. Despite supportive medical care the victim expired 110 h after ingestion. Thin layer chromatography detected the presence of alpha- and gamma-amanitin and radioimmunoassay confirmed a level of 3.5 mg/gm dry weight of amatoxins in mushrooms from the same location.

Topics: Agaricales; Amanitins; Chromatography, Thin Layer; Humans; Male; Middle Aged; Mushroom Poisoning; New York; Radioimmunoassay

Topics: Adolescent; Aged; Amanita; Amanitins; Diuresis; Female; Humans; Male; Middle Aged; Mushroom Poisoning; Radioimmunoassay

Topics: Amanita; Amanitins; Chemical and Drug Induced Liver Injury; Female; Humans; Kidney Diseases; Middle Aged; Mushroom Poisoning

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Amanita; Amanitins; Critical Care; Female; Hepatic Encephalopathy; Humans; Male; Middle Aged; Mushroom Poisoning; Prognosis

Four incidents of mushroom poisoning, representing four of the seven established groups of toxic mushrooms, are presented. These case reports illustrate the range of gastrointestinal and neurological symptoms caused by mushroom poisoning and reflect a nationwide increase in reports of serious poisonings in recent years. Severity of poisonings often parallels the time span between consumption and onset of symptoms, with serious poisonings having longer incubation periods. New therapies for amatoxin poisoning may reduce mortality caused by these poisonings.

Topics: Acute Kidney Injury; Adult; Aged; Amanitins; Child; Diarrhea; Female; Hallucinations; Humans; Male; Middle Aged; Mushroom Poisoning; New York; Respiratory Distress Syndrome; Thioctic Acid; Time Factors

Survival of mice after lethal doses of a lyophilizate from Amanita phalloides ('death cap') was markedly increased by single doses of ethanol applied 30 min before or 5 min after the mushroom. Hepatic histopathological damage (confluent necrosis) was largely prevented. Acute, but not chronic, consumption of ethanol may thus influence favorably the outcome of death cap poisoning and should be taken into consideration in the evaluation of therapeutic measures.

Topics: Amanita; Amanitins; Animals; Drug Interactions; Ethanol; Female; Liver; Mice; Mushroom Poisoning; Mycotoxins; Phalloidine

Topics: Amanitins; Humans; Mushroom Poisoning; Pyridoxine

Topics: Amanita; Amanitins; Animals; Humans; Kinetics; Lethal Dose 50; Mushroom Poisoning

Topics: Adult; Amanita; Amanitins; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Mushroom Poisoning; Pregnancy; Pregnancy Complications

Topics: Adult; Amanita; Amanitins; Humans; Male; Mushroom Poisoning

Topics: Adolescent; Adult; Aged; Amanita; Amanitins; Child; Child, Preschool; Fluid Therapy; Humans; Hyperbaric Oxygenation; Middle Aged; Mushroom Poisoning; Penicillin G; Prognosis; Silymarin; Time Factors

Topics: Amanita; Amanitins; Chromatography, High Pressure Liquid; Humans; Mushroom Poisoning

Topics: Amanitins; Antidotes; Cyclopropanes; Gastric Lavage; Glutamine; Humans; Monomethylhydrazine; Muscarine; Muscimol; Mushroom Poisoning; Psilocybin

Topics: Amanita; Amanitins; Humans; Liver; Mushroom Poisoning; Mycotoxins; Phalloidine

Topics: Adolescent; Adult; Aged; Amanitins; Antitoxins; Female; Gastric Lavage; Humans; Male; Middle Aged; Mushroom Poisoning; Peritoneal Dialysis

Topics: Amanitins; Child; Humans; Hungary; Mushroom Poisoning

Topics: Amanita; Amanitins; Humans; Mushroom Poisoning

Topics: Amanitins; Humans; Mushroom Poisoning

Topics: Amanita; Amanitins; Diuretics; Humans; Mushroom Poisoning

In a 3 year period (1975-77) 50 patients have been admitted to the I.C.U. of Polyclinic Hospital of Milan for poisoning from mushrooms of Amanita genus. In 47 cases the diagnosis was confirmed "a posteriori" by serum or urinary detection of amtoxins and/or by clinical evidence of typical liver injury. Besides the symptomatologic support, the therapeutic treatment included combined removal procedures, such as peritoneal dialysis, plasmapheresis, forced diuresis. The detection by radioimmunoassay of amatoxins [6] in the serum and in the urine of these patients proves that this therapeutic treatment can be effective within about 36 hours from ingestion time. The intensive medical care and the removal approach yielded as the whole favourable results in our patients (overall mortality was 6 patients, i.e. 12,7%). It should moreover be emphasized that of the 35 patients, who had been treated with early removal techniques, 12 with ascertained amanita poisoning, had neither clinical nor biochemical evidence of hepatic damage; 14 had a moderate liver damage; 9 experienced a severe liver failure and hepatic coma occurred in 4 of the latter. These poor results can be ascribed to the severity of the poisoning as well as to a peculiar kinetic of amatoxins in each subject.

Topics: Adolescent; Adult; Aged; Amanita; Amanitins; Child; Child, Preschool; Diuretics; Female; Humans; Liver; Male; Middle Aged; Mushroom Poisoning; Peritoneal Dialysis; Plasmapheresis; Radioimmunoassay

Topics: Amanita; Amanitins; Animals; Body Fluids; Dogs; Gastric Mucosa; Humans; Intestinal Mucosa; Mushroom Poisoning

An analysis of 28 cases of amanita phalloides poisoning serves as basis for a discussion of the clinical features and therapeutic problems involved. A critical review of recent experimental investigations in animals points to new possibilities in the treatment of amanita phalloides poisoning.

Topics: Adult; Amanita; Amanitins; Austria; Chemical and Drug Induced Liver Injury; Child; Exchange Transfusion, Whole Blood; Female; Humans; Male; Mushroom Poisoning; Phalloidine; Prothrombin; Renal Dialysis; Vitamin K

Topics: Amanita; Amanitins; Charcoal; Chloramphenicol; Diuretics; Female; Gastric Lavage; Hemoperfusion; Humans; Middle Aged; Mushroom Poisoning; Penicillins; Sulfamethoxazole; Thiosulfates

Cases of intoxication with Amanita phalloides are analyzed in the 17-year-period-material of the Department of the Forensic Medicine of the Semmelweis Medical University and the Department of the Urgent Internal Diseases of the Municipal Korányi Sándor and Frigyes Hospital. The findings show that the number of intoxication with mushrooms during the last years increased. Pahtomorphological changes were also analyzed. Results of the treatment in intensive care units are also discussed.

Topics: Agaricales; Amanita; Amanitins; Humans; Hungary; Mushroom Poisoning

Topics: Amanitins; Humans; Mushroom Poisoning; Penicillins; Protein Binding; Serum Albumin

The curative potencies of cytochrome c applied 8 hours after lethal doses of alpha-amanitin in mice are confirmed. In a comprehensive series of experiments, various dosage schedules were explored. Optimal effects with cure rates approaching 100% were obtained either with repeated doses of cytochrome c or by combining it with penicillin. Male mice are more sensitive to alpha-amanitin than female mice but it was established that the antidote is effective in both sexes. Substantial cure rates are seen even when the treatment after supralethal doses of alpha-amanitin is withheld for 12 hours after the poisoning.

Topics: Amanita; Amanitins; Animals; Cytochrome c Group; Drug Synergism; Female; Male; Mice; Mice, Inbred CBA; Mushroom Poisoning; Penicillin G; Sex Factors

Topics: 4-Aminobenzoic Acid; Amanitins; Amino Acids, Sulfur; Aminobenzoates; Aminocaproates; Aminocaproic Acid; Animals; Antidotes; Benzopyrans; Catechin; Flavonoids; Mice; Mushroom Poisoning; Oligopeptides; Phalloidine; Pyridines; Silymarin; Tiopronin

The effectiveness of three plasma cleansing techniques (exchange transfusion, peritoneal dialysis and plasmapheresis) is studied in the treatment of phalloides intoxication. The severity of the latter is dependent upon the amount of toxin ingested, with can now be measured by radio-immunology, as well as the fixation of the toxin in the liver. Methods to ensure its elimination must be instituted as soon as possible. Thus in 43 patients who had consumed more than 50 g of fresh fungi, there were no deaths amongst those treated during the first 36 hours and 7 deaths out of 22 patients treated late. It is not yet possible to define the respective values of each method.

Topics: Adolescent; Adult; Agaricales; Aged; Amanita; Amanitins; Blood Transfusion; Body Weight; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Mushroom Poisoning; Oligopeptides; Peritoneal Dialysis; Phalloidine; Radioimmunoassay; Time Factors

The serum of patients suffering from Amanita phalloides poisoning was analysed in order to determine whether amanitines, which are the principal toxins of this fungus, were still present in the blood at the time of hospitalisation. In addition, the authors measured the concentrations of amanitines in the blood of dogs at different intervals after the ingestion of a fatal dose of Amanita phalloides. Amanitines were detected in the serum of 9 patients out of 16. This discovery, together with the finding that, in the dog, very low concentrations of amanitines in the blood are associated with fatal cellular lesions, suggests the need for very prompt action in order to eliminate these toxins from the blood as soon as the diagnosis of poisoning is suspected.

Topics: Amanita; Amanitins; Animals; Dogs; Humans; Liver; Mushroom Poisoning; Necrosis

Topics: Amanitins; Animals; Cell Nucleus; Dogs; Gastric Mucosa; Humans; Intestinal Mucosa; Kidney Tubules, Proximal; Liver; Mice; Mushroom Poisoning; Rats; RNA; RNA Polymerase II

The protective action of dibenzothioline and silymarin in the acute intoxication by phalloidin and alpha-amanitin has been studied on the basis of their ability to attenuate changes in dry mass distribution and class-pattern of the hepatocytes, as evaluated by microinterferometry. Protective agents were given to male rats 30 min before toxin, and the animals were sacrificed 3.0 h later. Both dibenzothioline and silymarin markedly counteract the toxic action of phalloidin and alpha-amanitin on the hepatocyte population, as revealed by a substantial prevention (a) of the striking displacement of hepatocytes in the intervals among the classes as regards phalloidin poisoning, and (b) of the number decrease of hepatocyte classes due to disappearance of the heaviest ones, of the shift of hepatocytes to the lighter classes, of the appearance of very light cells, of the displacement of hepatocytes into the class intervals and of the decrease in nuclear dry mass as regards alpha-amanitin. It is suggested that dibenzothioline and silymarin exert their protective action by a non-specific stabilization of the cell membrane.

Topics: Amanitins; Amino Acids, Sulfur; Animals; Cell Membrane; Flavonoids; Liver; Male; Mushroom Poisoning; Oligopeptides; Phalloidine; Pyridines; Rats; Silymarin

Agents with antagonistic effects against phalloidin or alpha-amanitin were tested in mice against lethal doses of an extract from the whole mushroom Amanita phalloides. The following categories of agents reduced lethality after the extract. First, agents protecting only against phalloidin such as rifampicin, phenylbutazone and antamanide. Second, silymarin and prednisolone which display both antiamatoxic and marked (silymarin) or moderate (prednisolone) anti-phallotoxic acitivty. Thioctic acid displayed some activity when tested against mid-lethal doses of the extract. Cytochrome c, a chemical with curative potencies against alpha-amanitin did not reduce the lethality of the exact. All of the effective agents acted only when applied prior to the poisoning. The pattern or protective activity would indicate that in mice death after single doses of Amanita phalloides may follow a qualitatively particular couse which is difficult to ascribe to phallo- or amatoxic effects alone.

Topics: Agaricales; Amanita; Amanitins; Animals; Antidotes; Carbon Tetrachloride; Cytochrome c Group; Female; Mice; Mushroom Poisoning; Peptides, Cyclic; Phalloidine; Phenylbutazone; Plant Extracts; Prednisolone; Rifampin; Silymarin; Thioctic Acid

Poisonous species of fungi in Germany are very few. Dangerous is the ingestion of raw, spoiled or poisonous mushrooms. There exist no reliable tests to determine whether a mushroom is safe except by expert examination and identification of the mushroom. In clinical practice the classification of mushroom poisoning is possible in muscarine-syndrome, gastroenteritic syndrome and in two-phase-syndrome. 90-95% of lethal mushroom poisonings are due to ingestion of Amanita phalloides. In severe cases extensive hepatic necrosis occurs, characterized by profound abnormalities in liver function caused by hepatic coma. In deep coma mortality rates amount to 70% or more. A new therapeutic measure (coated charcoal hemoperfusion)-first applied in liver failure by Chang (1972) and Williams (1973)-has been performed in 3 patients with severe poisoning after ingestion of Amanita phalloides (each patient had eaten at least 7-10 fungi Amanita phalloides). Two of the patients survived.

Topics: Adult; Amanitins; Charcoal; Female; Hepatic Encephalopathy; Humans; Male; Methods; Middle Aged; Mushroom Poisoning; Renal Dialysis

Topics: Adult; Agaricales; Aged; Amanita; Amanitins; Chemical and Drug Induced Liver Injury; Female; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Mushroom Poisoning; Oligopeptides; Phalloidine

Topics: Amanita; Amanitins; Humans; Mushroom Poisoning

Topics: Agaricales; Amanita; Amanitins; Humans; Male; Mushroom Poisoning; Oligopeptides; Phalloidine

Topics: Agaricales; Amanitins; Animals; Islands; Islets of Langerhans; Mushroom Poisoning; Pancreas