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Toxic metabolites of Amanita pantherina, A. cothurnata, A. muscaria and other Amanita species.

Forty-seven specimens representing 35 species or varieties of Amanita were examined for the presence of ibotenic acid, muscimol, stizolobic acid, stizolobinic acid, aminohexadienoic acid and chlorocrotylglycine. In addition, crude extracts of A. muscaria were examined chromatographically for the presence of methyltetrahydrocarboline carboxylic acid (MTC). Ibotenic acid and muscimol were found in clearly detectable concentrations in extracts of A. cothurnata, all specimens of A. muscaria, all specimens of A. pantherina and in lower concentrations in A. gemmata. Stizolobic acid and stizobinic acid were found in detectable concentrations in one variety of A. muscaria, in all specimens of A. pantherina and in trace levels after additional purification of the extracts in A. gemmata and in the remaining specimens of A. muscaria. Aminohexadienoic acid and chlorocrotylglycine were detected only in crude extracts of A. smithiana. MTC could not be detected in crude extracts of A. muscaria. Crystalline ibotenic acid (820 mg) was isolated from 17 kg of a specimen of A. pantherina collected in western Washington State.

Agaricales

Unique amanitin resistance of RNA synthesis in isolated nuclei from Amanita species accumulating amanitins.

In order to understand the basis upon which amanitin-accumulating species of Amanita are able to develop in the presence of these specific inhibitors of RNA synthesis, the in vitro RNA synthesizing activities of nuclei isolated from amanitin-accumulating species. Amanita hygroscopica (culture, derived from amanitin-accumulating carpophore) and A. suballiacea (carpophore), and from the non-accumulating species A. solitaria (culture) and A. brunnescens (carpophore) were tested for their sensitivities to alpha-amanitin inhibition. The nuclear RNA synthesizing activities obtained from both carpophores and cultures of non-accumulating organisms displayed significant sensitivities to alpha-amanitin, whereas those obtained from accumulating organisms displayed remarkable resistance to alpha-amanitin. The observed relationship between levels of amanitins in carpophores and resistance of the RNA synthesizing activities to inhibition by alpha-amanitin supports the hypothesis that amanitins may function as regulators of mRNA transcription in Amanita species.

Agaricales

Comparative studies on orthotopic liver allotransplantation in pigs after intoxication with extracts from amanita phalloides and after a long-term preservation of transplants.

The paper deals with results obtained in two experimental groups of pigs after orthotopic liver allotransplantation. The first group involved recipients intoxicated with a lethal dose of extracts from Amanita phalloides before the transplantation. The other was not given toxins from Amanita phalloides; the transplanted livers, however, were preserved for a long time. The authors briefly describe the surgical procedure, method of liver preservation and application of toxins from Amanita phalloides. Results of orthotopic allotransplantations are discussed with regard to the survival period, death causes, clinical findings, and some biochemical values.

Amanita

[Glucose tolerance and insulin sensitivity of rats poisoned with amanita-phalloidines].

The effect Amanita phalloides on glucose tolerance and insuline sensitivity was studied. Amanita phalloides toxins were injected to albino male rats intraperitoneally in a dose of DL50. Amanita phalloides proved to cause disturbance of glucose tolerance, increased tissue glucose utilization, and enhanced the organism insuline sensitivity. The mentioned effects result from a decrease of insuline-inactivating capacity of the liver and from enhanced function of the insuline apparatus of the pancreas.

Amanita

Antagonistic effects against single lethal doses of Amanita phalloides.

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.

Agaricales

Poisoning with brown fly agaric, Amanita regalis.

Three patients ate different amounts of a common northern mushroom, brown fly agaric, Amanita regalis. All of them believed they had eaten delicious parasol mushrooms, Macrolepiota procera. The symptoms of poisoning began 1--2 hours after ingestion of the mushrooms. All the patients had marked gastrointestinal symptoms: nausea and heavy vomiting. Two had central nervous system manifestations and cholinergic symptoms: hallucinations, confusion, or loss of consciousness as well as copious salivation, or sweating. All patients recovered within 4--24 hours without any damage to liver, kidneys or central nervous system. It seems that cooking the mushrooms does not completely neutralize the toxic agents of Amanita regalis. The analysis of fried mushrooms shows that it may be possible to identify mushrooms reliably from the remains of a meal.

Adult

Determination of alpha-, beta-, and gamma-amanitin by high performance thin-layer chromatography in Amanita phalloides (Vaill. ex Fr.) secr. from various origin.

A fast, sensitive high performance thin-layer chromatographic method for the determination of alpha-, beta-, and gamma-amanitin in crude, methanolic extracts of Amanita phalloides is described. The limit of detection is 50 ng of each amanitin. With this method amanitin was determined in 24 pooled samples of Amanita phalloides, collected between 1970 and 1977 in Germany and Switzerland. The total amanitin content varied between 2010 and 7300 mg/kg dry weight and the average value was 4430 mg/kg of which 43% was alpha-amanitin, 49% beta-amanitin and 8% gamma-amanitin. The origin of the fungi hardly influenced their amanitin content: in samples collected during the same year at different sites it fluctuated within a factor of 1.7. The amanitin content of samples from the same site, but collected in different years, maximally varied within a factor of 3.7. The partial decomposition of amanitins during prolonged storage of the lyophilized samples undoubtedly contributed to this variation. Phalloidin, which was determined by conventional thin-layer-chromatography, could not be detected in a sample from 1970, whereas its concentration in material collected during 1977 amounted to 2400 mg/kg dry weight. The toxicity of the samples (LD50 of lyophilized defatted methanolic extracts intravenously for mice) varied within a factor of 2.5.

Agaricales

Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous Amanita mushrooms.

This review gives a comprehensive account of the molecular toxicology of the bicyclic peptides obtained from the poisonous mushrooms of the genus Amanita. The discussion of the biochemical events will be preceded by a consideration of the chemistry of the toxic peptides. The structural features essential for biological activities of both the amatoxins and the phallotoxins will be discussed, also including the most important analytical data. Similar consideration will be given to antamanide, a cyclic peptide, which counteracts phalloidin. In addition, the phallolysins, three cytolytic proteins from Amanita phalloides will be discussed. The report on the biological activity of the amatoxins will deal with the sensitivity of the different RNA-polymerases towards the toxins and with their action on various cell types. Consideration will also be given to systems in which alpha-amanitin was used and can be used as a molecular tool; in the past, many investigators used the inhibitor in molecular biology, genetics, and even in physiological research. As for the phallotoxins, discussion of the affinity of these toxins for actin is provied. Further discussion attempts to understand the course of intoxication by filling in the gap between the first molecular event, formation of microfilaments, and the various lesions in hepatocytes during the intoxication.

Agaricales

[Electron miscoscopy studies of liver tissue in patients with amanita phalloides poisoning].

Electron microscopic findings of the liver are being described found in 4 patients aged from 12 months to 26 years after poisoning with Amanita phalloides. Marked alterations were seen in nuclei, in the endoplasmic reticulum, and in mitochondria. Morphologic criteria of cholestasis were observed in one patient. Extreme cellular edema was found in two patients. Since our findings differ considerably in several points from those patients with Amanita phalloides poisoning previously reported, one may suppose, that e.g. age, sex, preexisting damage and liver function might be highly important for the extent and form of resulting liver damage.

Adolescent

[Amanita phalloides poisoning in Austria (author's transl)].

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.

Adult

[Fetal damage due to mushroom poisoning with amanita phalloides during the first trimester of pregnancy (author's transl)].

A 25-year old para II suffered of mushroom poisoning by amanita phalloides at 9 weeks gestation. When the life threatening maternal illness was overcome a therapeutic abortion was carried out at 12 weeks gestation. Prostaglandin F2 alpha was injected retro-amniotically. The damage to the fetus by the toxins of amanita phalloides is described and discussed.

Abortion, Therapeutic

Diagnosis and treatment of Amanita phalloides-type mushroom poisoning: use of thioctic acid.

The number of cases of mushroom poisoning is increasing as a result of the increasing popularity of "wild" mushroom consumption. Amanitin and phalloidin cytotoxins found in some Amanita and Galerina species produce the most severe and frequent life-threatening symptoms of Amanita phalloidestype poisoning. Delay in onset of symptoms, individual susceptibility variation and lack of rapid and reliable identification have contributed to the significant morbidity and mortality of this type of poisoning.A rapid chromatographic assay for identifying the potent cytotoxins and apparently successful management using thioctic acid of two cases of A. phalloides-type mushroom poisoning are reported. All known cases of A. phalloides-type mushroom poisoning treated with thioctic acid in the United States are summarized.

Adolescent

[Continuous EEG monitoring and clinical chemical findings in poisoning from Death cap (Amanita phalloides) (author's transl)].

The changes in the EEG were put in relation to the clinical course and liver function tests in 3 cases of acute poisoning by Amanita phalloides. Within discrete disturbances of liver function, distinct paroxysmal changes and increased interspersion of epsilon waves in the EEG are already found on the second day after taking the fungi. The liver dystrophy developing in the later course, recognisable by Quick values below 2%, at first only produces a small increase in the EEG changes. On the 5th or 6th day, severe general changes in the EEG appear along with symptoms of confusion to delirium. At this time, no further deterioration of the laboratory findings were demonstrable, but on the contrary we already even found a distinct improvement in the liver function. With further continuous increase in the clotting factors, the EEG becomes increasing slower in the next 4 days and after surviving this stage, improves very quickly thereafter. Our findings show that in poisoning with Amanita phalloides, EEG changes may become manifest even before the appearance of psycho-pathological changes and do not correlate directly with the tangible technical liver function tests of the laboratory.

Adult

[The determination of amanitines in the serum of patients poisoned by amanita phalloides (author's transl)].

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.

Amanita

Experience of treatment in the Amanita phalloides poisoning (clinical and experimental observations).

Intensive care was applied in 13 patients with acute liver insufficiency and different degrees of metabolic encephalopathy due to the ingestion of Amanita phalloides. Twelve of them were subjected to hepatic assist with E.T., in three cases this measure was repeated. Ten recoveries were obtained, which denote, on the basis of the necrosis enzymes and the hepatic histo-pathological aspects from bioptic samplings, the use of the E.T. method, when applied within the first 72 hours. In pigs poisoned with Amanita phalloides, the clinico-biochemical pattern and the histopathological findings are comparable to the observations in man. Electron microscopy demonstrates peculiar lesion in the cytoplasm. The anatomo-pathological findings in the three dead patients show a liver necrosis over the 90% and the presence of cerebral edema.

Adolescent

Amanita mushroom poisoning with recovery from coma: a case report.

The incidence of Amanita mushroom poisoning seems to be increasing in the United States. Its neurological aspects contribute importantly to morbidity and mortality. In reported series, mortality has ranged from 50 to 90%, and survival following the appearance of coma was exceptional. The cause of nervous system involvement was uncertain. In the patient presented here, clinical and electroencephalographic observations were consistent with severe hepatic encephalopathy and correlated closely with liver function abnormalities. Despite the development of coma, full recovery followed the use of thioctic acid, an experimental therapeutic agent.

Amanita