Ground Glass-Like Inclusions: Associated with Liver Toxicity.

OBJECTIVE: The etiology of ground glass-like inclusions is heterogenous and the pathology has been described in various conditions including HBV infection, Lafora's disease, fibrinogen storage disease, type IV glycogenosis, and alcohol reversion therapy. Similar ground glass-like inclusions are also associated with immunosuppressed conditions and multiple medications, for which the clinical significance is still unclear. Additional cases, some with previously unreported unique etiologies, and their follow-up were described in this study. MATERIALS AND METHODS: Eleven cases were examined between 2008 and 2019 for this study. The clinical data and histologic slides were reviewed. All of the cases were negative for Hepatitis B virus. None of the patients declared alcohol intake or a history of epilepsy. RESULTS: Liver histology showed mild lobular inflammation in most of the cases (72%). Ground glass-like hepatocytes were distributed in the patchy-panlobular, periportal, and centrizonal pattern at 55%, 27%, and 18%, respectively. Clinical history revealed medication use in nine (82%) patients including NSAIDs, steroids, and chemotherapy. Ground glass-like inclusions were related to herbal toxicity in two of the patients. Liver function tests were elevated in all of the cases. Follow-up data revealed four patients with malignancy who died of their cancer. Seven patients showed resolution of elevated liver enzymes with a median follow-up period of 37 months (range 7-132 months). CONCLUSIONS: Medication is the most relevant etiology for the development of these inclusions. Ground glass-like inclusions may also seen in herbal toxicity. Transplantation was not an etiologic factor in our patients. Most of the patients displayed an indolent course with resolution of the elevated transaminases.

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

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

Chaga mushroom-induced oxalate nephropathy.

Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms.

[Acute hepatic failure after ingestion of mushrooms]. / Akutes Leberversagen nach Pilzingestion.

This report is about a married couple who were admitted to hospital suffering from gastrointestinal complaints after eating mushrooms. With the suspicion of poisoning with Amanita phalloides treatment started with elimination of the toxins, symptomatic therapy and specific therapy with silibinin. After quantitative determination of the Amanita toxins the patients were immediately transferred to a university hospital.Poisoning by the death cap mushroom is responsible for acute hepatic and often also renal failure and is accompanied by a high mortality. Clinical symptoms follow a three-phase course with gastrointestinal complaints, an asymptomatic interval and finally the hepatorenal phase. Even in suspected cases of intoxication, treatment should be started by antidote therapy with silibinin.

Legalon® SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning.

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.

Acute and subchronic oral toxicity of Coriolus versicolor standardized water extract in Sprague-Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Coriolus versicolor, which is known as Yun Zhi, is one of the commonly used Chinese medicinal herbs. Recent studies have demonstrated its antitumor activities on cancer cells which led to its widespread use in cancer patient. However, little toxicological information is available regarding its safety. The present study evaluated the potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats. MATERIALS AND METHODS: In acute toxicity study, Coriolus versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6 males, 6 females) at single doses of varying concentrations 1250, 2500 and 5000 mg/kg. In subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28 days to male and female SD rats respectively. General behavior, adverse effects and mortality were determined throughout the experimental period. Haematological and biochemical parameters, relative organ weights and histopathological were evaluated at the end of the experiment. RESULTS: There were no mortality and signs of toxicity in acute and subchronic toxicity studies. In the single dose acute toxicity and repeated dose 28-day subchronic toxicity studies, there were no significant difference in body weight, relative organ weight, haematological parameters, clinical chemistry, gross pathology and histopathology between treatment and control groups. CONCLUSIONS: Coriolus versicolor water extract did not cause remarkable adverse effect in SD rats. The oral lethal dose of Coriolus versicolor water extract is more than 5000 mg/kg and no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is 5000 mg/kg per day for 28 days.

Reversible pancytopenia following the consumption of decoction of Ganoderma neojaponicum Imazeki.

The Ganoderma species are mushrooms used for herbal medicinal purposes in northeast Asia. Two cases of simultaneous reversible pancytopenia following the consumption of decoction of Ganoderma neojaponicum Imazeki are presented. Other than decoction of G. neojaponicum Imazeki no cause of pancytopenia could be identified. The patients recovered fully after conservative treatment. People who consume herbal medicines are often not aware of their side effects. Patients should be knowledgeable regarding the possible side effects of Ganoderma prior to its consumption.

Revisiting Wasson's Soma: exploring the effects of preparation on the chemistry of Amanita muscaria.

In 1968 R. Gordon Wasson first proposed his groundbreaking theory identifying Soma, the hallucinogenic sacrament of the Vedas, as the Amanita muscaria mushroom. While Wasson's theory has garnered acclaim, it is not without its faults. One omission in Wasson's theory is his failure to explain how pressing and filtering Soma, as described in the Rig Veda, supports his theory of Soma's identity. Several critics have reasoned that such preparation should be unnecessary if equivalent results can be obtained by consuming the raw plant, as is done with other psychoactive mushrooms. In order to address these specific criticisms over 600 anecdotal accounts of Amanita muscaria inebriation were collected and analyzed to determine the impact of preparation on Amanita muscaria's effects. The findings of this study demonstrated that the effects of Amanita muscaria were related to the type of preparation employed, and that its toxic effects were considerably reduced by preparations that paralleled those described for Soma in the Rig Veda. While unlikely to end debate over the identity of Soma, this study's findings help to solidify the foundation of Wasson's theory, and also to demonstrate the importance of preparation in understanding and uncovering the true identity of Soma.

[Mushroom poisonings: syndromic diagnosis and treatment]. / Pilzvergiftungen: Toxidrome, Diagnose und Therapie.

The major syndromes of mushroom poisoning can be divided by presentation timing: Early syndromes (symptom onset <6 hrs after ingestion) have little probability to cause organ damage. Epigastric pain, nausea, vomiting and diarrhea occur in most cases and treatment includes initial gastrointestinal decontamination with oral activated charcoal and fluid rehydration. In addition, an acute gastrointestinal syndrome can be combined with cholinergic toxicity, epileptiformic response or immuno-hemolytic anemia. Neurotoxic Syndromes may present as dysphoria, delirium, hallucinations or disulfiram-like reactions. Treatment is entirely supportive and if performed in hospital, the prognosis is good. Late syndromes (symptom onset >6 hrs after ingestion) are life-threatening due to liver- and renal failure. Patients who are jaundiced after an acute gastrointestinal episode, are suspected to be poisoned with Amatoxins. Patients with flank pain, hematuria, polyuria or oliguria in the absence of jaundice are suspected to have an intoxication with Cortinarius mushrooms. In both cases an intensive care management is indicated.

The toxicology of Amanita phalloides.

This paper examines the biology and medical consequences of ingesting the potential lethal poisonous mushroom, Amanita phalloides, the Death Cap. The organism is a fungus, its structure, distribution and toxic components are described. Symptoms of human poisoning by Am. phalloides are described, following the order of Homeopathic Repertories.

Hepatotoxicity of botanicals.

OBJECTIVE: Hepatic impairment resulting from the use of conventional drugs is widely acknowledged, but there is less awareness of the potential hepatotoxicity of herbal preparations and other botanicals, many of which are believed to be harmless and are commonly used for self-medication without supervision. The aim of this paper is to examine the evidence for hepatotoxicity of botanicals and draw conclusions regarding their pathology, safety and applications. DESIGN: Current literature on the hepatotoxicity of herbal drugs and other botanicals is reviewed. The aetiology, clinical picture and treatment of mushroom (Amanita) poisoning are described. RESULTS: Hepatotoxic effects have been reported for some Chinese herbal medicines (such as Jin Bu Huan, Ma-Huang and Sho-saiko-to), pyrrolizidine alkaloid-containing plants, germander (Teucrium chamaedrys), chaparral (Larrea tridentata), Atractylis gummifera, Callilepsis laureola, and others. The frequency with which botanicals cause hepatic damage is unclear. There is a lack of controlled treatment trials and the few studies published to date do not clarify the incidence of adverse effects. Many plant products do not seem to lead to toxic effects in everyone taking them, and they commonly lack a strict dose-dependency. For some products, such as Sho-saiko-to, the picture is confused further by demonstrations of hepatoprotective properties for some components. Mushroom poisoning is mostly due to the accidental consumption of Amanita species. Treatment with silymarin, thioctic acid, penicillin and liver transplantation have been shown to be effective but require early diagnosis. CONCLUSIONS: Severe liver injury, including acute and chronic abnormalities and even cirrhotic transformation and liver failure, has been described after the ingestion of a wide range of herbal products and other botanical ingredients, such as mushrooms. It is concluded that in certain situations herbal products may be just as harmful as conventional drugs.

Amanita phalloides, a potentially lethal mushroom: its clinical presentation and therapeutic options.

Mushroom poisoning with Amanita phalloides, a rare phenomenon in everyday clinical practice in the Netherlands, must be recognized early in view of its potential morbidity and mortality. In this article 2 cases of amanita intoxication are presented and the pharmacological basis and clinical manifestations discussed. Furthermore, the rationale of various treatment modalities, including the role of liver transplantation, is outlined.

Effects of pre-treatment with aflatoxin on a second aflatoxin treatment in guinea pigs.

Two-hundred guinea pigs, weighing approximately 500 grams each, were placed in 8 groups, 4 of which received 20 micrograms/kg/day of partially purified aflatoxin for 7 days, followed by a 7 day recovery period. Paired groups then received 0, 20, 35 or 50 micrograms/kg/day of partially purified aflatoxin for 21 days. Animals were sacrificed periodically from all groups and blood was drawn for chemical and immunologic analysis. Weight gains were recorded and histopathologic studies were done on all animals. Pretreatment did not protect guinea pigs from a second exposure, and in fact enhanced mortality and liver toxicity as determined by histopathology. Serum chemistries and immunologic parameters of guinea pigs dosed twice were less conclusive, as neither high nor low doses differed from guinea pigs treated once. Glycocholic acid concentrations were more sensitive than traditional enzymes (aspartate and alanine amino transferase, alkaline phosphatase) for indicating hepatotoxicity.

Common toxic plant ingestions.

This article focuses on some of the more common dangerous plant and mushroom ingestions, discussing toxic components, early symptoms, and treatment. Among the plants considered are oleander, foxglove, hemlock, dieffenbachia, and Amanita phalloides. Details concerning recognition of toxic species are intentionally omitted in an effort to avoid potentially dangerous errors in identification.