Hepatotoxicidad por Amanita lilloi, reporte de primeros casos / Amanita lilloi hepatotoxicity, first cases report

Se presentan dos casos clínicos de intoxicación por A. lilloi, hongos silvestres, que fueron recolectados por quienes los consumieron. Ambas pacientes desarrollaron sintomatología digestiva y evolucionaron a la falla hepática. La consulta tardía retrasó el diagnóstico y el tratamiento, pero igualmente la evolución de ambas pacientes fue favorable.

Two clinical cases of poisoning A. lilloi, wild mushrooms, which were collected by those who consumed themdebe, are presented. Both patients developed gastrointestinal symptoms and progressed to liver failure. The late consultation delayed diagnosis and treatment, but nevertheless the evolution of both patients was favorable.

MicroRNA-24 modulates aflatoxin B1-related hepatocellular carcinoma prognosis and tumorigenesis.

MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66-8.47) and overall survival (HR = 3.58, 95% CI = 2.34-5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.

Mycotoxins and human health.

Mycotoxins have been investigated in relation to a wide range of adverse human health effects, but the evidence for all but a small number of associations is limited. Thus, the full impact on human health of the widespread exposure to mycotoxins remains to be defined. The main exception is for aflatoxins; epidemiological, experimental, and mechanistic studies have contributed to establishing aflatoxins as a cause of human liver cancer, with a particularly elevated risk in people chronically infected with hepatitis B virus. In addition, acute aflatoxicosis after exposure to high dietary toxin levels has been demonstrated. The impairment of child growth by aflatoxin exposure early in life remains an important subject of study. More information is also required on the potential immune effects of aflatoxins, especially in vulnerable populations. For fumonisins, studies indicate a possible role in oesophageal cancer and in neural tube defects, although no definitive conclusions can be drawn at present. For deoxynivalenol and other trichothecenes, exposure has been linked to acute poisoning outbreaks in large numbers of subjects. For ochratoxin A and zearalenone, the human health effects remain undefined. The limited tools available to accurately assess human exposure to mycotoxins and the relative paucity of epidemiological studies need to be addressed if the full extent of the adverse effects of these common dietary contaminants is to be understood and adequate public health measures taken. In this respect, newly established biomarkers of exposure at the individual level are proving valuable in improving exposure assessment in epidemiological studies.

Risk assessment and risk management of mycotoxins.

Risk assessment is the process of quantifying the magnitude and exposure, or probability, of a harmful effect to individuals or populations from certain agents or activities. Here, we summarize the four steps of risk assessment: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Risk assessments using these principles have been conducted on the major mycotoxins (aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, and zearalenone) by various regulatory agencies for the purpose of setting food safety guidelines. We critically evaluate the impact of these risk assessment parameters on the estimated global burden of the associated diseases as well as the impact of regulatory measures on food supply and international trade. Apart from the well-established risk posed by aflatoxins, many uncertainties still exist about risk assessments for the other major mycotoxins, often reflecting a lack of epidemiological data. Differences exist in the risk management strategies and in the ways different governments impose regulations and technologies to reduce levels of mycotoxins in the food-chain. Regulatory measures have very little impact on remote rural and subsistence farming communities in developing countries, in contrast to developed countries, where regulations are strictly enforced to reduce and/or remove mycotoxin contamination. However, in the absence of the relevant technologies or the necessary infrastructure, we highlight simple intervention practices to reduce mycotoxin contamination in the field and/or prevent mycotoxin formation during storage.

Toxicology of mycotoxins.

Humans are exposed to mycotoxins via ingestion, contact and inhalation. This must have occurred throughout human history and led to severe outbreaks. Potential diseases range from akakabio-byo to stachybotryotoxicosis and cancer. The known molecular bases of toxicology run the gamut of 23 compounds, from aflatoxins (AFs) to zearalenone, ochratoxin A and deoxynivalenol. Ergotism is one of the oldest recognized mycotoxicosis, although mycotoxin science only commenced in the 1960s with the discovery of AFs in turkey feed. AFs are carcinogenic. Some others are suspected carcinogens. The effects of mycotoxins are acute or chronic in nature. Mycotoxins are well known in the scientific community, although they have a low profile in the general population. An incongruous situation occurs in United States where mycotoxins from "moldy homes" are considered to be a significant problem, although there is a general debate about seriousness. This contrasts with the thousands of deaths from mycotoxins that occur, even now, in the technologically less developed countries (e.g., Indonesia, China, and Africa). Mycotoxins are more toxic than pesticides. Studies are moving from whole animal work to investigating the biochemical mechanisms in isolated cells, and the mechanisms of toxicity at the molecular level are being elucidated. The stereochemical nature of AFs has been shown to be important. In addition, the effect of multiple mycotoxins is being increasingly investigated, which will more accurately represent the situation in nature. It is anticipated that more fungal metabolites will be recognized as dangerous toxins and permitted statutory levels will decrease in the future.

Micobiota e micotoxinas em amostras de arroz coletadas durante o sistema estacionário de secagem e armazenamento / Mycobiota and mycotoxins in rice samples collected during the stationary drying and storage system

Considerando as perdas qualitativas e quantitativas no período pós-colheita de grãos, neste trabalho foram avaliadas a contaminação fúngica e as micotoxinas em arroz com casca, durante o sistema estacionário de secagem e armazenamento. As amostras foram coletadas em intervalos de 60 dias durante o armazenamento, em duas alturas do silo-secador. A amostra inicial apresentou 5,4x10(4)UFC g-1, sendo que a contagem aumentou significativamente durante a secagem e o armazenamento, chegando a 10(5)UFC g-1. A contaminação fúngica diferiu no interior do silo-secador, com maior contaminação na porção superior do silo. Os gêneros predominantes foram Aspergillus e Penicillium, com maior ocorrência de A. flavus (26,3 por cento) e P. commune (19,1 por cento). Quatro isolados de A. flavus produziram aflatoxina B1, mas não foram detectadas micotoxinas nas amostras.

Considering the qualitative and quantitative losses in post-harvest of grain, in this research was evaluated fungi and mycotoxins contamination in whole rice (Oryza sativa L.) during the stationary drying and storage system. Samples were collected in a period of sixty days in two heights of the warehouse during storage. The initial sample presented 5.4x10(4)CFU g-1; the contamination increased significantly during drying and storage, up to 10(5)CFU g-1. Fungi contamination was different inside the warehouse with higher contamination in the upper portion. The more abundant fungi genera were Aspergillus and Penicillium, A. flavus (26.3 percent) and P. commune (19.1 percent) which presented higher incidence. Aflatoxin B1 was produced by four A. flavus isolates, but mycotoxins were not detected in the samples.

[Medical relevance of mycotoxins]. / Medizinische Relevanz der Mykotoxine.

There are many mycotoxins with different chemical structures and biological activities. They are present in many food items of vegetable and animal origin as well as in the air. Consequently the exposure of humans to these agents is rather common. In some particular instances the dosage taken up by the body may be considerable. The various biological effects of mycotoxins such as organ toxicity, mutagenicity, carcinogenicity, teratogenicity and modulation of the immune system are well documented by in vitro and animal experiments. Furthermore, cases of intoxication by mycotoxins are well known in veterinary medicine. However, the relevance of mycotoxins in human medicine remains largely underestimated, because material from patients with characteristic symptoms is rarely tested for mycotoxins.

[Are mycotoxins in food a health hazard?]. / Sind Mykotoxine in Lebensmitteln gefährlich?

The effects of mycotoxins are well known since antiquity. Modern trace analysis show the wide prevalence of mycotoxins in the food chain. Aflatoxins (AFB1, AFB2, AFG1, AFG2), trichothecenes (deoxynivalenol, T-2 Toxin, HT-2 Toxin), zearalenone, fumonisins (FB1, FB2) and ochratoxin A are the most important mycotoxins world wide. Foods of plant origin are normally contaminated more frequently and in higher concentrations than food of animal origin. The mean concentrations of mycotoxins analysed in European foods can be assed as low. This may be one reason why acute poisonings are rare incidences and why the limits of the tolerable daily intake (TDI) levels are exceeded only very seldom; however the population group "infant" exceed the preliminary TDI-level for trichothecenes. The consequences of a chronic intake of low amounts of mykotoxins is hardly to assess. A participation of the aflatoxins in the pathogenesis of primary liver cancer is considered as certain. Other coherence between the dietary intake of mycotoxins and specific clinical symptoms of man are not convincingly shown till now.

The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.

Mycotoxins of aspergilli: exposure and health effects.

Mycotoxins derived from Aspergilli can be encountered both in domestic and occupational environments, and the exposure may lead to severe health hazards. Several Aspergillus species are associated with mycotoxin production: A. ochraceus with ochratoxin A, A. fumigatus with fumitremorgins, gliotoxin and verrucologen, A. versicolor with sterigmatocystin, and A. flavus and A. parasiticus with aflatoxins. Sterigmatocystin may also be produced by A. flavus, A. nidulans, A. rugulosus, and A. unguis. Exposure to mycotoxin may occur via enteric, inhalation or direct contact to skin and mucosa. Acute and chronic disorders, irritation, systemic reactions and even cancer may develop after the exposure to these toxins. Mycotoxins act as immunosuppressants which may be in association with an increased prevalence of repeated infections found among the inhabitants of buildings with moisture problems.

Use of functional brain imaging in the evaluation of exposure to mycotoxins and toxins encountered in Desert Storm/Desert Shield.

In this retrospective analysis the authors compared brain scintigrams, performed using triple-head single-photon emission computed tomography (tripleSPECT), of subjects who were judged clinically impaired from exposure to toxins during the Desert Storm/Desert Shield military action, and of subjects exposed to mycotoxins, with those of normal controls. The scintigrams for both exposed groups exhibited similar patterns of abnormalities, which were consistent with neurotoxic impairment. The authors conclude that further study is needed to determine whether mycotoxin exposure may be a cause of abnormalities seen in tripleSPECT images.

Antioxidant nutrients and mycotoxins.

Mycotoxins are fungal secondary metabolites that are toxic to vertebrates produced by organisms that occur as plant pathogens, soilborne fungi, airborne fungi and aeroallergens. They are distributed worldwide and may be recovered from a wide range of substrates. Their presence in food and feeds, as the result of fungal diseases in crops, can present a danger to animal and human health. Many mycotoxins have also been shown to be phytotoxic and in some cases, such as with trichothecenes produced by the wheat head blight fungus Fusarium graminearum, mycotoxins may act as virulence factors. Several natural (vitamin, provitamins, carotenoids, chlorophyll and its derivatives, phenolics, and selenium) and synthetic (butylated hydroxyanisole and butylated hydroxytoluene) compounds with antioxidant properties seem to be potentially very efficacious in protecting against the toxic effects of mycotoxins. The protective properties of antioxidants are probably due to their ability to act as superoxide anion scavengers, thereby protecting cell membranes from mycotoxin-induced damage and in some cases, antioxidant vitamins may play a role in preventing mycotoxicosis. However, much less information is available from studies carried out on antioxidants and mycotoxins, such as OTA, FB(1), T-2 toxin, ZEN, and citrinin. No such studies have been performed on recently discovered toxins such as beauvericin, fusaproliferin, moniliformin, and fusaric acid. However, supplementation with antioxidant nutrients to prevent mycotoxicosis has been controversial. The case for the use of supplemental antioxidant vitamins at the present time needs further research.

Acute penitrem A and roquefortine poisoning in a dog.

Penitrem A and roquefortine poisonings were diagnosed in a Laborador retriever following garbage consumption. Clinical signs of mycotoxicosis included polypnea, tachycardia, and ataxia that quickly progressed to lateral recumbency and seizures. Removal of the mycotoxins from the stomach soon after ingestion allowed the dog to recover within 72-96 hours.

Contamination of food with mycotoxins and human health.

Mycotoxins are natural contaminants of cereals and other commodities throughout the world. They are produced by various strains of moulds, particularly in tropical countries. Due to significant trade of cereals, humans in temperate countries can also be exposed to mycotoxins. The most common route of exposure to mycotoxins is ingestion, but it may also involve dermal, respiratory, and parenteral routes, the last being associated with drug abuse. Apart from acute and chronic toxic effects on human health called mycotoxicosis, some mycotoxins are proved or suspected human carcinogens. This paper describes various human diseases caused by ergot, afflatoxin, ochratoxin A, 3-nitropropionic acid, trichothecene, zearalenone, and fumonisin. It also gives a quick review of human carcinogenicity evaluations of the international Agency for Research on Cancer and of regulatory limits of mycotoxin concentrations in various commodities.

Toxigenic fungi and mycotoxins.

Growth of commonly occurring filamentous fungi in foods may result in production of toxins known as mycotoxins, which can cause a variety of ill effects in humans, from allergic responses to immunosuppression and cancer. The most important mycotoxins are aflatoxins, ochratoxin A, fumonisins, trichothecenes and zearalenone. Aflatoxins are potent carcinogens and, in association with hepatitis B virus, are responsible for many thousands of human deaths per annum, mostly in non-industrialised tropical countries. Ochratoxin A is a probable carcinogen, and may cause urinary tract cancer and kidney damage in people from northern and eastern Europe. Fumonisins appear to be the cause of oesophageal cancer in southern Africa, parts of China and elsewhere. Trichothecenes are highly immunosuppressive and zearalenone causes oestrogenic effects in animals and man. Currently available records and statistics do not reflect the major role played by mycotoxins in mortality attributable to food-borne micro-organisms.

[Micromycetes, mycotoxins and human health]. / Mikromycety, mykotoxiny a zdraví cloveka.

Mycotoxins are toxic metabolites produced by certain toxigenic microscopic fungi (moulds) in and on foods. Consequently mycotoxin-containing foods have been found all over the world: Africa, Asia, North and South America, Australia and Europe. The extent of the problem is greater in some parts of the world than in others because their climatic conditions are more favourable for mould growth and thus synthesis of mycotoxins. These toxins have been associated with various diseases-mycotoxicoses in humans throughout the world (ergotism, alimentary toxic aleukia, aflatoxicosis, balkan nephropathy, yellow rice disease, oesophageal cancer etc.). Mycotoxins can enter the food chain by one of two major routes: direct contamination resulting from the use of a food components contaminated with mycotoxins and indirect contamination resulting from the growth of toxigenic fungi of the food. Investigations of mycotoxins in foodstuffs, in human urine and human milk were incorporated into the system of Environmental Health Monitoring in the Czech Republic. The risk of acute toxic effects of mycotoxins was usually considered to be minimal in the Czech Republic. The risk of later toxic effects (particularly carcinogenic risk) after very low single or repeated mycotoxin concentrations in foodstuffs is very important.

Pharmaceutically active secondary metabolites of microorganisms.

The antibiotics have been useful in our battles against infectious bacteria and fungi for over 50 years. However, many antibiotics are used commercially, or are potentially useful, in medicine for activities other than their antibiotic action. They are used as antitumor agents, immunosuppressive agents, hypocholesterolemic agents, enzyme inhibitors, antimigraine agents, and antiparasitic agents. A number of these products were first discovered as antibiotics which failed in their development as such, or as mycotoxins. In addition to the above alternative applications, new powerful antibiotics have been discovered and commercialized in recent years and others are in clinical testing at the moment. A few successful secondary metabolites appear to have no antibiotic activity. The recently increased development of resistance to older antibacterial and antifungal drugs is being met with the use or clinical testing of older, underutilized or previously nondeveloped narrow-spectrum antibacterial products as well as powerful semisynthetic antifungal agents.

Intoxicações em eqüinos no Brasil / Intoxications in horses in Brazil

Relatam-se algumas intoxicaçöes descritas em eqüídeos no Brasil. Dentre as intoxicaçöes por plantas, incluem-se: Senecio spp., Ateleia glazioviana, Crotalaria juncea, Equisetum spp., Pteridium aquilinum, Baccharis coridifolia, Senna occidentalis e Brachiara spp.. Mencionam-se, também, as micotoxicoses causadas por Fusarium moniliforme, Claviceps purpurea e aflatoxinas, e as intoxicaçöes por uréia, iodo, chumbo e inseticidas clorados.

[Fumonisins--mycotoxins produced by Fusarium moniliforme]. / Fumonizini--mikotoksini koje proizvodi Fusarium moniliforme.

Fumonisins are toxic metabolites of the fungus Fusarium moniliforme and several other Fusaria that commonly contaminate corn. Only recently discovered in 1988, these mycotoxins appear to be causative agents of several toxicoses in animals that result from ingestion of moldy corn and corn-based feeds. These include equine leukoencephalomalacia, porcine pulmonary oedema, nephrotoxicity, hepatotoxicity, hepatocarcinogenicity in laboratory animals. There is also evidence that suggests that F. moniliforme and fumonisins may also be responsible for oesophageal cancer in humans in certain areas of the world where moldy corn is frequently consumed. Fumonisins are structurally similar to sphingosine, and may exert their biological activity to block enzymes sphinganine- and sphingosine-N-acyl transferase involved in sphingolipid biosynthesis.

Determinación de aflatoxina M1 en leche / Detection of aflatoxin M1 in milk samples

La presencia de micotoxinas en productos lácteos se debe, por lo general, a la ingesta por parte del ganado lechero de alimentos contaminados con aflatoxina B1 (AFB1). La AFM1 es el principal metabolito hepático 4-hidroxilado de la AFB1 que se excreta por la leche. Es tan tóxica como la AFB1, aunque algunos autores han demostrado que no es tan mutagénica. Recientemente se han clasificado a las AFB1 y AFM1 como carcinógenos humanos de la clase 1 y 2B respectivamente y también se ha observado que la AFM1 tiene una alta actividad genotóxica. El objetivo de este trabajo es determinar por TLC (cromatografía en capa delgada) la presencia de AFM1 en 50 muestras de leche, recolectadas en los meses de otoño, tanto de origen comercial como provenientes de pequeños tambos, donde se ordeñan artesanalmente, para estimar los niveles de exposición a la AFM1 en la población. No se detectó la presencia de AFM1 en ninguna de las muestras estudiadas hasta este momento. Esto muestra que en esta época del año, donde las vacas lecheras se alimentan de pasto natural, no existe contaminación. Seguiremos estudiando muestras recolectadas en los meses de invierno para controlar que sucede cuando además reciben suplemento alimentario. La leche es el alimento básico consumido sobre todo por niños en etapa de crecimiento; por lo tanto, debe ser monitoreada de contaminantes, incluyendo AFM1, más aún en países como el nuestro donde los factores climáticos pueden favorecer la incidencia de la misma. En nuestro país hay muy escasos datos de incidencia de AFM1 en la leche fluida, leche en polvo y en otros derivados lácteos. La dificultad para realizar estudios toxicológicos en humanos con la ingesta de AFM1 y la dificultad para la detoxificación de micotoxinas de las dietas hacen de los programas de monitoreo la principal estrategia para disminuir el riesgo de exposición a estas micotoxinas, por eso creemos que más estudios deberían efectuarse para intensificar los conocimientos acerca de toda nuestra producción lechera