Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1.

Mycotoxins, such as aflatoxin B1 (AFB1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB1 (0.5-1.0 mg/kg) intravenously and hemoperfusion with a CS or Control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4 hours. The CS device removes AFB1 from circulation and significantly improves survival when initiated within 90 minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. Changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with CS could be a viable countermeasure against acute mycotoxin exposure.

Retrospective and Prospective Look at Aflatoxin Research and Development from a Practical Standpoint.

Among the array of structurally and toxicologically diverse mycotoxins, aflatoxins have attracted the most interest of scientific research due to their high toxicity and incidence in foods and feeds. Despite the undeniable progress made in various aspects related to aflatoxins, the ultimate goal consisting of reducing the associated public health risks worldwide is far from being reached due to multiplicity of social, political, economic, geographic, climatic, and development factors. However, a reasonable degree of health protection is attained in industrialized countries owing to their scientific, administrative, and financial capacities allowing them to use high-tech agricultural management systems. Less fortunate situations exist in equatorial and sub-equatorial developing countries mainly practicing traditional agriculture managed by smallholders for subsistence, and where the climate is suitable for mould growth and aflatoxin production. This situation worsens due to climatic change producing conditions increasingly suitable for aflatoxigenic mould growth and toxin production. Accordingly, it is difficult to harmonize the regulatory standards of aflatoxins worldwide, which prevents agri-foods of developing countries from accessing the markets of industrialized countries. To tackle the multi-faceted aflatoxin problem, actions should be taken collectively by the international community involving scientific research, technological and social development, environment protection, awareness promotion, etc. International cooperation should foster technology transfer and exchange of pertinent technical information. This review presents the main historical discoveries leading to our present knowledge on aflatoxins and the challenges that should be addressed presently and in the future at various levels to ensure higher health protection for everybody. In short, it aims to elucidate where we come from and where we should go in terms of aflatoxin research/development.

Mycotoxin: Its Impact on Gut Health and Microbiota.

The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria-xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and mycotoxicosis.

Mycotoxicoses in children.

Mycotoxicoses are acute and chronic poisonings caused by mould toxins called mycotoxins. Although acute mycotoxicoses, caused by high mycotoxin levels in food are rare nowadays, they need to be described in order to inform physicians and other health care workers about their symptoms. Children are more sensitive to mycotoxins because of their lower body mass, higher metabolic rate, and underdeveloped organ functions and detoxication mechanisms. Some mycotoxicoses appear only in children, and some are more pronounced in children than in adults. Acute mycotoxicoses in children are reported poorly, mostly because they occur in the tropical regions with poor healthcare coverage. In developed countries healthcare authorities are more concerned about child exposure to low levels of mycotoxins with immunotoxic, genotoxic or carcinogenic properties.

Dehydration as an effective treatment for brevetoxicosis in loggerhead sea turtles (Caretta caretta).

Harmful algal blooms are known to cause morbidity and mortality to a large number of marine and estuarine organisms worldwide, including fish and marine mammals, birds, and turtles. The effects of these algal blooms on marine organisms are due to the various toxins produced by the different algal species. In southwest Florida, frequent blooms of the dinoflagellate Karenia brevis, which produces neurotoxins known as brevetoxins, cause widespread fish kills and affect many marine animals. In 2005-2007, numerous sea turtles of several species underwent treatment for brevetoxicosis at the Sea Turtle Rehabilitation Hospital. In green sea turtles, Chelonia mydas, and Kemp's ridley sea turtles, Lepidochelys kempii, symptoms associated with brevetoxicosis were limited to neurologic signs, such as the inability to control the head (head bobbing) and nervous twitching. For these turtles, treatment involved removing the turtles from the environment containing the toxins and providing short-term supportive care. In loggerhead sea turtles, Caretta caretta, symptoms were more generalized; thus, a similar approach was unsuccessful, as was routine treatment for general toxicosis. Loggerhead sea turtles had more extreme neurologic symptoms including coma, and other symptoms that included generalized edema, conjunctival edema, and cloacal or penile prolapse. Treatment of brevetoxicosis in loggerhead sea turtles required a therapeutic regimen that initially included dehydration and systemic antihistamine treatment followed by supportive care.

Reduction of aflatoxin level in aflatoxin-induced rats by the activity of probiotic Lactobacillus casei strain Shirota.

AIMS: Aflatoxin B1 (AFB1 ) is considered as the most toxic food contaminant, and microorganisms, especially bacteria, have been studied for their potential to reduce the bioavailability of mycotoxins including aflatoxins. Therefore, this research investigated the efficacy of oral administration of Lactobacillus casei Shirota (LcS) in aflatoxin-induced rats. METHODS AND RESULTS: Sprague Dawley rats were divided into three groups of untreated control, the group induced with AFB1 only, and the group given probiotic in addition to AFB1. In the group induced with AFB1 only, food intake and body weight were reduced significantly. The liver and kidney enzymes were significantly enhanced in both groups induced with AFB1 , but they were lower in the group given LcS. AFB1 was detected from all serum samples except for untreated control group's samples. Blood serum level of AFB1 in the group induced with AFB1 only was significantly higher than the group which received probiotic as a treatment (P < 0·05), and there was no significant difference between the control group and the group treated with probiotic. CONCLUSIONS: LcS supplementation could improve the adverse effect of AFB1 induction on rats' body weight, plasma biochemical parameters and also could reduce the level of AFB1 in blood serum. SIGNIFICANCE AND IMPACT OF THE STUDY: This study's outcomes contribute to better understanding of the potential of probiotic to reduce the bioavailability ofAFB1 . Moreover, it can open an opportunity for future investigations to study the efficacy of oral supplementation of probiotic LcS in reducing aflatoxin level in human.

Costs and efficacy of public health interventions to reduce aflatoxin-induced human disease.

This study reviews available information on the economics and efficacy of aflatoxin risk-reduction interventions, and it provides an approach for analysis of the cost-effectiveness of public health interventions to reduce aflatoxin-induced human disease. Many strategies have been developed to reduce aflatoxin or its adverse effects in the body. However, a question that has been under-addressed is how likely these strategies will be adopted in the countries that need them most to improve public health. This study evaluates two aspects crucial to the adoption of new technologies and methods: the costs and the efficacy of different strategies. First, different aflatoxin risk-reduction strategies are described and categorized into pre-harvest, post-harvest, dietary, and clinical settings. Relevant data on the costs and efficacy of each strategy, in reducing either aflatoxin in food or its metabolites in the body are then compiled and discussed. In addition, we describe which crops are affected by each intervention, who is likely to pay for the control strategy, and who is likely to benefit. A framework is described for how to evaluate cost-effectiveness of strategies according to World Health Organization (WHO) standards. Finally, it is discussed which strategies are likely to be cost-effective and helpful under different conditions worldwide of regulations, local produce and soil ecology, and potential health emergencies.

The treatment of patients with mycotoxin-induced disease.

Twenty-eight incapacitated individuals (average 43 years old, 7 males, 21 females, range 12-70) exposed to molds and mycotoxins were studied and treated with a protocol of cleaning up or changing their environment to be mold free. Injections of the optimum dose of antigens were given as part of the treatment protocol as was oral and intravenous (i.v.) antioxidants; heat depuration (sauna); physical therapy with massage and exercise under environmentally controlled conditions; oxygen therapy at 4-8 L/min for 2 hours with a special wood-grade cellophane reservoir and a glass oxygen container. Many patients were sensitive to plastics; therefore, exposures to these were kept to a minimum. Autogenous lymphocytic factor was given as an immune modulator. Of 28 patients, 27 did well and returned to work. One patient improved but did not return to work during the period of study.

Molds, mycotoxins, and nutrition.

Many of the patients with mold and chemical exposure that come to Environmental Health Center - Dallas (EHC-D) show signs of impaired digestion. Improving their digestion improves their nutritional status and also improves their detoxification abilities. Mold and chemical exposure also affect the patient's short-term memory and executive function. This presents a challenge when it comes to teaching the patient how to improve their nutritional status and detoxification. At the EHC-D, we use several instructions methods that have resulted in the patient's grasping the concepts and then being able to implement the required changes.

Acute aflatoxicosis: case report.

The objective of this presentation is to document the salient clinical findings in a case of aflatoxicosis and to review the literature on the same so as to increase the index of suspicion, enhance early diagnosis and improve management. The case was a 17-year-old schoolboy presenting with vomiting, features of infection and gastrointestinal tract symptoms. Examination revealed a very ill looking pale patient with abdominal distension, tenderness and rectal bleeding and easy bruisability. Investigations showed abnormal liver function tests, pancytopenia and elevated serum levels of aflatoxins. Management consisted of supportive care including antibiotics and antifungal therapy, transfusion of red blood cells and fresh frozen plasma. His recovery was uneventful. The literature on human aflatoxicosis shows that the presentation may be acute, subacute and chronic. The degree of emanating clinical events also conforms to status of the aflatoxicosis. Overall, the features are protean and may masquerade many other forms of toxaemias. In conclusion, the diagnosis of aflatoxicosis takes cognisance of geographical location, past events, staple diet and clinical features to exclude other infections. Also required are high index of suspicion and importantly serum levels of aflatoxin. Treatment strategies involved use of antimicrobials and supporting the damaged multi-organs.

Tremorgenic mycotoxin intoxication with penitrem A and roquefortine in two dogs.

In this report, we describe the natural intoxication of 2 dogs that consumed moldy dairy products found in the household garbage and the procedures used to identify and quantify the tremorgenic mycotoxins, roquefortine and penitrem A, in the remaining portions of ingested materials. Following the ingestion of mycotoxins, the dogs of our report developed muscle tremors or seizures that resembled clinical signs of strychnine poisoning. Roquefortine was the predominant mycotoxin in a moldy cream cheese wrapper that was found among scattered garbage consumed by the first dog. Penitrem A was the only mycotoxin detected in discarded moldy macaroni and cheese that was consumed by the second dog. Treatment of dogs with tremorgenic mycotoxin intoxication involves supportive care. Close monitoring is important because the development of aspiration pneumonia is common and has been reported as the cause of death. Clinical signs of intoxication gradually resolve within 24 to 48 hours.

Tremorgenic mycotoxicosis in four dogs from a single household.

Mycotoxins are fungal metabolites that induce undesirable effects. The effects of these mycotoxins vary depending on the chemical structure of the toxin and degree of toxicity. Mycotoxins that induce muscle tremors, ataxia, and convulsions are termed tremorgenic mycotoxins. Our report documents the clinical course of 4 dogs from a single household that were simultaneously affected by tremorgenic mycotoxins. Diagnosis of tremorgenic mycotoxicosis was confirmed by stomach content analysis from 1 of the dogs. The mycotoxins identified were penitrem A and roquefortine, which are both produced by Penicillium spp. Treatment goals following tremorgenic mycotoxin ingestion include minimizing absorption, controlling tremors and seizures with methocarbamol and pentobarbital sodium administration, and providing supportive care. Two of the affected dogs required ventilatory support. With early aggressive treatment, prognosis is good and recovery is complete without sequelae. It is helpful for the clinician to be familiar with the typical clinical signs at the time of admission, treatment, and clinical course of dogs with tremorgenic mycotoxicosis.

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.

Mycotoxins.

The relevance of many mycotoxins to small animal health is difficult to assess, because available information has not been collated and reviewed. Only aflatoxins, penitrem A, and roquefortine have been confirmed in natural mycotoxicoses in pets. Effects of tricothecene mycotoxins, patulin, and penicillic acid on dogs and cats have only been studied experimentally and have not been confirmed in natural outbreaks. Although they make up only a small portion of the cases presented to veterinarians, mycotoxicoses often require special effort. Establishing an accurate diagnosis is crucial to minimize exposure and provide adequate treatment. In most cases, clinical examination, clinical pathologic testing, and analytical chemistry analysis of suspect feed are necessary to reach a diagnosis.

Diagnosis and management of suspected cases of bioterrorism: a pediatric perspective.

Since October 3, 2001, the Centers for Disease Control and Prevention and other organizations have been investigating potential bioterrorist-related anthrax cases. The pediatrician may be faced with complex issues related to diagnosis and treatment of illnesses caused by intentionally released biological agents. The agents that pose a major potential bioterrorist threat are reviewed by the clinical syndromes they produce: acute respiratory distress with fever, influenza-like illnesses, acute rash with fever, neurologic syndromes, and blistering syndromes. Specific and detailed diagnostic, treatment, and prophylaxis information is provided for anthrax, plague, tularemia, smallpox, botulism, viral hemorrhagic fevers, and other diseases. In cases of suspected bioterrorism, the pediatrician must be able to obtain diagnostic and treatment information efficiently and expeditiously. The system controlling the interaction between public and nonpublic health laboratories in suspected cases of bioterrorism is described. Finally, information regarding emergency contacts and links to educational resources is provided.

Nuevos casos de amanitismo en Chile / New cases of amanitism in Chile

Nueve personas padecieron de un severo micetismo en junio de 1999 por comer basidiomas de amanita phalloides (Vaill. ex Fr.) Secr. recolectadas en Linares (VII región). Dos de los pacientes fallecieron. Se hace referencia también a algunos de los hongos venenosos más comunes en Chile

Intoxicación alimentaria por hongos silvestres (micetismo) / Food poisoning by fungi (micetism)

En el planeta existe una gran variedad de setas, muchas de ellas tóxicas e incluso mortales. La intoxicación alimentaria por la ingestión de hongos (micetismo) es un problema muy difundido cuyo diagnóstico se confunde o pasa inadvertido. Se señalan los estados de la República en donde el mecetismo se presenta con mayor frecuencia, se alude a su cuadro clínico, diagnóstico y tratamiento

The distribution, diagnoses and estimated economic impact of plant poisonings and mycotoxicoses in South Africa.

Maps are provided showing the national and provincial distributions of many plant poisonings and mycotoxicoses in South Africa. The various poisonings are briefly described and criteria for their diagnoses are given. The annual mortalities of cattle from plant poisonings/mycotoxicoses in South Africa were calculated as c. 37 665 head with a current cash value of c. R57 627 450, and that of small stock as c. 264851 head with a value of c. R46 878 627. The annual total cost of plant poisonings/mycotoxicoses to the livestock industry of South Africa is conservatively estimated at R104 506 077. These figures do not include hidden losses such as diminished production, reproductive failure, the cost of not utilizing toxic pastures and the fall in price of infested land.

Intoxicación por callampas venenosas en la IX región: rol de amanita gemmata / Intoxication by poisoning mushroom in the IX region: role of amanita gemmata

We report 4 episodes of mushroom poisoning that ocurred before 1986 and 1990 in the province of Malleco. 25 of 36 individuals who ingested the mushroom became ill; they had an acute gastroenteritis that was followed in 7 by an acute hepatitis and in 1 by a massive upper gastrointestinal bleeding. Three subjects with fulminant hepatic failure and the subject with the massive bleeding died. Amanita gemmata (strain described as toxic in Chile since 1967) was found in 2 episodes and Amanita sp in 1. The clinical picture is similar to that described for Amanita phaloides. The treatment is symptomatic but penicillin and silymarin may have an antitoxic action. The importance of warning the population about the existence of toxic mushrooms in Chile is emphasized