Toxicology of microcystins with reference to cases of human intoxications and epidemiological investigations of exposures to cyanobacteria and cyanotoxins.

Blooms of cyanobacteria have been documented throughout history, all over the world. Mass populations of these organisms typically present hazards to human health and are known for the production of a wide range of highly toxic metabolites-cyanotoxins, of which among the most common and most investigated are the microcystins. The toxicity of the family of microcystin congeners to animal and cell models has received much attention; however, less is known about their negative effects on human health, whether via acute or chronic exposure. Useful information may be acquired through epidemiological studies since they can contribute to knowledge of the relationships between cyanotoxins and human health in environmental settings. The aim of this review is to compile and evaluate the available published reports and epidemiological investigations of human health incidents associated with exposure to mass populations of cyanobacteria from throughout the world and to identify the occurrence and likely role of microcystins in these events. After an initial screening of 134 publications, 42 publications (25 on the chronic and 17 on the acute effects of cyanotoxins) describing 33 cases of poisonings by cyanobacterial toxins in 11 countries were reviewed. The countries were Australia, China, Sri Lanka, Namibia, Serbia, Sweden, UK, Portugal, Brazil, USA, and Canada. At least 36 publications link cyanobacteria/cyanotoxins including microcystins to adverse human health effects. The studies were published between 1960 and 2016. Although the scattered epidemiological evidence does not provide a definitive conclusion, it can serve as additional information for the medical assessment of the role of microcystins in cancer development and other human health problems. This paper discusses the major cases of cyanotoxin poisonings as well as the strengths, weaknesses, and importance of the performed epidemiological research. This study also proposes some recommendations for future epidemiological work.

Ecotoxicology inside the gut: impact of heavy metals on the mouse microbiome.

BACKGROUND: The gut microbiota is critical for intestinal homeostasis. Recent studies have revealed the links between different types of dysbiosis and diseases inside and outside the intestine. Environmental exposure to pollutants (such as heavy metals) can also impair various physiological functions for good health. Here, we studied the impact of up to 8 weeks of oral lead and cadmium ingestion on the composition of the murine intestinal microbiome. RESULTS: Pyrosequencing of 16S RNA sequences revealed minor but specific changes in bacterial commensal communities (at both family and genus levels) following oral exposure to the heavy metals, with notably low numbers of Lachnospiraceae and high numbers levels of Lactobacillaceae and Erysipelotrichaceacae (mainly due to changes in Turicibacter spp), relative to control animals. CONCLUSIONS: Non-absorbed heavy metals have a direct impact on the gut microbiota. In turn, this may impact the alimentary tract and overall gut homeostasis. Our results may enable more accurate assessment of the risk of intestinal disease associated with heavy metal ingestion.

Prevalence of Deg Nala disease in eastern India and its reproduction in buffaloes by feeding Fusarium oxysporum infested rice straw.

OBJECTIVE: To undertake a study on prevalence of Deg Nala disease in eastern states of India and to reproduce the disease in buffaloes by the Fusarium spp., isolated from the affected region. METHODS: During this investigation, a survey was conducted covering four states of eastern region to identify the Deg Nala cases as well as to isolate and characterize the causative agent(s). An experimental study was carried out to reproduce the disease in healthy male buffaloes (2-3 years age) by randomly dividing them into five groups (four in each group). Each individual group was fed with rice straw artificially infested with either of the two representative isolates of Fusarium oxysporum (F. oxysporum) (F01, F02) or representative reference strains of Fusarium equiseti (F. equiseti) (ITCCF-2470) and Fusarium moniliforme (F. moniliforme) (ITCCF-4821) for 30 days, whereas the control group was fed with normal rice straw only. RESULTS: A total of 658 Deg Nala cases were recorded and 12 Fusarium isolates were identified from the mouldy rice straw collected from these affected areas. The characterization of the isolates revealed three species viz., F. oxysporum, F. equiseti and F. moniliforme, among which F. oxysporum was predominant. The disease was artificially reproduced in three buffaloes in F01 group and one in F02 group within 20-23 days by feeding F. oxysporum infested rice straw which resembled the clinical symptoms and gross lesions of natural Deg Nala cases. CONCLUSIONS: The field investigation and laboratory studies, including experimental production of Deg Nala disease suggest the possible involvement of mycotoxins. However, further investigations needs to be done to understand nature of the toxic factors involved in production of the Deg Nala disease.

Identification of a benthic microcystin-producing filamentous cyanobacterium (Oscillatoriales) associated with a dog poisoning in New Zealand.

In November 2008 a dog died soon after ingesting benthic "algal" mat material from the Waitaki River, New Zealand. Based on a morphological examination of environmental material, the causative organism was putatively identified as the filamentous cyanobacterium Phormidium sp. Two strains (VUW25 and CYN61) were isolated and cultured to enable further taxonomic and cyanotoxin characterisation. Phylogenetic analyses based on a region of the 16S rRNA gene sequence, intergenic spacer (ITS) region and the mcyE gene demonstrated that the species was likely to be a new Planktothrix species that is either benthic or has a biphasic life cycle. Using liquid chromatography-mass spectrometry (LC-MS), microcystin-LR, [D-Asp(3), Dha(7)] microcystin-LR, [D-Asp(3)] microcystin-LR, and minor proportions of [D-Asp(3), ADMAdda(5)] microcystin-LhR were identified. This is the first report of [D-Asp(3)] microcystin-LR, [D-Asp(3), Dha(7)] microcystin-LR and an ADMAadda variant in New Zealand. No cylindrospermopsins, saxitoxins or anatoxins were detected. Dog deaths caused by the consumption of cyanobacterial mats containing anatoxins have previously been reported in New Zealand. To our knowledge, however, this is the first instance of a benthic microcystin-producing species causing an animal death in New Zealand.

Poisoning of dogs with tremorgenic Penicillium toxins.

Fungi in the genus Penicillium, particularly P. crustosum, produce tremorgenic mycotoxins, as well as suspected tremorgenic compounds. The accidental intoxication of six dogs with such toxins are reported. The clinical signs included vomiting, convulsions, tremors, ataxia, and tachycardia, all of which are indicators of intoxications affecting the nervous system. This symptomatology caused us to think that the dog poisoning was the result of tremorgenic mycotoxins. One dog was euthanized in the acute phase, while three others recovered completely within a few days. However, neurological symptoms were still observed four months after the poisoning of two of the dogs. One of these recovered completely within the next 2-3 months, while the other still suffers from ataxia three years later. Available samples of feed, stomach content and/or tissues from the intoxications were subjected to mycological and chemical analysis. Penitrem A was found in all reported poisonings and roquefortine C in all cases when this toxin was included in the analysis. The producer of these toxins, Penicillium crustosum, was detected in all cases where material suitable for mycological examinations (feed or vomit) was available. To our knowledge, this is the first report documenting the presence of penitrems and roquefortine C in organs from poisoned dogs. Furthermore, the report indicates that the recovery period after severe poisonings with P. crustosum may be protracted.

Growth and hepatic in vitro metabolism of ergotamine in mice divergently selected for response to endophyte toxicity.

This study investigated if genetic differences exhibited in endophyte-resistant and -susceptible mouse lines had persisted after 13 generations in which the integrity of lines was maintained yet selection ceased. Experimental groups were mouse lines fed an endophyte-free (E-) or -infected (E+) diet. The in vitro metabolism of the ergot alkaloid ergotamine in mouse liver microsomes was characterized by LC-MS/MS and compared between both lines before and after exposure to E+ feed. No difference in the average daily weight gain of pups between resistant and susceptible mice was observed on the E+ diet. Thus, for the weight gain selection criterion under study, the difference established between the two lines appears not to have persisted over the extended period of relaxed selection. Microsomal incubations produced nine predominate peaks in the HPLC assay. The peaks were confirmed by LC-MS/MS to be ergotamine, ergotamine epimer, monohydroxylated metabolites (M1, M2, M1e, M2e) and dihydroxylated metabolites (M3--5). A gender difference for metabolite formation was observed on the E- diet, in that females produced a greater amount of M1, M1e and M3--5 than males. When challenged with the E+ diet, mice showed differences in concentration of M3 for line (resistant > susceptible) and gender (female > male) and of M4 and M5 for gender (female > male). Gender differences in the metabolism of ergotamine have not been shown before in these lines of mice or other species used to study ergot alkaloid metabolism. This adds a potential source of variation in the susceptibility to fescue toxicity not explored previously and would be of value to investigate further.

Contamination and compensation: Gruinard as a 'menace to the mainland'.

The decades-long contamination of Gruinard Island by anthrax is now a well-known part of the history of biological weapons (BW) development, as well as that of military encroachments in the Scottish Highlands and Islands (and the authorities' rather less persistent efforts at damage limitation). Some accounts have included the related episode, reportedly well-remembered by local people, of anthrax contamination on the mainland close to Gruinard. This occurred in 1942--43, when BW experiments were conducted on the island as part of the war effort by scientists from Porton Down under the auspices of the British government. After much top-level discussion, payments were made to the owners of animals that had died as a result of the contamination. The episode had a bearing on discussions about the future of the island and on subsequent policy with regard to the siting, conduct and secrecy of BW experiments.

Acidentes provocados por Physalia sp (caravelas): 238 casos relatados no litoral catarinense / Accidents caused by physalia sp (man of war): 238 cases reported in the catarinense seashore

A espécie Physalia sp é o tipo de caravela mais freqüente e de maior atividade tóxica do litoral brasileiro, causando acidentes por contatos, com sintomatologia de dor, eritema, prurido, contrações musculares, vômitos, podendo ocorrer também hemólise, insuficiência renal e choque anafilático. Analisou-se a frequencia destes acidentes, notificados ao centro de Informações Toxicológicas (CIT/SC) no período de 1984 a 1996....