Sylvie Rapior

Treatment of Amatoxin Poisoning: 20-Year Retrospective Analysis

Background: Amatoxin poisoning is a medical emergency characterized by a long incubation time lag, gastrointestinal and hepatotoxic phases, coma, and death. This mushroom intoxication is ascribed to 35 amatoxin-containing species belonging to three genera: Amanita, Galerina, and Lepiota. The major amatoxins, the α-, β-, and γ-amanitins, are bicyclic octapeptide derivatives that damage the liver and kidney via irreversible binding to RNA polymerase II. Methods: The mycology and clinical syndrome of amatoxin poisoning are reviewed. Clinical data from 2108 hospitalized amatoxin poisoning exposures as reported in the medical literature from North America and Europe over the last 20 years were compiled. Preliminary medical care, supportive measures, specific treatments used singly or in combination, and liver transplantation were characterized. Specific treatments consisted of detoxication procedures (e.g., toxin removal from bile and urine, and extra-corporeal purification) and administration of drugs. Chemotherapy included benzylpenicillin or other β-lactam antibiotics, silymarin complex, thioctic acid, antioxidant drugs, hormones and steroids administered singly, or more usually, in combination. Supportive measures alone and 10 specific treatment regimens were analyzed relative to mortality. Results: Benzylpenicillin (Penicillin G) alone and in association was the most frequently utilized chemotherapy but showed little efficacy. No benefit was found for the use of thioctic acid or steroids. Chi-square statistical comparison of survivors and dead vs. treated individuals supported silybin, administered either as mono-chemotherapy or in drug combination and N-acetylcysteine as mono-chemotherapy as the most effective therapeutic modes. Future clinical research should focus on confirming the efficacy of silybin, N-acetylcysteine, and detoxication procedures.

Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry

Exploration of natural sources for novel bioactive compounds has been an emerging field of medicine over the past decades, providing drugs or lead compounds of considerable therapeutic potential. This research has provided exciting evidence on the isolation of microbe-derived metabolites having prospective biological activities. Mushrooms have been valued as traditional sources of natural bioactive compounds for many centuries and have been targeted as promising therapeutic agents. Many novel biologically active compounds have been reported as a result of research on medicinal mushrooms. In this review, we compile the information on bioactive structure-elucidated metabolites from macrofungi discovered over the last decade and highlight their unique chemical diversity and potential benefits to novel drug discovery. The main emphasis is on their anti-Alzheimer, anti-diabetic, anti-malarial, anti-microbial, anti-oxidant, anti-tumor, anti-viral and hypocholesterolemic activities which are important medicinal targets in terms of drug discovery today. Moreover, the reader’s attention is brought to focus on mushroom products and food supplements available in the market with claimed biological activities and potential human health benefits.

Medicinal mushrooms in supportive cancer therapies: an approach to anti-cancer effects and putative mechanisms of action

Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents. Their consumption has consistently been shown to have beneficial effects on human health. Cancer is a generic term for several types of diseases that can be chronic and are responsible for a large number of deaths worldwide. Although there has been considerable progress in modern cancer therapy research, difficulties in understanding the molecular behavior of various types of cancers and the numerous side effects experienced by patients from treatments means that this whole subject area is still problematic. Thus, biological immunotherapy using natural bioactive compounds as supportive treatments in conventional cancer therapies has become in vogue. Bioactive metabolites isolated from medicinal mushrooms have shown potential successes in cancer treatment as biological immunotherapeutic agents that stimulate the immune system against cancer cells. They also act as an effective source of anti-cancer agents, capable of interfering with cellular signal transduction pathways linked to cancer development and progression. In this review we compile available data on the characteristics of medicinal mushrooms that appear to be particularly effective as biological immunotherapeutic agents. Major consideration is given to biological constituents and the putative mechanisms of action by which bioactive compounds act on the human body. Consideration is also given to the benefits that have been claimed for the use of mushrooms in treating cancer and the future prospects of using medicinal mushrooms as potent supportive candidate bioagents for treatment of cancers is discussed.

Medicinal mushrooms in prevention and control of diabetes mellitus

Diabetes mellitus is a life-threatening chronic metabolic disease caused by lack of insulin and/or insulin dysfunction, characterized by high levels of glucose in the blood (hyperglycemia). Millions worldwide suffer from diabetes and its complications. Significantly, it has been recognized that type 2 diabetes is an important preventable disease and can be avoided or delayed by lifestyle intervention. Presently, there are many chemical and biochemical hypoglycemic agents (synthetic drugs), that are used in treating diabetes and are effective in controlling hyperglycemia. However, as they may have harmful side-effects and fail to significantly alter the course of diabetic complications, natural anti-diabetic drugs from medicinal plants have attracted a great deal of attention. Medicinal mushrooms have been valued as a traditional source of natural bioactive compounds over many centuries and have been targeted as potential hypoglycemic and anti-diabetic agents. Bioactive metabolites including polysaccharides, proteins, dietary fibres, and many other biomolecules isolated from medicinal mushrooms and their cultured mycelia have been shown to be successful in diabetes treatment as biological anti-hyperglycemic agents. In this review we discuss the biological nature of diabetes and, in particular, explore some promising mushrooms that have experimental anti-diabetic properties, preventing or reducing the development of diabetes mellitus. The importance of medicinal mushrooms as agents of medical nutrition therapy and how their metabolites can be used as supportive candidates for prevention and control of diabetes is explored. Future prospects for this field of study and the difficulties and constraints that might affect the development of rational drug products from medicinal mushrooms are discussed.

Influence of dung volatiles on the process of resource selection by coprophagous beetles

Summary.Most dung beetles colonize the faeces of several vertebrate species without much discrimination, and are thus often considered as polyphagous. Recent studies have provided evidence for clear feeding preferences in scarab beetles colonizing dung of herbivore species, but little is known about these insects’ abilities to discriminate among odours from faeces of various herbivores. In this study, trophic preferences were examined using blocks of pitfall traps baited with dung from four different herbivore species, i.e., sheep, cattle, horse, and red deer, in a mountainous area of south-central France. 4941 coprophagous scarabs, belonging to 27 species, were captured. Beetles were more attracted to dung of sheep (2257 individuals) than that of cattle (1294 individuals), followed by deer dung (768 individuals) and horse dung (622 individuals). Eleven of the 27 beetle species collected had significant feeding preferences for one of the four dung types. For each insect species, trophic habits did not vary between the two different sites of trapping, an open pasture and a wooded habitat. In laboratory olfactometer bioassays, scarab beetles orientated preferentially towards the dung volatiles from the dung type they preferred in the field. Trypocopris pyrenaeus, Anoplotrupes stercorosus, and Aphodius rufipes were more attracted to volatile compounds from sheep dung, Onthophagus fracticornis significantly preferred horse dung volatiles, and Aphodius haemorrhoidalis responded positively to deer dung odours. The role of dung olfactory cues in the process of resource selection by dung beetles is discussed.

Innate olfactory preferences in dung beetles

SUMMARY The effects of insect larval diet on adult olfactory responses to host-plant or food volatiles are still debated. The induction of adult host preferences has been studied in insects with diverse ecologies, including parasitoids, flower-visitors and phytophagous species. We investigated this question for the first time in a coprophagous insect species. Larvae of the French scarab dung beetle Agrilinus constans were reared on four different artificial substrates containing dung from cattle, horse, sheep or wild boar, and responses of imagos to dung volatiles were then behaviourally tested in an olfactometer. We also reported the first analysis of the composition of different mammal dung volatiles. We showed that adult beetles were more attracted to cattle and sheep dung odours, and that larval feeding experience had no effect on the adult olfactory responses to dung volatiles. A second experiment showed that the presence of other insects inside the dung resource affects the process of dung selection by adults. We identified 64 chemical compounds from dung emissions, and showed that dung volatiles clearly differed among different mammal species, allowing olfactory discrimination by dung beetles. Our results suggest that resource selection in coprophagous insects may be based on innate olfactory preferences. Further experiments should examine whether Agrilinus adults can learn new dung odours, and whether larval diet may influence the behaviour of adults in other coprophagous species.

Role of Methylotrophy During Symbiosis Between Methylobacterium nodulans and Crotalaria podocarpa

Some rare leguminous plants of the genus Crotalaria are specifically nodulated by the methylotrophic bacterium Methylobacterium nodulans. In this study, the expression and role of bacterial methylotrophy were investigated during symbiosis between M. nodulans, strain ORS 2060T, and its host legume, Crotalaria podocarpa. Using lacZ fusion to the mxaF gene, we showed that the methylotroph genes are expressed in the root nodules, suggesting methylotrophic activity during symbiosis. In addition, loss of the bacterial methylotrophic function significantly affected plant development. Indeed, inoculation of M. nodulans nonmethylotroph mutants in C. podocarpa decreased the total root nodule number per plant up to 60%, decreased the whole-plant nitrogen fixation capacity up to 42%, and reduced the total dry plant biomass up to 46% compared with the wild-type strain. In contrast, inoculation of the legume C. podocarpa with nonmethylotrophic mutants complemented with functional mxa genes restored the symbiotic wild phenotype. These results demonstrate the key role of methylotrophy during symbiosis between M. nodulans and C. podocarpa.

Production of fumonisins and fusarins by Fusarium moniliforme from Southeast Asia

A liquid culture method for the screening of Fusarium moniliforme for the production of fusarins and fumonisins was used to test strains from Southeast Asia. An analytical method for fumonisins from liquid media was developed after evaluation of five solid phase extraction minicolumns under various conditions. Strains isolated mainly from maize from Indonesia, the Philippines and Thailand produced fusarins A, C and F as well as fumonisins B1, and B2. Among the strains, the ratio of fusarins to fumonisins production varied considerably indicating a genetic difference between strains. This is the first report of fumonisins B1, and B2 from F. moniliforme from all three countries. Fusarins are reported for the first time from strains from Indonesia and the Philippines.

Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis.

Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.

Volatile Composition of Fourteen Species of Fresh Wild Mushrooms (Boletales)

Abstract Fourty-five volatile substances of fourteen species of fresh wild mushrooms (Boletus aereus, Boletus calopus, Chroogomphus rutilus, Gomphidius glutinosus, Leccinum aurantiacum, Leccinum lepidum, Leccinum pulchrum, Leccinum querci-num, Leccinum versipelle, Paxillus atrotomentosus, Suillus bovinus, Suillus collinitus, Suillus granulatus, Suillus variegatus) have been identified by GC/MS. The main components of the fruit bodies were 1-octen-3-ol, (E)-2-octenol, 1-octen-3-one, octanol, 3-octanone, 3-octanol, N(2-phenylethyl)acetamide, benzaldehyde, limonene, geranyl acetone, farnesyl acetone and (E,E)-farnesol. Camphene and germacrene D were identified for the first time in mushrooms.