Conception, realization and qualification of a radioactive clean room lab facility dedicated to the synthesis of radiolabeled API for human ADME studies.

The human absorption, distribution, metabolism and elimination study administering radiolabeled drugs to human volunteers is an important clinical study in the development program of new drug candidates. The manufacture of radiolabeled Active Pharmaceutical Ingredients is covered by national drug laws and may come within the scope of regulatory GMP requirements. Additionally, authorities may request an appropriate environmental zoning to minimize the risk of microbiological contaminations particularly during the synthesis of radiolabeled Active Pharmaceutical Ingredients intended for parenteral application. Thus, a radioactive clean room lab facility in line with both GMP and radiation safety regulations was installed and the environmental zoning validated by appropriate testing of technical parameters and microbial and particle monitoring. The considerations detailed in this paper cover only GMP aspects related to the synthesis of radioactive drug substance. The subsequent, final formulation step in the overall process for manufacturing of radioactive drug product for any kind of administration is not within the scope of this paper. Under these qualified and controlled environmental conditions, we are now in a position to provide radiolabeled drug substances for all kinds of drug administration including both po and iv.

Occurrence and chemotaxonomical analysis of amatoxins in Lepiota spp. (Agaricales).

About 95% of fatal mushroom poisonings worldwide are caused by amatoxins and phallotoxins mostly produced by species of Amanita, Galerina, and Lepiota. The genus Lepiota is supposed to include a high number of species producing amatoxins. In this study, we investigated 16 species of Lepiota based on 48 recently collected specimens for the presence of amatoxins by liquid chromatography coupled to a diode-array detector and mass spectrometry (UHPLC-QTOF-MS/MS). By comparing the retention times, UV absorptions, and diagnostic MS fragment ions with data obtained from the benchmark species Amanita phalloides, we detected α-amanitin and γ-amanitin in Lepiota subincarnata, α-amanitin and amaninamide in Lepiota brunneoincarnata, and ß-amanitin and α-amanitin in Lepiota elaiophylla. Phallotoxins have not been detected any of these species. Two possibly undescribed amatoxin derivatives were found in Lepiota boudieri and L. elaiophylla, as well as one further non-amatoxin compound in one specimen of L. cf. boudieri. These compounds might be used to differentiate L. elaiophylla from L. xanthophylla and species within the L. boudieri species complex. No amatoxins were detected in L. aspera, L. castanea, L. clypeolaria, L. cristata, L. erminea, L. felina, L. fuscovinacea, L. lilacea, L. magnispora, L. oreadiformis, L. pseudolilacea, L. sp. (SeSa 5), and L. subalba. By combining the occurrence data of amatoxins with a phylogenetic analysis, a monophyletic group of amatoxin containing species of Lepiota is evident. These chemotaxonomic results highlight the relevance of systematic relationships for the occurrence of amatoxins and expand our knowledge about the toxicity of species of Lepiota.

Mapping mycological ignorance - checklists and diversity patterns of fungi known for West Africa.

Scientific information about biodiversity distribution is indispensable for nature conservation and sustainable management of natural resources. For several groups of animals and plants, such data are available, but for fungi, especially in tropical regions like West Africa, they are mostly missing. Here, information for West African countries about species diversity of fungi and fungus-like organisms (other organisms traditionally studied by mycologists) is compiled from literature and analysed in its historical context for the first time. More than 16,000 records of fungi representing 4843 species and infraspecific taxa were found in 860 publications relating to West Africa. Records from the Global Biodiversity Information Facility (GBIF) database (2395 species), and that of the former International Mycological Institute fungal reference collection (IMI) (2526 species) were also considered. The compilation based on literature is more comprehensive than the GBIF and IMI data, although they include 914 and 679 species names, respectively, which are not present in the checklist based on literature. According to data available in literature, knowledge on fungal richness ranges from 19 species (Guinea Bissau) to 1595 (Sierra Leone). In estimating existing species diversity, richness estimators and the Hawksworth 6:1 fungus to plant species ratio were used. Based on the Hawksworth ratio, known fungal diversity in West Africa represents 11.4% of the expected diversity. For six West African countries, however, known fungal species diversity is less than 2%. Incomplete knowledge of fungal diversity is also evident by species accumulation curves not reaching saturation, by 45.3% of the fungal species in the checklist being cited only once for West Africa, and by 66.5% of the fungal species in the checklist reported only for a single country. The documentation of different systematic groups of fungi is very heterogeneous because historically investigations have been sporadic. Recent opportunistic sampling activities in Benin showed that it is not difficult to find specimens representing new country records. Investigation of fungi in West Africa started just over two centuries ago and it is still in an early pioneer phase. To promote proper exploration, the present checklist is provided as a tool to facilitate fungal identification in this region and to aid conceptualisation and justification of future research projects. Documentation of fungal diversity is urgently needed because natural habitats are being lost on a large scale through altered land use and climate change.

Diversity and taxonomy of Tricholoma species from Yunnan, China, and notes on species from Europe and North America.

Although taxonomic knowledge on Tricholoma (Agaricales, Basidiomycota) is fairly comprehensive in northwest Europe, knowledge of the global diversity and distribution of Tricholoma spp. is still sparse. In this study, the diversity and distribution of some Tricholoma spp. are analyzed by morphological and molecular methods based on 70 collections from Yunnan, China, 45 from central Europe, 32 from Colorado, USA, 9 from Japan, and 3 from Ukraine. A Holarctic distribution is suggested for several species, based on collections and nuc rDNA internal transcribed spacer ITS1-5.8S-ITS2 (ITS) sequences. Six species new to science are formally described from Yunnan: five in existing sections, Tricholoma forteflavescens, T. olivaceoluteolum, T. melleum, T. olivaceum, and T. sinoportentosum, and one, T. muscarioides, in the newly described section Muscaria alongside several previously described species. Additional putatively new species cannot be formally described because they lack sufficient material. Tricholoma foliicola is recognized as a species of the genus Gerhardtia.