Polybrominated Diphenyl Ethers (PBDEs) and Bioaccumulative Hydroxylated PBDE Metabolites in Young Humans from Managua, Nicaragua

OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected. METHODS: We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances. RESULTS: The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites. CONCLUSIONS: Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum

HPLC-DAD and HPLC-ESI-Q-ToF characterisation of early 20th century lake and organic pigments from Lefranc archives

The characterisation of atelier materials and of the historical commercial formulation of paint materials has recently gained new interest in the field of conservation science applied to modern and contemporary art, since modern paint materials are subjected to peculiar and often unpredictable degradation and fading processes. Assessing the composition of the original materials purchased by artists can guide not only their identification in works of art, but also their restoration and conservation. Advances in characterisation methods and models for data interpretation are particularly important in studying organic coloring materials in the transition period corresponding to the late 19th-early 20th century, when many such variants or combinations were hypothetically possible in their formulations. There is thus a need for reliable databases of materials introduced in that period and for gaining chemical knowledge at a molecular level related to modern organic pigments, by state-of-the-art protocols. This paper reports on the results of a study on 44 samples of historical colorants in powder and paint tubes, containing both lake pigments and synthetic organic pigments dating from 1890 to 1926. The samples were collected at the Lefranc Archive in Le Mans (France) as a part of Project Futurahma "From Futurism to Classicism (1910-1922). Research, Art History and Material Analysis", (FIRB2012, Italian Ministry of University and Research), and were investigated using an analytical approach based on chromatographic and mass spectrometric techniques. The focus of the chemical analyses was to reveal the composition of the historical organic lake pigments including minor components, to discriminate between different recipes for the extraction of chromophore-containing molecules from the raw materials, and ultimately to distinguish between different formulations and recipes. High performance liquid chromatography (HPLC) with diode array detector (DAD) or electrospray-Quadrupole-Time of Flight tandem mass spectrometry detector (ESI-Q-ToF) were chosen given their considerable capacity to identify such complex and widespread organic materials. Although the inorganic components of the pigments were not taken into account in this survey, the specific molecular profiles provided invaluable information on the extraction procedures or synthetic strategy followed by the different producers, at different times. For instance, the use of Kopp's purpurin and garancine was highlighted, and synthetic by-products were identified. The results provided evidence that the addition of synthetic organic pigments to paint mixtures started from 1910 onwards, but they also suggest that in the formulation of high quality (surfin) colorants, natural products were still preferred. Moreover, in one of the samples the use of murexide as the colouring material was confirmed. This paper presents the first systematic and comprehensive survey on organic lakes and pigments belonging to an historical archive, by both HPLC-DAD and HPLC-ESI-Q-ToF. Specific by-products of synthetic production of pigments, which can act as specific molecular markers for dating or locating a work of art, were also identified for the first time

Natural products as starting points for future anti-malarial therapies: going back to our roots?

Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already used by the community. This first step forms a solid basis of observations, before moving to in vivo pharmacological characterization and ultimately identifying the active ingredient. A large part of the population uses herbal medicinal products despite limited numbers of well-controlled clinical studies. Increased awareness by the regulators and public health bodies of the need for safety information on herbal medicinal products also lends support to obtaining more clinical data on such products. Conclusions The relative paucity of new herbal medicinal product scaffolds active against malaria results discovered in recent years suggest it is time to re-evaluate the ‘smash and grab’ approach of randomly testing purified natural products and replace it with a patient-data led approach. This will require a change of perspective form many in the field. It will require an investment in standardisation in several areas, including: the ethnopharmacology and design and reporting of clinical observation studies, systems for characterizing anti-malarial activity of patient plasma samples ex vivo followed by chemical and pharmacological characterisation of extracts from promising sources. Such work falls outside of the core mandate of the product development partnerships, such as MMV, and so will require additional support. This call is timely, given the strong interest from researchers in disease endemic countries to support the research arm of a malaria eradication agenda. Para-national institutions such as the African Network for Drugs and Diagnostics Innovation (ANDi) will play a major role in facilitating the development of their natural products patrimony and possibly clinical best practice to bring forward new therapeutics. As in the past, with quinine, lapinone and artemisinin, once the activity of herbal medicinal products in humans is characterised, it can be used to identify new molecular scaffolds which will form the basis of the next generation of anti-malarial therapies.</p