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Eilers B.,Max Planck Institute for Infection Biology | Mayer-Scholl A.,Max Planck Institute for Infection Biology | Mayer-Scholl A.,Bundesinstitut For Risikobewertung Bfr | Walker T.,New York University | And 4 more authors.
Cellular Microbiology | Year: 2010

Summary: Shigella flexneri is an enteric pathogen that causes massive inflammation and destruction of the human intestinal epithelium. Neutrophils are the first cells of the innate immune system recruited to the site of infection. These cells can attack microbes by phagocytosis, Neutrophil Extracellular Trap (NET) formation and degranulation. Here, we investigated how neutrophil degranulation affects virulence and show that exposure of Shigella to granular proteins enhances infection of epithelial cells. During this process, cationic granular proteins bind to the Shigella surface causing increased adhesion which ultimately leads to hyperinvasion. This effect is mediated by changes in the surface charge, since a lipopolysaccharide (LPS) mutant with a negative surface shows enhanced hyperinvasion compared with wild-type Shigella. We propose that Shigella evolved to use host defence molecules to enhance its virulence and subvert the innate immune system. © 2010 Blackwell Publishing Ltd.

Pfeil R.,Bundesinstitut For Risikobewertung Bfr
Aktuelle Ernahrungsmedizin | Year: 2010

In recent years, multiple pesticide residues have increasingly been detected in foods, especially in table grapes, strawberries, redcurrants and blackcurrants, and citrus fruit. On the one hand, this is happening as a consequence of effective analytical tests for pesticides, which enable better detection of a larger number of substances, at ever smaller dosages, than in the past. On the other hand, today's agricultural practices contribute to the occurrence of multiple pesticide residues. The required product quality can be achieved only by using a wide spectrum of pesticides with selective effects. The health impact assessment for multiple residues presents a challenge since threshold values have thus far deduced only for single pesticides, whereas in reality, consumers are exposed to a multitude of substances. In the hazard assessment of substances whose effects are similar can be assumed to be additive. In substances whose effects are dissimilar the health risk associated with a mixture is determined by its most dangerous ingredient. © Georg Thieme Verlag KG Stuttgart · New York.

Batz F.M.,Free University of Berlin | Klipper W.,Free University of Berlin | Korting H.C.,Ludwig Maximilians University of Munich | Henkler F.,Bundesinstitut For Risikobewertung Bfr | And 5 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

Reconstructed human epidermis (RHE) is used in non-animal testing for hazard analysis and reconstructed human skin (RHS) gains growing interest in preclinical drug development. RHE and RHS have been characterised regarding their barrier function, but knowledge about biotransformation capacity in these constructs and in human skin remains rather poor. However, metabolising enzymes can be highly relevant for the efficacy of topical dermatics as well as genotoxicity and sensitisation. We have compared the esteratic cleavage of the prednisolone diester prednicarbate and the enzyme kinetic parameters (V max and S0.5) of the model substrate fluorescein diacetate (FDA) in commercially available RHS and RHE with excised human skin and monolayer cultures of normal and immortalised human keratinocytes and of fibroblasts. Formation of the main metabolite prednisolone and of fluorescein ranked as: RHS∼RHE > excised human skin and keratinocytes > fibroblasts, respectively. Because of the aromatic probe, however, V max of FDA cleavage did not show a linear relationship with prednicarbate metabolism. In conclusion, RHE and RHS may be useful to quantitatively address esterase activity of human skin in drug development and hazard analysis, although an increased activity compared to native human skin has to be taken into account. © 2013 Elsevier B.V. All rights reserved.

Hahn A.,Bundesinstitut For Risikobewertung Bfr | Begemann K.,Bundesinstitut For Risikobewertung Bfr | Sturer A.,Universitatsmedizin Mainz
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2014

Cases of poisoning account for a distinct share of accidents in Germany, which is particularly high for accidents involving children. Cases of poisoning resulting from suicidal intent or abuse are not counted as accidents. Compared to other cases of disease and accidents, the numerical documentation of cases of poisoning is inadequate. Presently, there is no institution in Germany that could make available representative and meaningful data on the current state of poisoning. Owing to intensive scientific cooperation between the poison information centers (funded by the federal states) and the Poison and Product Documentation Center at the Federal Institute for Risk Assessment (BfR DocCenter) as well as to international cooperation, harmonized and standardized tools have been developed for the appropriate documentation and reporting of procedures to account for poisoning accidents. The first evaluation for 2005-2012 based on published and processed figures for the Federal Republic of Germany yielded the following results: Of approximately 230,000 telephone inquiries received in 2012, about 207,000 involved exposure of humans to different noxae. An annual increase of 3-5∈% was recorded. For 2011, analyses of subsets processed by means of standardized methods yielded the following results: Medicines were involved in about 39∈% of the cases recorded (of these, medicinal products for humans in 99∈%); chemical/physicochemical agents in about 26∈% (of these, cleaning and maintenance products in 46∈%); products of daily use in about 14∈% (of these, cosmetics in 40∈%); and plants in about 10∈%. More than 90∈% of cases were acute poisoning and less than 5∈%, chronic poisoning. Regarding the degree of severity of poisoning, an asymptomatic course was reported for 44∈% of the cases; minor manifestations were experienced in 30∈%, moderate ones in 6∈%, and severe manifestations in 2∈% of the cases recorded. Fatal cases were rare (<∈0.1∈%). The majority of cases (67∈%) were caused by poisoning accidents, followed by suicidal action (20∈%), with abuse and industrial poisoning (4∈%) in third position; 1∈% of the cases of poisoning were attributed to adverse drug reactions (ADR) and mistaking a medicinal product for another one. Infants aged 1-2 years have the highest risk of poisoning. A panel of the BfR Committee for the Assessment of Poisonings has already developed proposals for a national monitoring scheme of poisoning incidents. The aim is to prepare annual reports similar to the report of the National Poison Data System (NPDS) maintained by the American Association of Poison Control Centers (AAPCC) in the USA. © 2014 Springer-Verlag Berlin Heidelberg.

Wolfle D.,Bundesinstitut For Risikobewertung Bfr | Pfaff K.,Bundesinstitut For Risikobewertung Bfr
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2010

For materials and articles intended to come in contact with food - particularly for substances from plastics (e.g., monomers, additives) - there are comprehensive European regulations based on toxicological evaluations. Other food contact materials, e.g., paper and rubber, are covered by resolutions established by the European Council without additional evaluations, while in Germany substances from these materials are toxicologically evaluated by the Federal Institute for Risk Assessment (BfR) and are included in the "BfR recommendations". Some further areas of food contact materials are not regulated by European or by national regulations (e.g., substances from printing inks). Recently, new European regulations for recycled plastics intended for food contact and for active and intelligent materials and articles have been released. Future challenges are the risk assessment of contaminants and reaction products from the production of food contact substances, which may migrate into the food in only tiny amounts, and of complex mixtures of substances, e.g., of hormone-like substances (endocrine disruptors). © 2010 Springer Medizin Verlag.

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