OBJECTIVE: Periodontitis, mostly associated with Porphyromonas gingivalis, has frequently been related to adverse pregnancy outcomes. We therefore investigated whether lipopolysaccharides of P. gingivalis (Pg-LPS) induced pregnancy complications in the rat.METHODS: Experiment 1: pregnant rats (day 14) received increasing Pg-LPS doses (0.0-50.0 μg kg-1 bw; n = 2/3 p per dose). Maternal intra-aortic blood pressure, urinary albumin excretion, placental and foetal weight and foetal resorptions were documented. Experiment 2: 10.0 μg kg-1 bw (which induced the highest blood pressure together with decreased foetal weight in experiment 1) or saline was infused in pregnant and non-pregnant rats (n = 7/9 p per group). Parameters of experiment 1 and numbers of peripheral leucocytes as well as signs of inflammation in the kidney and placenta were evaluated.RESULTS: Pg-LPS infusion in pregnant rats increased maternal systolic blood pressure, reduced placental weight (dose dependently) and decreased foetal weight and induced foetal resorptions. It, however, did not induce proteinuria or a generalised inflammatory response. No effects of Pg-LPS were seen in non-pregnant rats.CONCLUSION: Pg-LPS increased maternal blood pressure, induced placental and foetal growth restriction, and increased foetal resorptions, without inducing proteinuria and inflammation. Pg-LPS may therefore play a role in pregnancy complications induced by periodontitis.
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Human exposure to polybrominated diphenyl ethers (PBDEs) can occur via ingestion of indoor dust, inhalation of PBDE-contaminated air and dust-bound PBDEs. However, few studies have examined the pulmonary toxicity of particle-bound PBDEs, mainly due to the lack of an appropriate particle-cell exposure system. In this study we developed an in vitro exposure system capable of generating particle-bound PBDEs mimicking dusts containing PBDE congeners (PBDEs 35, 47 and 99) and delivering them directly onto lung cells grown at an air–liquid interface (ALI). The silica particles and particles-coated with PBDEs ranged in diameter from 4.3 to 4.5 μm and were delivered to cells with no apparent aggregation. This experimental set up demonstrated high reproducibility and sensitivity for dosing control and distribution of particles. All exposure of cells to PBDE-bound particles significantly decreased cell viability and induced reactive oxygen species generation in A549 and NCI-H358 cells. In male Sprague-Dawley rats exposed via intratracheal insufflation (0.6 mg/rat), particle-bound PBDE exposures induced inflammatory responses with increased recruitment of neutrophils to the lungs compared to sham-exposed rats. The present study clearly indicates the potential of our exposure system for studying the toxicity of particle-bound compounds.Abstract of the paper published by Elsevier. The whole paper can be obtained via: http://www.sciencedirect.com/science/article/pii/S0300483X14000067#
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From the article: Abstract Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the carcinogenicity study (True Negatives). Cellular hypertrophy appeared to be an unreliable predictor of carcinogenicity. The negative predictivity, the measure of the compounds evaluated that did not show any putative preneoplastic lesion in de sub-chronic studies and were negative in the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The specificity, the accuracy of the sub-chronic study to correctly identify non-carcinogens was 90%. When the chemicals which induced tumours generally considered not relevant for humans (33 out of 37 False Negatives) are classified as True Negatives, the negative predictivity amounts to 97%. Overall, the results of this retrospective study support the concept that chemicals showing no histopathological risk factors for neoplasia in a sub-chronic study in rats may be considered non-carcinogenic and do not require further testing in a carcinogenicity study.
In recent years, disasters are increasing in numbers, location, intensity and impact; they have become more unpredictable due to climate change, raising questions about disaster preparedness and management. Attempts by government entities at limiting the impact of disasters are insufficient, awareness and action are urgently needed at the citizen level to create awareness, develop capacity, facilitate implementation of management plans and to coordinate local action at times of uncertainty. We need a cultural and behavioral change to create resilient citizens, communities, and environments. To develop and maintain new ways of thinking has to start by anticipating long-term bottom-up resilience and collaborations. We propose to develop a serious game on a physical tabletop that allows individuals and communities to work with a moderator and to simulate disasters and individual and collective action in their locality, to mimic real-world scenarios using game mechanics and to train trainers. Two companies–Stratsims, a company specialized in game development, and Society College, an organization that aims to strengthen society, combine their expertise as changemakers. They work with Professor Carola Hein (TU Delft), who has developed knowledge about questions of disaster and rebuilding worldwide and the conditions for meaningful and long-term disaster preparedness. The partners have already reached out to relevant communities in Amsterdam and the Netherlands, including UNUN, a network of Ukrainians in the Netherlands. Jaap de Goede, an experienced strategy simulation expert, will lead outreach activities in diverse communities to train trainers and moderate workshops. This game will be highly relevant for citizens to help grow awareness and capacity for preparing for and coping with disasters in a bottom-up fashion. The toolkit will be available for download and printing open access, and for purchase. The team will offer training and facilitate workshops working with local communities to initiate bottom-up change in policy making and planning.
