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Kohl T.,Justus Liebig University | Ziemann M.,University of Bonn | Weinbach J.,University of Bonn | Tchatcheva K.,University of Bonn | And 2 more authors.
Journal of Laparoendoscopic and Advanced Surgical Techniques | Year: 2010

Background: Partial amniotic carbon dioxide insufflation (PACI) during fetoscopic interventions greatly improves visualization of intraamniotic contents. The purpose of this study was to assess any histologically discernable effects from this approach on the fetal brain after long-term survival in sheep. Methods: Six pregnant ewes between 63 and 92 days of gestation underwent PACI after fetoscopic intraamniotic access. Insufflation pressures ranged between 7 and 15mm Hg (mean 11.7; median 12.5). Insufflation times ranged between 45 and 80 minutes (mean 55.8 minutes; median 52.5) and depended on the duration of various percutaneous fetoscopic maneuvers (e.g., posturing, fetal transesophageal electrocardiography, and chronic fetal vascular access) that were tested during these studies. After fetal spontaneous delivery between 147 and 150 days of gestation, 5 of the lambs were observed for abnormal neurological symptoms. The last ewe and her sheep were terminated at 133 days of gestation for humane reasons. All six brains were examined for hemorrhage, embolism, infarctions, inflammatory changes, and abnormal cortical maturation. An unoperated sibling was available as a control. Results: The 5 sheep that were spontaneously delivered exhibited no abnormal neurological findings. In all 6 sheep, PACI did not result in any histologically discernable damage to their brain in these long-term studies. Maternal and fetal complications were not observed during or after the approach. Conclusion: The application of PACI during minimally invasive fetoscopic interventions seems safe for the fetal brain. Due to the still limited clinical experience with PACI, continued assessment of its maternal and fetal risks as well as management are required. © 2010 Mary Ann Liebert, Inc.

Stegger L.,University of Tubingen | Stegger L.,University of Mu Nster | Martirosian P.,University of Tubingen | Schwenzer N.,University of Tubingen | And 8 more authors.
Acta Radiologica | Year: 2012

Background: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear. Purpose: To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device. Material and Methods: ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 128 and 192 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors. Results: Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51+9 and 51 +7 mL/100 g/min for the 128 128 and 192 192 matrices (stand-alone MR, 57+2 and 55+5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 192 matrix size (P, 0.01), the relative signal change (dS) was significantly lower for the 192 192 matrix size (P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality. Conclusion: ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.

Roth W.,University of Leipzig | Kumar V.,University of Leipzig | Beer H.-D.,University of Zurich | Richter M.,University of Leipzig | And 12 more authors.
Journal of Cell Science | Year: 2012

Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) are major constituents of the intermediate filament cytoskeleton in suprabasal epidermis. KRT1 mutations cause epidermolytic ichthyosis in humans, characterized by loss of barrier integrity and recurrent erythema. In search of the largely unknown pathomechanisms and the role of keratins in barrier formation and inflammation control, we show here that Krt1 is crucial for maintenance of skin integrity and participates in an inflammatory network in murine keratinocytes. Absence of Krt1 caused a prenatal increase in interleukin-18 (IL-18) and the S100A8 and S100A9 proteins, accompanied by a barrier defect and perinatal lethality. Depletion of IL-18 partially rescued Krt-/- mice. IL-18 release was keratinocyte-autonomous, KRT1 and caspase-1 dependent, supporting an upstream role of KRT1 in the pathology. Finally, transcriptome profiling revealed a Krt1-mediated gene expression signature similar to atopic eczema and psoriasis, but different from Krt5 deficiency and epidermolysis bullosa simplex. Our data suggest a functional link between KRT1 and human inflammatory skin diseases. © 2012. Published by The Company of Biologists Ltd.

Meyer W.,University of Mu Nster | Seiler T.-B.,RWTH Aachen | Schwarzbauer J.,RWTH Aachen | Hollert H.,RWTH Aachen | Achten C.,University of Mu Nster
Science of the Total Environment | Year: 2014

Investigations of the bioavailability and toxicity of polycyclic aromatic compounds (PAC) have rarely considered the heterogeneity of coals and the impact of more polar PAC besides polycyclic aromatic hydrocarbons (PAH).Earlier, we investigated the toxicity of eight heterogeneous coals and their extracts. In the present study, the hazard potential with respect to mechanism-specific toxicity of polar fractions of dichloromethane extracts from coals was studied. Polar extract fractions of all coal types except for anthracite induced EROD activity (determined in RTL-W1 cells), independent of coal type (Bio-TEQs between 23 ± 16 and 52 ± 22. ng/g). The polar fractions of all bituminous coal extracts revealed mutagenic activity (determined using the Ames Fluctuation test). No significant mutation induction was detected for the polar extract fractions from the lignite, sub-bituminous coal and anthracite samples, which indicates a higher dependency on coal type for polar PAC here.Additionally, information on bioavailability was derived from a bioaccumulation test using the deposit-feeding oligochaete Lumbriculus variegatus which was exposed for 28. days to ground coal samples. Despite the high toxic potential of most coal extracts and a reduced biomass of Lumbriculus in bituminous coal samples, bioaccumulation of PAH and mortality after 28 days were found to be low. Limited bioaccumulation of PAH (up to 3.6 ± 3.8 mg/kg EPA-PAH) and polar PAC were observed for all coal samples. A significant reduction of Lumbriculus biomass was observed in the treatments containing bituminous coals (from 0.019 ± 0.004. g to 0.046 ± 0.011 g compared to 0.080 ± 0.025 g per replicate in control treatments).We conclude that bioavailability of native PAC from coals including polar PAC is low for all investigated coal types. In comparison to lignite, sub-bituminous coals and anthracite, the bioavailability of PAC from bituminous coals is slightly increased. © 2014 Elsevier B.V.

Geduhn A.,Julius Kuhn Institute | Geduhn A.,University of Mu Nster | Esther A.,Julius Kuhn Institute | Schenke D.,Julius Kuhn Institute | And 2 more authors.
Science of the Total Environment | Year: 2014

Worldwide pest rodents on livestock farms are often regulated using anticoagulant rodenticides (ARs). Second generation ARs in particular can cause poisoning in non-target species due to their high toxicity and persistence. However, research on exposure of small mammals is rare. We systematically investigated spatial and temporal exposure patterns of non-target small mammals in a large-scale replicated study. Small mammals were trapped at different distances to bait stations on ten farms before, during and after brodifacoum (BR) bait application, and liver samples of 1178 non-target small mammals were analyzed for residues of eight ARs using liquid chromatography coupled with tandem mass spectrometry. BR residues were present in 23% out of 742 samples collected during and after baiting. We found clear spatial and temporal exposure patterns. High BR residue concentrations mainly occurred within 15. m from bait stations. Occurrence and concentrations of residues significantly decreased with increasing distance. This pattern was found in almost all investigated taxa. After baiting, significantly more individuals contained residues than during baiting but concentrations were considerably lower. Residue occurrence and concentrations differed significantly among taxa, with the highest maximal residue concentrations in Apodemus species, which are protected in Germany. Although Sorex species are known to be insectivorous we regularly found residues in this genus. Residues of active agents other than brodifacoum were rare in all samples. The confirmation of substantial primary exposure in non-target small mammals close to the baiting area indicates considerable risk of secondary poisoning of predators, a pathway that was possibly underestimated until now. Our results will help to develop risk mitigation strategies to reduce risk for non-target small mammals, as well as their predators, in relation to biocidal AR usage. © 2014 Elsevier B.V.

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