Current reference values of ALT, AST, and GGT serum levels were calculated for children between 11 months and 16.0 years, using modern analytical and statistical methods. This study extends the current knowledge about transaminases by revealing influences of age, sex, BMI, and puberty on serum concentrations of all three parameters and has for these parameters one of the largest sample sizes published so far. (Hepatology 2017).

Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a natural inhibitor of metalloproteinases involved in matrix degradation and ectodomain shedding of many cell-surface proteins, including death receptors and/or their ligands. In the present study, we examined the role of TIMP-3 in Fas-mediated neuronal cell death following cerebral ischemia, using both gene deletion and pharmacological approaches. In culture, exposure of primary cortical neurons to 2 h of oxygen-glucose deprivation (OGD) resulted in delayed neuronal cell death that was dependent on activation of the death receptor, Fas. Cortical cultures derived from timp-3 À/À mice displayed partial resistance against OGD-induced neuronal cell death and also displayed increased shedding of Fas ligand (FasL) into the culture media, compared to wild-type control cultures. Both the increased neuroprotection and increased FasL shedding in timp-3 À/À cultures were reversed by addition of exogenous metalloproteinase inhibitors, recombinant TIMP-3 or GM6001. In vivo, timp-3 À/À mice showed marked resistance to a brief (30 min) middle cerebral artery occlusion (MCAO), but were not protected against more severe lesions induced by 90 min of MCAO. These studies demonstrate that TIMP-3 facilitates Fas-mediated neuronal cell death following OGD and plays a pro-apoptotic role in mild cerebral ischemia.

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We found evidence for a hypercoagulable state in patients with sCAD as indicated by a shortened aPTT, which was associated with a trend to an increased leucocyte count at the same time. Our findings first strengthen the hypothesis that inflammation critically impacts on the occurrence of sCAD, and second linked this condition with a marked affection of the coagulation system.

Abb. 1. Effekte der systemischen und lokalen thrombolytischen Therapie auf das Fibrinogen und die aktivierte partielle Thromboplastinzeit (Details s. Text)

ObjectivesIn the present study, we examined the relation between socioeconomic status (SES) and the physiological distribution of iron-related blood parameters.DesignThis is a cross-sectional analysis of longitudinal population-based cohort study.SettingBased on a sample of healthy participants from a German research centre, various blood parameters and values of clinical examinations and questionnaires were collected.ParticipantsA total of 1206 healthy volunteers aged 2.5 to 19 years, one child per family randomly selected, were included.Primary and secondary outcome measuresAssociations between the SES of children by Winkler-Stolzenberg Index (WSI) and its dimensions (income, education, occupation) and iron-related blood parameters (haemoglobin, ferritin and transferrin) were analysed by linear regression analyses. Gender and pubertal stage were included as covariables. Additionally, associations between SES of children by WSI and physical activity (side-to-side jumps, push-ups) as well as body mass index (BMI) were analysed by linear regression analyses.ResultsChildren with high WSI or family income showed significantly increased z-scores for haemoglobin (P=0.046; P<0.001). Children with increased WSI or family income showed significantly lower z-scores for transferrin (P<0.001). There was a significant correlation between haemoglobin and gender (P<0.001) and between transferrin and pubertal stage (P=0.024). Furthermore, physical activity was positively correlated and BMI was negatively correlated with WSI (P<0.001).DiscussionOur data show an association between SES and the distribution of iron-dependent parameters. Lower SES is correlated with lower values for haemoglobin and higher values for transferrin. Furthermore, we demonstrate that physical activity and BMI are associated with SES. Whereas higher SES is correlated with higher values for physical activity and lower BMI. Our parameters are standardised as z-scores with the advantages that the results are comparable across different age groups and present physiological courses.Trial registration numberNCT02550236; Results.