Thrombocyta és thrombocyta eredetű mikropartikulum vizsgálatok súlyos szepszisben

7

Interleukin-1β Interferes with Epidermal Homeostasis through Induction of Insulin Resistance: Implications for Psoriasis Pathogenesis

Response pathways of the metabolic and the immune system have been evolutionary conserved, resulting in a high degree of integrated regulation. Insulin is a central player in the metabolic system and potentially also in the homeostasis of the skin. Psoriasis is a frequent and often severe autoimmune skin disease, clinically characterized by altered epidermal homeostasis, of which the molecular pathomechanisms are only little understood. In this study, we have examined a potential role for insulin signaling in the pathogenesis of this disease. We show that IL-1β is present in high quantities in tissue fluid collected via microdialysis from patients with psoriasis; these levels are reduced under successful anti-psoriatic therapy. Our results suggest that IL-1β contributes to the disease by dual effects. First, it induces insulin resistance through p38MAPK (mitogen-activated protein kinase), which blocks insulin-dependent differentiation of keratinocytes, and at the same time IL-1β drives proliferation of keratinocytes, both being hallmarks of psoriasis. Taken together, our findings point toward insulin resistance as a contributing mechanism to the development of psoriasis; this not only drives cardiovascular comorbidities, but also its cutaneous phenotype. Key cytokines inducing insulin resistance in keratinocytes and kinases mediating their effects may represent attractive targets for novel anti-psoriatic therapies

Future extreme events in European climate: an exploration of regional climate model projections

This paper presents an overview of changes in the extreme events that are most likely to affect Europe in forthcoming decades. A variety of diagnostic methods are used to determine how heat waves, heavy precipitation, drought, wind storms, and storm surges change between present (1961-90) and future (2071-2100) climate on the basis of regional climate model simulations produced by the PRUDENCE project. A summary of the main results follows. Heat waves - Regional surface warming causes the frequency, intensity and duration of heat waves to increase over Europe. By the end of the twenty first century, countries in central Europe will experience the same number of hot days as are currently experienced in southern Europe. The intensity of extreme temperatures increases more rapidly than the intensity of more moderate temperatures over the continental interior due to increases in temperature variability. Precipitation - Heavy winter precipitation increases in central and northern Europe and decreases in the south; heavy summer precipitation increases in north-eastern Europe and decreases in the south. Mediterranean droughts start earlier in the year and last longer. Winter storms - Extreme wind speeds increase between 45°N and 55°N, except over and south of the Alps, and become more north-westerly than cuurently. These changes are associated with reductions in mean sea-level pressure, leading to more North Sea storms and a corresponding increase in storm surges along coastal regions of Holland, Germany and Denmark, in particular. These results are found to depend to different degrees on model formulation. While the responses of heat waves are robust to model formulation, the magnitudes of changes in precipitation and wind speed are sensitive to the choice of regional model, and the detailed patterns of these changes are sensitive to the choice of the driving global model. In the case of precipitation, variation between models can exceed both internal variability and variability between different emissions scenario

The Role of Whole Blood Impedance Aggregometry and Its Utilisation in the Diagnosis and Prognosis of Patients with Systemic Inflammatory Response Syndrome and Sepsis in Acute Critical Illness

Objective: To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count). Methods: We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. Results: 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p = 0.001, Collagen 102.6±33.0 vs 79.1±38.8; p = 0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p = 0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)). Conclusions: Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant

Modeling the influence of changing storm patterns on the ability of a salt marsh to keep pace with sea level rise

Previous predictions on the ability of coastal salt marshes to adapt to future sea level rise (SLR) neglect the influence of changing storm activity that is expected in many regions of the world due to climate change. We present a new modeling approach to quantify this influence on the ability of salt marshes to survive projected SLR, namely, we investigate the separate influence of storm frequency and storm intensity. The model is applied to a salt marsh on the German island of Sylt and is run for a simulation period from 2010 to 2100 for a total of 13 storm scenarios and 48 SLR scenarios. The critical SLR rate for marsh survival, being the maximum rate at which the salt marsh survives until 2100, lies between 19 and 22 mm yr‐1. Model results indicate that an increase in storminess can increase the ability of the salt marsh to accrete with sea level rise by up to 3 mm yr‐1, if the increase in storminess is triggered by an increase in the number of storm events (storm frequency). Meanwhile, increasing storminess, triggered by an increase in the mean storm strength (storm intensity), is shown to increase the critical SLR rate for which the marsh survives until 2100 by up to 1 mm yr‐1 only. On the basis of our results, we suggest that the relative importance of storm intensity and storm frequency for marsh survival strongly depends on the availability of erodible fine‐grained material in the tidal area adjacent to the salt marsh