Isolierung und Charakterisierung von adulten Pankreasstammzellen zur endokrinen Differenzierung in Richtung Insulin produzierender Zellen

Mit dieser Arbeit ist es uns gelungen, Pdx-1-exprimierende adulte murine Pankreasstammzellen zu isolieren, die wichtige, in der Literatur beschriebene Stammzellmarker aufweisen. Außerdem ist es uns gelungen, mit Hilfe sogenannter "small molecules" wichtige proendokrine Faktoren wie MafA und Ngn3 zu beeinflussen

Association of prehospital acetylsalicylic acid and heparin administration with favorable neurological outcome after out-of-hospital cardiac arrest: a matched cohort analysis of the German Resuscitation Registry

Purpose!#!To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates.!##!Methods!#!Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes.!##!Results!#!Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame).!##!Conclusions!#!Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance

Attenuation of cardiac hypertrophy by G-CSF is associated with enhanced migration of bone marrow-derived cells

Granulocyte-colony stimulating factor (G-CSF) has been shown to promote mobilization of bone marrow-derived stem cells (BMCs) into the bloodstream associated with improved survival and cardiac function after myocardial infarction. Therefore, the aim of the present study was to investigate whether G-CSF is able to attenuate cardiac remodelling in a mouse model of pressure-induced LV hypertrophy focusing on mobilization and migration of BMCs. LV hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6J mice. Fourweeks after TAC procedure. Mice were treated with G-CSF (100g/kg/day;Amgen Biologicals) for 2weeks. The number of migrated BMCs in the heart was analysed by flow cytometry. mRNA expression and protein level of different growth factors in the myocardium were investigated by RT-PCR and ELISA. Functional analyses assessed by echocardiography and immunohistochemical analysis were performed 8weeks after TAC procedure. G-CSF-treated animals revealed enhanced homing of VLA-4(+) and c-kit(+) BMCs associated with increased mRNA expression and protein level of the corresponding homing factors Vascular cell adhesion protein 1 and Stem cell factor in the hypertrophic myocardium. Functionally, G-CSF significantly preserved LV function after TAC procedure, which was associated with a significantly reduced area of fibrosis compared to control animals. Furthermore, G-CSF-treated animals revealed a significant improvement of survival after TAC procedure. In summary, G-CSF treatment preserves cardiac function and is able to diminish cardiac fibrosis after induction of LV hypertrophy associated with increased homing of VLA-4(+) and c-kit(+) BMCs and enhanced expression of their respective homing factors VCAM-1 and SCF

Lower frequency routine surveillance endomyocardial biopsies after heart transplantation

In heart transplantation (HTx) patients, routine surveillance endomyocardial biopsies (rsEMB) are recommended for the detection of early cardiac allograft rejection. However, there is no consensus on the optimal frequency of rsEMB. Frequent rsEMB have shown a low diagnostic yield in the new era of potent immunosuppressive regimen. Efficacy and safety of lower frequency rsEMB have not been investigated so far. In this retrospective, single centre, observational study we evaluated 282 patients transplanted between 2004 and 2014. 218 of these patients were investigated by rsEMB and symptom-triggered EMB (stEMB). We evaluated EMB results, complications, risk factors for rejection, survival 1 and 5 years as well as incidence of cardiac allograft vasculopathy (CAV) 3 years after HTx. A mean of 7.1 +/- 2.5 rsEMB were conducted per patient within the first year after HTx identifying 7 patients with asymptomatic and 9 patients with symptomatic acute rejection requiring glucocorticoide pulse therapy. Despite this relatively low frequency of rsEMB, only 6 unscheduled stEMB were required in the first year after HTx leading to 2 additional treatments. In 6 deaths among all 282 patients (2.1%), acute rejection could not be ruled out as a potential underlying cause. Overall survival at 1 year was 78.7% and 5-year survival was 74%. Incidence of CAV was 17% at 3-year follow-up. Morbidity and mortality of lower frequency rsEMB are comparable with data from the International Society for Heart and Lung Transplantation (ISHLT) registry. Consensus is needed on the optimal frequency of EMB

Midkine drives cardiac inflammation by promoting neutrophil trafficking and NETosis in myocarditis

Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Inhibition of NET formation in experimental autoimmune myocarditis (EAM) of mice substantially reduces inflammation in the acute phase of the disease. Targeting the cytokine midkine (MK), which mediates NET formation in vitro, not only attenuates NET formation in vivo and the infiltration of polymorphonuclear neutrophils (PMNs) but also reduces fibrosis and preserves systolic function during EAM. Low-density lipoprotein receptor-related protein 1 (LRP1) acts as the functionally relevant receptor for MK-induced PMN recruitment as well as NET formation. In summary, NETosis substantially contributes to the pathogenesis of myocarditis and drives cardiac inflammation, probably via MK, which promotes PMN trafficking and NETosis. Thus, MK as well as NETs may represent novel therapeutic targets for the treatment of cardiac inflammation

ELISA

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