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    ABSTRACT: Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of drugs developed for treating type-2 diabetes mellitus. Patients with diabetes carry an up to 5-fold greater mortality risk compared to non-diabetic patients, mainly as a result of cardiovascular diseases. Although beneficial cardiovascular effects have been reported, exact mechanisms of GLP-1R-agonist action in the heart, especially in human myocardium, are poorly understood. The effects of GLP-1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac contractility were tested in non-failing atrial and ventricular trabeculae from 72 patients. The GLP-1(7-36)NH2 metabolite, GLP-1(9-36)NH2, was also examined. In electrically stimulated trabeculae, the effects of compounds on isometric force were measured in the absence and presence of pharmacological inhibitors of signal transduction pathways. The role of β-arrestin signaling was examined using a β-arrestin partial agonist, PF-06446667. Expression levels were tested by immunoblots. Translocation of GLP-1R downstream molecular targets, Epac2, GLUT-1 and GLUT-4, were assessed by fluorescence microscopy. All tested GLP-1R-agonists significantly increased developed force in human atrial trabeculae, whereas GLP-1(9-36)NH2 had no effect. Exendin(9-39)NH2, a GLP-1R-antagonist, and H-89 blunted the inotropic effect of exenatide. In addition, exenatide increased PKA-dependent phosphorylation of phospholamban (PLB), GLUT-1 and Epac2 translocation, but not GLUT-4 translocation. Exenatide failed to enhance contractility in ventricular myocardium. Quantitative real-time PCR (qRT-PCR) revealed a significant higher GLP-1R expression in the atrium compared to ventricle. Exenatide increased contractility in a dose-dependent manner via GLP-1R/cAMP/PKA pathway and induced GLUT-1 and Epac2 translocation in human atrial myocardium, but had no effect in ventricular myocardium. Therapeutic use of GLP-1R-agonists may therefore impart beneficial effects on myocardial function and remodelling.
    No preview · Article · Oct 2015 · Journal of Molecular and Cellular Cardiology
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    ABSTRACT: Metastatic renal cell carcinoma is potentially a lethal disease with in some cases aggressive behavior. The given fact that the patterns of metastases from RCC are not clearly identified, which may involve some rare metastatic locations. We present a case of 58 years old male presented with painless left scrotal mass, which was discovered to be an intrascrotal metastases appeared 3 years after nephrectomy for ipsilateral renal cell carcinoma. We believe that the rarity of the metastatic site and the intriguing possible mechanism of spread make an interesting case for clinicians and could add more follow-up measures for patients treated from renal cell carcinoma.
    Full-text · Article · Oct 2015 · Urology Case Reports
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    ABSTRACT: Diffuse involvement of liver and spleen is frequently seen in brucellosis, suppurative abscesses caused by Brucella are less common but well described. With the increased availability of cross-sectional imaging techniques, reports have become more frequent. Four patients with hepatosplenic abscesses caused by Brucella spp. are described and included in a review of 115 previously published cases. Clinical characteristics and patterns on ultrasound (US) and computer tomography imaging were analyzed. Furthermore, the proportion of patients with brucellosis affected by suppurative hepatosplenic lesions was estimated. Hepatosplenic abscesses were seen in 1.2% of patients with brucellosis, which were mostly caused by Brucella melitensis. Imaging analysis revealed two main distinct patterns. Solitary abscesses involving liver more frequently than spleen, and showing characteristic central calcifications, characterize the first pattern. Multiple smaller abscesses, frequent spleen involvement, and absence of calcifications characterize the second pattern. Blood and aspirate cultures were frequently negative, however, the positivity rate increased over the past years. Indirect Coombs test was positive in 96%. Half of the patients were cured by antibiotic treatment; case fatality in this series was 1.9%. Hepatosplenic abscesses due to Brucella infections have characteristic imaging findings. Clinicians should be aware of these and the proactive use of cross-sectional imaging, particularly US, should be encouraged in endemic regions. © The American Society of Tropical Medicine and Hygiene.
    No preview · Article · Aug 2015 · The American journal of tropical medicine and hygiene


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  • Head of Institution
    Professor Karl Max Einhäupl
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Top publications last week by reads

Autophagy 01/2016; 12(1):1-222. DOI:10.1080/15548627.2015.1100356
521 Reads
JAMA Pediatrics 01/2016; DOI:10.1001/jamapediatrics.2015.4276
263 Reads

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