Gene Deletion of the Kinin Receptor B1 Attenuates Cardiac Inflammation and Fibrosis During the Development of Experimental Diabetic Cardiomyopathy

Objective: Diabetic cardiomyopathy is associated with increased mortality in patients with diabetes mellitus. The underlying pathology of this disease is still under discussion. We studied the role of the kinin B1 receptor on the development of experimental diabetic cardiomyopathy. Research Design and Methods: We utilized B1 receptor knockout mice and investiged cardiac inflammation, fibrosis and oxidative stress after induction of streptozotocin (STZ)-induced diabetes mellitus. Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes mellitus. Results: B1 receptor knockout mice showed an attenuation of diabetic cardiomyopathy with improved systolic and diastolic function in comparison with diabetic control mice. This was associated with a decreased activation state of the MAP kinase p38, less oxidative stress as well as normalized cardiac inflammation, shown by fewer invading cells and, no increase in matrix metalloproteinase-9 as well as the chemokine CXCL-5. Furthermore, the pro-fibrotic connective tissue growth factor was normalized, leading to a reduction in cardiac fibrosis despite severe hyperglycemia in mice lacking the B1 receptor. Conclusion: These findings suggest that the B1 receptor is detrimental in diabetic cardiomyopathy in that it mediates inflammatory and fibrotic processes. These insights might have useful implications on future studies utilizing B1 receptor antagonists for treatment of human diabetic cardiomyopathy

PORTAL: Pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection: a double-blind randomized placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Major surgical procedures facilitate systemic endotoxinemia and formation of free radicals with subsequent inflammatory changes that can influence the postoperative course. Experimental data suggest that preoperative supraphysiological doses of melatonin, a potent immuno-modulator and antioxidant, would decrease postoperative infectious and non-infectious complications induced by major abdominal surgery.</p> <p>Methods/Design</p> <p>A randomized controlled double blind single center clinical trial with two study arms comprising a total of 40 patients has been designed to assess the effects of a single preoperative dose of melatonin before major liver resection. Primary endpoints include the determination of safety and tolerance of the regimen as well as clinical parameters reflecting pathophysiological functions of the liver. Furthermore, data on clinical outcome (infectious and non-infectious complications) will be collected as secondary endpoints to allow a power calculation for a randomized clinical trial aiming at clinical efficacy.</p> <p>Discussion</p> <p>Based on experimental data, this ongoing clinical trial represents an advanced element of the research chain from bench to bedside in order to reach the highest level of evidence-based clinical facts to determine if melatonin can improve the general outcome after liver resection.</p> <p>Trial Registration</p> <p>EudraCT200600530815</p

Transaction-Based Pseudonyms in Audit Data for Privacy Respecting Intrusion Detection

Abstract. Privacy and surveillance by intrusion detection are poten-tially conflicting organizational and legal requirements. In order to sup-port a balanced solution, audit data is inspected for personal data and identifiers referring to real persons are substituted by transaction-based pseudonyms. These pseudonyms are constructed as shares for a suitably adapted version of Shamir’s cryptographic approach to secret sharing. Under sufficient suspicion, expressed as a threshold on shares, audit an-alyzers can perform reidentification

Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor

The clinical use of the anthracycline doxorubicin (Dox) is limited by its cardio toxic effects, which is attributed to the induction of apoptosis. To investigate the possible role of the B1 receptor during the development of Dox cardiomyopathy we studied B1 receptor knockout mice (B1(-/-)) by investigating cardiac inflammation and apoptosis after induction of DOX induced cardiomyopathy. DOX control mice showed cardiac dysfunction measured by pressure-volume loops in vivo. This was associated with a reduced activation state of AKT as well as an increased ratio of bax/bcl2 in western blots, as an indicator of cardiac apoptosis. Furthermore, the mRNA content of the pro inflammatory cytokine interleukin 6 was increased in the cardiac tissue. In Dox B1(-/-) cardiac dysfunction was improved compared to DOX control mice, which was associated with a normalization of the bax/bcl-2 ratio and interleukin 6 as well as AKT activation state. These findings suggest that the B1 receptor is detrimental in DOX cardiomyopathy in that it mediates inflammatory and apoptosis. These insights might have useful implications on future studies utilizing B1 receptor antagonists for treatment of human DOX cardiomyopathy

Excitation Spectrum and Superfluid Gap of an Ultracold Fermi Gas

Funding Information: We thank R. Haussmann, L. Mathey, C. Vale, and W. Zwerger for helpful discussions and R. Haussmann, W. Zwerger, and P. Pieri for providing us with the results of their calculations. This work is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) in the framework of SFB-925, Project No. 170620586, and the excellence cluster Advanced Imaging of Matter, EXC 2056, Project ID No. 390715994. Publisher Copyright: © 2022 American Physical Society.Ultracold atomic gases are a powerful tool to experimentally study strongly correlated quantum many-body systems. In particular, ultracold Fermi gases with tunable interactions have allowed to realize the famous BEC-BCS crossover from a Bose-Einstein condensate (BEC) of molecules to a Bardeen-Cooper-Schrieffer (BCS) superfluid of weakly bound Cooper pairs. However, large parts of the excitation spectrum of fermionic superfluids in the BEC-BCS crossover are still unexplored. In this work, we use Bragg spectroscopy to measure the full momentum-resolved low-energy excitation spectrum of strongly interacting ultracold Fermi gases. This enables us to directly observe the smooth transformation from a bosonic to a fermionic superfluid that takes place in the BEC-BCS crossover. We also use our spectra to determine the evolution of the superfluid gap and find excellent agreement with previous experiments and self-consistent T-matrix calculations both in the BEC and crossover regime. However, toward the BCS regime a calculation that includes the effects of particle-hole correlations shows better agreement with our data.Peer reviewe

SHEDEL - A Simple Hierarchical Event Description Language for Specifying Attack Signatures

Abstract: A main problem for the detection of security violations in misuse detection systems is the manner how attack scenarios (signatures) are described. Attack languages are used to specify attack scenarios for misuse detection systems. Usually not only the attack signatures are described also some details controlling the detection process have to be noted. This is disadvantageous because it makes signature development more complicated and prone to errors. In this paper we propose an attack language for describing signatures without caring about the used detection techniques. The language further provides means to simplify the description of attack signatures

Einfluss von Vitamin E auf degenerative Erkrankungen des Bewegungsapparates Abschlussbericht

SIGLETIB: AC 9895 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Host-orientiertes Netz-Audit

Available from TIB Hannover: RR 8073(1996,7) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman