Circulating endothelial cells demonstrate an attenuation of endothelial damage by minimizing the extracorporeal circulation

ObjectiveDetachment of endothelial cells may represent serious injury of the endothelium after cardiopulmonary bypass. We investigated whether the extent of endothelial injury is related to the type of cardiopulmonary bypass system used (conventional or minimized) and determined circulating endothelial cells as well as von Willebrand factor and soluble thrombomodulin.MethodsTwenty patients scheduled for elective coronary bypass grafting were randomly assigned to either the minimal extracorporeal circulation system or the standard cardiopulmonary bypass. Ten healthy volunteers served as controls. Circulating endothelial cells per milliliter of full blood were perioperatively determined by immunomagnetic cell separation technique. Endothelial plasma markers were measured by enzyme-linked immunosorbent assay.ResultsPreoperative circulating endothelial cell numbers did not differ between the experimental groups, but were significantly higher than in the healthy controls (18.6 ± 5.6 vs 7.2 ± 3.8, P < .001). At 6 hours, circulating endothelial cell numbers increased significantly compared with baseline in both experimental groups and peaked at 12 hours after cardiopulmonary bypass initiation, each time with significantly lower values in the minimal extracorporeal circulation group (6 hours: 44.0 ± 9.9 vs 29.6 ± 9.8, P = .007; 12 hours: 48.1 ± 6.8 vs 31.8 ± 7.1, P < .001). Likewise, von Willebrand factor and soluble thrombomodulin postoperatively increased in both groups with a tendency toward lower levels in the minimal extracorporeal circulation group. Although circulating endothelial cells gradually declined, continually with lower numbers in the minimal extracorporeal circulation group, the endothelial plasma markers remained elevated during observation time.ConclusionsCirculating endothelial cells represent a novel marker of the intrinsic endothelial damage caused by cardiopulmonary bypass. Its analysis facilitates the evaluation of cardiopulmonary bypass modifications as the minimal extracorporeal circulation system could be proven to be less injurious to endothelium and myocardium

Indication for percutaneous aortic valve implantation

The incidence of valvular aortic stenosis has increased over the past decades due to improved life expectancy. Surgical aortic valve replacement is currently the only treatment option for severe symptomatic aortic stenosis that has been shown to improve survival. However, up to one third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to high comorbidities resulting in a higher operative mortality rate. In the past such patients could only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement with the goal of offering a therapeutic solution for patients who are unfit for surgical therapy. Currently there are two catheter-based treatment systems in clinical application (the Edwards SAPIEN aortic valve and the CoreValve ReValving System), utilizing either a balloon-expandable or a self-expanding stent platform, respectively

Polyethylenimine-mediated gene delivery into human bone marrow mesenchymal stem cells from patients

Transplantation of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for post-infarction left ventricular (LV) dysfunction. However, age-related functional decline of stem cells has restricted their clinical benefits after transplantation into the infarcted myocardium. The limitations imposed on patient cells could be addressed by genetic modification of stem cells. This study was designed to improve our understanding of genetic modification of human bone marrow derived mesenchymal stem cells (hMSCs) by polyethylenimine (PEI, branched with Mw 25 kD), one of non-viral vectors that show promise in stem cell genetic modification, in the context of cardiac regeneration for patients. We optimized the PEI-mediated reporter gene transfection into hMSCs, evaluated whether transfection efficiency is associated with gender or age of the cell donors, analysed the influence of cell cycle on transfection and investigated the transfer of therapeutic vascular endothelial growth factor gene (VEGF). hMSCs were isolated from patients with cardiovascular disease aged from 41 to 85 years. Optimization of gene delivery to hMSCs was carried out based on the particle size of the PEI/DNA complexes, N/P ratio of complexes, DNA dosage and cell viability. The highest efficiency with the cell viability near 60% was achieved at N/P ratio 2 and 6.0 μg DNA/cm 2. The average transfection efficiency for all tested samples, middle-age group (&lt;65 years), old-age group (&gt;65 years), female group and male group was 4.32%, 3.85%, 4.52%, 4.14% and 4.38%, respectively. The transfection efficiency did not show any correlation either with the age or the gender of the donors. Statistically, there were two subpopulations in the donors; and transfection efficiency in each subpopulation was linearly related to the cell percentage in S phase. No significant phenotypic differences were observed between these two subpopulations. Furthermore, PEI-mediated therapeutic gene VEGF transfer could significantly enhance the expression level.DFG/SFB/Transregio 37BMBF/0313191German Helmholtz AssociationDFG/0402710Ministry of Education/0312138 AMinistry of Economy (Mecklenburg-West Pommerania)/V220-630-08-TFMVF/S-035Marie Curie International Research Staff Exchange Scheme (IRSES, FP7-PEOPLE-2009-IRSES)Reference and Translation Center for Cardiac Stem Cell Therapy (RTC

Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity

In this study, we characterize age-related phenotypes of human hematopoietic stem cells (HSC). We report increased frequencies of HSC, hematopoietic progenitor cells and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSC further exhibited a delay in initiating division ex vivo though without changes in their division kinetics. The activity of the small RhoGTPase Cdc42 was elevated in aged human hematopoietic cells and we identified a positive correlation between Cdc42 activity and the frequency of HSC upon aging. The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarization of aged human HSC with respect to Cdc42. Elevated activity of Cdc42 in aged HSC thus contributed to age-related changes in HSC. Xenotransplant, using NBSGW mice as recipients, showed elevated chimerism in recipients of aged compared to young HSC. Aged HSC treated with CASIN ex vivo displayed an engraftment profile similar to recipients of young HSC. Taken together, our work reveals strong evidence for a role of elevated Cdc42 activity in driving aging of human HSC, and similar to mice, this presents a likely possibility for attenuation of aging in human HSC

Sex-related Differences among Patients Undergoing Surgical Aortic Valve Replacement - A Propensity Score Matched Study.

OBJECTIVES We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). METHODS Data from two prospective registries, INDURE and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. RESULTS Females had a lower body mass index (BMI; median 27.1 vs 28.0 kg/m2; p = 0.008), fewer bicuspid valves (52% vs 59%; p = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; p < 0.001) and STS score (mean 1.6 vs 0.9%; p < 0.001), were more often in NYHA class III/IV (47% vs 30%; p < 0.001) and angina CCS III/IV (8.2% vs 4.4%; p < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; p = 0.028) compared to males. These differences vanished after PSM, except for EuroSCORE II and STS scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, p < 0.001). There were no differences in the length of hospital stay (median 8 days) or ICU stay (median 24 vs 25 hours) between both sexes. At two years, post-SAVR outcomes were comparable between males and females, even after PSM. CONCLUSIONS Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females

Finanzmärkte, Unternehmungen, Informationen: Ergebnisse des Projektes im Wintersemester 2015/2016

Der vorliegende Beitrag der Wirtschaftswissenschaftlichen Schriften ist ein Sammelband, der die Beiträge der Studierenden des 2. Fachsemesters im Masterstudiengang General Management aus dem Wintersemester 2015/2016 umfasst. Die Einzelbeiträge wurden in einer zwei Monate dauernden Projektarbeit im Herbst 2015 erarbeitet und im Januar 2016 präsentiert. Der diesjährige Themenschwerpunkt lag auf dem Bereich "Banken", jedoch fanden auch andere Bereiche Eingang in das Spektrum der Arbeiten. Das Besondere dieser Ausarbeitungen liegt darin, dass sie in Form eines journalistischen Artikels aufgebaut sind und die Autoren die Aufgabe hatten, eine auch für Nichtfachleute geeignete Form der Darstellung zu finden. Besonderer Wert wurde auch auf einen gut lesbaren Schreibstil und die Vielfalt der Gestaltungsformen gelegt. Die Arbeiten liegen hier in der Originalversion vor und wurden nicht redigiert. Die Fakten wurden nach bestem Wissen ermittelt, jedoch besteht kein Anspruch auf Vollständigkeit

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

A large outbreak of acute muscular sarcocystosis (AMS) among international tourists who visited Tioman Island, Malaysia, is described. Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS in their differential diagnosi

A novel pulsatile blood pump design for cardiothoracic surgery - proof-of-concept in a mock circulation

Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. We investigated the properties of a novel positive displacement blood pump in a mock circulation containing an aortic model with a human-like geometry and compliance as a pseudo patient. Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mmHg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mmHg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F=40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mmHg and F=40 bpm. At F=40 bpm, PP was 58.7 mmHg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings. The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications will help to establish this concept for adult pulsatile perfusion

Preservation of adrenoceptor and endothelin receptor mediated vasoconstriction after cold storage of explanted blood vessels for ex-vivo analyses

Purpose: Cold storage of blood vessels is a concern in bypass surgery and in ex vivo pharmacological experiments. We compared adrenoceptor and endothelin receptor-mediated vasoconstriction as well as endothelium-dependent vasodilation before and after 20 h storage in commercial and custom-made vessel storage solutions. Methods: Saphenous veins harvested during coronary artery bypass surgery were analyzed by isometric force measurements in organ baths before and after cold storage for 20 h in HEPES-supplemented Dulbecco's modified Eagle's medium (HDMEM), HEPES-supplemented Krebs-Henseleit solution (HKH), or TiProtec solution. Contractile responses to potassium chloride (KCl), norepinephrine (NE), and endothelin-1 (ET-1) as well as vasodilator responses to acetylcholine (ACh) were evaluated. Results: Storage in HDMEM diminished KCl induced contractile forces to 71% (p=0.002) and NE induced contractions to 80% (p=0.037) with no significant changes with the other solutions. NE induced contractions normalized to KCl were not affected by storage. NE EC50 values were slightly lower (7.1E-8 vs. 7.5E-8, p=0.019) after storage in HKH with no changes after storage in the other solutions. Endothelium-dependent responses to ACh were not affected by storage. ET-1 induced contractions were attenuated after storage in HDMEM (77%, p=0.002), HKH (75%, p=0.020), and TiProtec (73%, p=0.010) with no changes in the KCl-normalized constrictions. ET-1 EC50 values were not affected by storage. Conclusion: Changes in contractility after storage likely reflect malnutrition during cold storage with no specific attenuation of adrenoceptor or endothelin-receptor mediated signal transduction. HKH or TiProtec are equally suitable cold storage solutions for preserving blood vessel function for ex-vivo measurements

Hemodynamic energy during pulsatile extracorporeal circulation using flexible and rigid arterial tubing: a reassessment

Introduction: Pulsatile extracorporeal circulation may improve organ perfusion during cardiac surgery. Some minimally invasive extracorporeal circulation (MiECC) systems allow pulsatile perfusion. The present study investigated the influence of arterial tubing compliance on hemodynamic energy transfer into the patient. Methods: Aortic models with adult human geometry were perfused in a mock circulation. A MiECC system was connected using either high-compliance silicone tubing or standard kit tubing. Energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) were computed from flow and pressure data. Aortic models with physiological and sub-physiological compliance were tested to assess the influence of the pseudo-patient. Results: Non-pulsatile flow did not generate SHE. SHE during pulsatile flow in the compliant aortic model was significantly higher with kit tubing compared to silicone tubing. Maximum SHE was achieved at 1.6 L/min with kit tubing (7.7% of mean arterial pressure) and with silicone tubing (4.9%). Using the low-compliance aortic model, SHE with kit tubing reached a higher maximum of 14.2% at 1.8 L/min compared to silicone tubing (11.8% at 1.5 L/min). Conclusions: Flexible arterial tubing did not preserve more hemodynamic energy from a pulsatile pump compared to standard kit tubing in a model of adult extracorporeal circulation. The pseudo-patient’s compliance significantly affected the properties of the mock circulation. © In Copyright http://rightsstatements.org/vocab/InC/1.0