1,721,052 research outputs found
State-of-the-Art in Tissue-Engineered Heart Repair
No full textHeart muscle restoration with in vitro engineered tissue constructs is an exciting and rapidly advancing field. Feasibility, safety, and efficacy data have been obtained in animal models. First clinical trials are on the way to explore the therapeutic utility of cell-free and non-contractile cell-containing grafts. Engineering of contractile patches according to current good manufacturing practice (cGMP) for bona fide myocardial re-muscularization and scalability to address clinical demands remains challenging. Proof-of-concept for solutions to address obvious technical hurdles exists, and it can be anticipated that the first generation of clinically applicable engineered heart muscle (EHM) grafts will become available in the near future. Foreseeable, but likely manageable risks include arrhythmia induction and teratoma formation. Remaining biomedical challenges pertain to the requirement of immune suppression and the strategic approach to optimize immune suppression without subjecting the target patient population to an unacceptable risk. This chapter summarizes the current state of tissue-engineered heart repair with a special emphasis on knowledge gained from in vitro and in vivo studies as well as issues pertaining to transplant immunology and cGMP process development
The Contribution of Psychotherapists to Patient Care in Multidisciplinary Heart Transplantation Care Teams
No full textAuswirkungen einer Therapie mit Mycophenolat Mofetil und Ganciclovir auf die Ausbildung einer Transplantatarteriosklerose im murinen Aortenallograft-Transplantationsmodell
Full text linkBackground Success of heart transplantation and long-term allograft survival up to today is markedly dependent on the development of transplant arteriosclerosis, the clinical manifestation of chronic allograft rejection and still one of the leading causes for morbidity and mortality after transplantation. In order to suppress episodes of acute transplant rejection, Mycophenolate Mofetil (MMF), an inhibitor of inosinemonophosphate-dehydrogenase, has by now become an important part of modern immunosuppression regimes after heart transplantation. Immunosuppressive therapy frequently leads to an increased accessibility to opportunistic bacterial and viral infections. Above all, infections with Human Cytomegalovirus (HCMV) are very common in heart transplanted patients, as HCMV can be transmitted either in the course of transplantation, by postoperative, exogenous primary infection or by endogenous reactivation of virus latency in HCMV-seropositive transplant recipients during immunosuppression. Therefore, affected patients additionally receive anti-viral medication with ganciclovir. Potential synergistic effects of a combination therapy with MMF and ganciclovir with regards to the development of transplant arteriosclerosis, the number of CD4+ CD25+ FoxP3+ regulatory T cells(Tregs) and the expression of donor-specific alloantibodies were to be investigated in this study. Methods CBA.J (H2k) mice received an aortic graft of fully MHC-mismatched C57BL/6 (H2b) donors. Six groups of transplanted mice were administered MMF 100 or 300 mg/kg/d p.o., ganciclovir 10 or 72 mg/kg/d i.p., or a combination of MMF + ganciclovir. Examination of the grafts by histology and morphometry was performed on day 30 after transplantation. In addition, FACS analyses of splenic tissue were conducted to investigate effects of a MMF/ganciclovir-combination therapy on the number of Tregs. Levels of donor-specific alloantibodies were determined by FACS-analyses of peripheral blood. Results In our experiments MMF at a dose of 300 mg/kg/d led to a significant reduction of transplant arteriosclerosis and alloantibody-levels compared to untreated controls. So did the combinations of MMF 100 mg/kg/d + ganciclovir 10 mg/kg/d and of MMF 300 mg/kg/d + ganciclovir 72 mg/kg/d. On the other hand, monotherapy regimes with MMF at a dosage of 100 mg/kg/d or ganciclovir at 10 mg/kg/d or 72 mg/kg/d did not reveal significant effects on transplant arteriosclerosis or alloantibodies. In addition, FACS-analyses of splenic tissue did not reveal significant differences in CD4+ CD25+ FoxP3+ Treg counts between the respective experimental groups and untreated controls. Conclusions Combined therapy with MMF and ganciclovir exerts an inhibitory effect on the formation of transplant arteriosclerosis. Beyond MMFs well-established effects on cellular immune-response and smooth muscle proliferation, a decrease in alloantibody-production has most probably contributed to a reduction of transplant arteriosclerosis in our experimental model. However, there was no significant correlation between levels of transplant arteriosclerosis and Treg counts in our experimental groups.Hintergrund und Ziele Der langfristige Erfolg von Herztransplantationen und damit das Langzeitüberleben des Transplantats wird bis heute maßgeblich durch das Auftreten einer chronischen Transplantatabstoßungsreaktion in Form einer Transplant-Arteriosklerose limitiert. Dagegen sind akute Abstoßungsreaktionen durch moderne Immunsuppressiva effektiv zu behandeln. So ist auch Mycophenolat Mofetil (MMF), ein Inhibitor der Inosinmonophosphat-Dehydrogenase ein wichtiger Bestandteil in der immunsuppressiven Therapie zur Unterdrückung akuter Abstoßungsreaktionen nach Herztransplantationen. Als häufige Nebenwirkung einer Immunsuppressionstherapie entwickelt ein Teil der behandelten Patienten eine erhöhte Anfälligkeit für bakterielle wie auch virale Infektionen. Insbesondere kommt es häufig zu einer Infektion mit Humanem Cytomegalievirus (HCMV), entweder durch Übertragung vom Organspender auf den Empfänger im Rahmen der Organtransplantation, durch eine postoperative, exogene Primärinfektion, oder durch die endogene Reaktivierung einer latent persistierenden Infektion bei HCMV-seropositiven Transplantatempfängern. Klinisch begegnet man einer HCMV-Infektion durch Hemmung der viralen DNA-Synthese mit dem Virostatikum Ganciclovir. Das Ziel der vorliegenden Studie war die Untersuchung potentieller synergistischer Effekte einer Kombinationstherapie aus MMF und Ganciclovir auf die Transplantat-Arteriosklerose-Entwicklung, die Zahl CD4+ CD25+ FoxP3+ regulatorischer T-Zellen (Tregs) und die Expression Donor-spezifischer Alloantikörper. Methoden Vollständig MHC-inkompatible C57BL/6 (H2b)-Spenderaorten wurden in CBA.J (H2k)-Empfänger transplantiert. Sechs Gruppen transplantierter Tiere erhielten im Anschluss daran oral (p.o.) MMF in einer Dosis von 100 bzw. 300 mg/kg/d, intraperitoneal injiziertes (i.p.) Ganciclovir in einer 10 mg/kg/d- bzw. 72 mg/kg/d-Dosierung oder eine Kombination beider Medikamente in niedriger bzw. hoher Dosierung. Nach Entnahme der Transplantate an Tag 30 nach Implantation wurden diese histologisch und morphometrisch analysiert. Die Expression regulatorischer T-Zellen wurde mittels FACS-Analyse von Milzgewebe untersucht. Der quantitative Nachweis von Donor-spezifischen Alloantikörpern erfolgte ebenfalls mittels FACS-Analyse aus peripherem Blut. Ergebnisse und Beobachtungen Während sich bei der Behandlung mit MMF 100 mg/kg/d, Ganciclovir 10 mg/kg/d und 72 mg/kg/d keine nennenswerten Auswirkungen auf Transplantat-Arteriosklerose oder Alloantikörper zeigten, wiesen die mit MMF 300 mg/kg/d oder einer niedrig- bzw. hochdosierten MMF/Ganciclovir-Kombination behandelten Tiere im Vergleich zur Kontrollgruppe sowohl eine signifikant verminderte Transplantat-Arteriosklerose-Entwicklung, als auch signifikant geringere Alloantikörper-Spiegel im Serum auf. In Hinblick auf die Expression regulatorischer T-Zellen zeigten sich im analysierten Milzgewebe keine signifikanten Unterschiede zwischen den einzelnen Versuchsgruppen im Vergleich zur unbehandelten Kontrollgruppe. Praktische Schlussfolgerungen Unsere Ergebnisse belegen einen hemmenden Einfluss einer Kombinationstherapie aus MMF und Ganciclovir auf die Entwicklung einer Transplantat-Arteriosklerose. Neben den bereits bekannten Effekten von MMF auf die zelluläre Immunabwehr und die Proliferation glatter Gefäßmuskelzellen, scheint die Transplantat-Arteriosklerose-Reduktion in unserem Modell in erster Linie das Ergebnis einer verminderten Produktion Donor-spezifischer Alloantikörper zu sein. Signifikante Zusammenhänge zwischen Ausprägungsgrad der Transplantat-Arteriosklerose und Treg-Zahl konnten dagegen im vorliegenden experimentellen Modell nicht nachgewiesen werden
Funktionelle Untersuchung einer Missense-Variante im Matrix-Metalloproteinase-10 (MMP10) Gen in zwei Familien mit vorzeitigem Myokardinfarkt
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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