Immunsuppressiva nach Transplantation: Dermatologische Relevanz und Pathomechanismen

Zusammenfassung: Immunsuppressiva verhindern nach Transplantation solider Organe einer Abstoßung. Auf der Haut treten dabei Medikamentenreaktionen, entzündliche Erkrankungen und Infektionen gehäuft auf. Spezifische Nebenwirkungen von Immunsuppressiva können durch Wechsel von Substanz oder Medikamentenklasse vermieden werden. Immunsuppressiva sind neben ultraviolettem Licht die treibende Kraft für das häufige Auftreten von spinozellulärem Karzinom der Haut bei Organtransplantation. Neben der reinen Immunsuppression fördert Ciclosporin die Krebsentstehung über TGF-β und VEGF, wirken mTOR-Inhibitoren antiproliferativ und kann Azathioprin auf UVA lichtsensibilisieren und direkten DNS-Schaden ermöglichen. Klinische Daten ermutigen bei spinozellulärem Karzinom der Haut sicher zur Reduktion der Immunsuppression überhaupt, wahrscheinlich zu einem Wechsel von Kalzineurininhibitoren auf mTOR-Inhibitoren und möglicherweise zu einem Absetzen von Azathiopri

Phototherapie und Karzinogenese

Zusammenfassung: Phototherapie nutzt mit Erfolg die kurzfristige antiproliferative und antientzündliche Wirkung von ultraviolettem Licht. Wegen seiner längerfristigen Wirkung jedoch ist ultraviolettes Licht als Karzinogen anerkannt. Die Wellenlängen der Phototherapie zeigen pathomechanistisch verschiedene karzinogene Wirkungen, zuvorderst Mutationen der Keratinozyten-DNS. Klinisch zeigt PUVA besonders nach 350Sitzungen auf Lebenszeit ein deutlich erhöhtes Risiko für spinozelluläre Karzinome der Haut. Melanom und genitaler Hautkrebs jedoch sind nicht durch alleinige PUVA erhöht. Vorbestehende UV-Belastung, Immunsuppression und weitere systemische Behandlung erhöhen die Karzinogenese durch PUVA. UVB-Breitband, -Schmalband ("narrow band") und UVA1 zeigen bisher keine klinische Erhöhung der Karzinogenese, müssen aber in ihren Spätfolgen weiter überwacht werden. Phototherapie ist weiterhin eine sichere Behandlungsmodalität, sofern die Indikation gut begründet ist, Vorbehandlungen sowie Begleitmedikation und -umstände berücksichtigt, eher kurze und dosisintensive Protokolle gewählt werden, PUVA als Zweitlinienbehandlung eingesetzt wird und 250 bis 300Sitzungen Phototherapie auf Lebenszeit nicht überschritten werde

Recurrence spectrum in smooth dynamical systems

We prove that for conformal expanding maps the return time does have constant multifractal spectrum. This is the counterpart of the result by Feng and Wu in the symbolic setting

Memory distribution in complex fitness landscapes

In a co-evolutionary context, the survive probability of individual elements of a system depends on their relation with their neighbors. The natural selection process depends on the whole population, which is determined by local events between individuals. Particular characteristics assigned to each individual, as larger memory, usually improve the individual fitness, but an agent possess also endogenous characteristics that induce to re-evaluate her fitness landscape and choose the best-suited kind of interaction, inducing a non absolute value of the outcomes of the interaction. In this work, a novel model with agents combining memory and rational choice is introduced, where individual choices in a complex fitness landscape induce changes in the distribution of the number of agents as a function of the time. In particular, the tail of this distribution is fat compared with distributions for agents interacting only with memory.Comment: 6 pages, 3 figures, submited to Physica

Phase transitions for rock-scissors-paper game on different networks

Monte Carlo simulations and dynamical mean-field approximations are performed to study the phase transitions in rock-scissors-paper game on different host networks. These graphs are originated from lattices by introducing quenched and annealed randomness simultaneously. In the resulting phase diagrams three different stationary states are identified for all structures. The comparison of results on different networks suggests that the value of clustering coefficient plays an irrelevant role in the emergence of a global oscillating phase. The critical behavior of phase transitions seems to be universal and can be described by the same exponents.Comment: 4 pages, 4 figures, to be published in PR

Segregation process and phase transition in cyclic predator-prey models with even number of species

We study a spatial cyclic predator-prey model with an even number of species (for n=4, 6, and 8) that allows the formation of two defective alliances consisting of the even and odd label species. The species are distributed on the sites of a square lattice. The evolution of spatial distribution is governed by iteration of two elementary processes on neighboring sites chosen randomly: if the sites are occupied by a predator-prey pair then the predator invades the prey's site; otherwise the species exchange their site with a probability $X$. For low $X$ values a self-organizing pattern is maintained by cyclic invasions. If $X$ exceeds a threshold value then two types of domains grow up that formed by the odd and even label species, respectively. Monte Carlo simulations indicate the blocking of this segregation process within a range of X for n=8.Comment: 5 pages, 5 figures, to be appear in Phys. Rev.

Replica Symmetry Breaking in the Random Replicant Model

We study the statistical mechanics of a model describing the coevolution of species interacting in a random way. We find that at high competition replica symmetry is broken. We solve the model in the approximation of one step replica symmetry breaking and we compare our findings with accurate numerical simulations.Comment: 12 pages, TeX, 5 postscript figures are avalaible upon request, submitted to Journal of Physics A: Mathematical and Genera

Anti-melanocortin-4 receptor autoantibodies in obesity

Background: The melanocortin-4 receptor (MC4R) is part of an important pathway regulating energy balance. Here we report the existence of autoantibodies (autoAbs) against the MC4R in sera of obese patients. Methods: The autoAbs were detected after screening of 216 patients' sera by using direct and inhibition ELISA with an N-terminal sequence of the MC4R. Binding to the native MC4R was evaluated by flow cytometry and pharmacological effects by measuring adenylyl cyclase activity. Results: Positive results in all tests were obtained in patients with overweight or obesity (prevalence: 3.6%) but not in normal weight patients. The selective binding properties of anti-MC4R autoAbs were confirmed by surface plasmon resonance and by immunoprecipitation with the native MC4R. Finally it was demonstrated that these autoAbs increased food intake in rats after passive transfer via intracerebroventricular injection. Conclusion: These observations suggest that inhibitory anti-MC4R autoAbs might contribute to the development of obesity in a small subpopulation of patients