Sklerodermie

Zusammenfassung: Die Sklerodermie (Synonyme: systemische Sklerose, systemische Sklerodermie) ist eine Systemerkrankung, die neben der Haut auch innere Organe wie die Lunge, den Gastrointestinaltrakt, die Niere und das Herz befällt. Pathogenetisch ist zwischen einer unkontrollierten Bindegewebsvermehrung (Fibrose) und einer Vaskulopathie zu unterscheiden. Dies führt klinisch neben den Organfibrosen auch zu Gefäßmanifestationen. Hierzu zählen Fingerkuppenulzera, die pulmonalarterielle Hypertonie und die akute Nierenkrise. Von der systemischen Sklerose sind lokalisierte Sklerodermieformen wie die Morphea abzugrenzen, die ohne Organkomplikationen verlaufen. Aufgrund ihrer klinischen Heterogenität, ihrer hohen Morbidität und Mortalität stellt die systemischen Sklerose für den klinischen Alltag eine große diagnostische und therapeutische Herausforderung dar. Dieser Übersichtsartikel fasst den aktuellen Stand zur Klassifikation und Epidemiologie, Pathogenese, den wichtigsten klinischen Manifestationen wie interstitielle Fibrose, pulmonalarterielle Hypertonie, akute Nierenkrise und periphere Vaskulopathie zusammen und gibt einen Überblick aktueller und zukünftiger Therapiemöglichkeite

Systemische Sklerose: Zielkriterien der Behandlung

Zusammenfassung: Die systemische Sklerose (SSc) ist eine Multisystemfibrose mit weltweitem Vorkommen und hoher Morbidität und Mortalität. Charakteristika der Erkrankung sind ausgedehnte Vaskulopathie, Entzündung, Autoimmunität und Fibrose. Therapieerfolge der letzten Jahre beinhalten im Wesentlichen ein besseres Management von Organkomplikationen. Bis heute gibt es jedoch keine zugelassene spezifische Therapie, die das Fortschreiten der Erkrankung verhindern oder auch nur verlangsamen kann. Konventionelle DMARDs ("disease-modifying antirheumatic drugs") haben keinen substanziellen Einfluss auf den Erkrankungsverlauf und verlängern das Gesamtüberleben nicht. Aufgrund molekularbiologischer Studien und verschiedener Tiermodelle konnten in den letzten Jahren Schlüsselmoleküle der Pathogenese von Fibrose und Vaskulopathie in SSc identifiziert werden. Vor diesem Hintergrund müssen nun Zielkriterien der Behandlung neu überdacht und definiert werden. In diesem Artikel werden mit Bezug auf pulmonal-arterielle Hypertonie, Lungenfibrose und Haut-/Systemfibrose aktuelle und künftige Therapiekonzepte, Ziele der Behandlung und Erfassung/Bewertung von Verlaufsparametern diskutier

Surface-wave interferometry on single subwavelength slit-groove structures fabricated on gold films

We apply the technique of far-field interferometry to measure the properties of surface waves generated by two-dimensional (2D) single subwavelength slit-groove structures on gold films. The effective surface index of refraction measured for the surface wave propagating over a distance of more than 12 microns is determined to be 1.016 with a measurement uncertainty of 0.004, to within experimental uncertainty of the expected bound surface plasmon-polariton (SPP) value for a Au/Air interface of 1.018. We compare these measurements to finite-difference-time-domain (FDTD) numerical simulations of the optical field transmission through these devices. We find excellent agreement between the measurements and the simulations for the surface index of refraction. The measurements also show that the surface wave propagation parameter exhibits transient behavior close to the slit, evolving smoothly from greater values asymptotically toward the value expected for the SPP over the first 2-3 microns of slit-groove distance. This behavior is confirmed by the FDTD simulations

Modelling alternative strategies for delivering hepatitis B vaccine in prisons : the impact on the vaccination coverage of the injecting drug user population

Since 2001 hepatitis B vaccination has been offered to prisoners on reception into prisons in England and Wales. However, short campaigns of vaccinating the entire population of individual prisons have achieved high vaccination coverage for limited periods, suggesting that short campaigns may be a preferable way of vaccinating prisoners. A model is used that describes the flow of prisoners through prisons stratified by injecting status to compare a range of vaccination scenarios that describe vaccination on prison reception or via regular short campaigns. Model results suggest that vaccinating on prison reception can capture a greater proportion of the injecting drug user (IDU) population than the comparable campaign scenarios (63% vs. 55 . 6% respectively). Vaccination on prison reception is also more efficient at capturing IDUs for vaccination than vaccination via a campaign, although vaccination via campaigns may have a role with some infections for overall control

Synovial fibroblasts: key players in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and ultimately leads to their destruction. The involvement of immune cells is a general hallmark of autoimmune-related disorders. In this regard, macrophages, T cells and their respective cytokines play a pivotal role in RA. However, the notion that RA is a primarily T-cell-dependent disease has been strongly challenged during recent years. Rather, it has been understood that resident, fibroblast-like cells contribute significantly to the perpetuation of disease, and that they may even play a role in its initiation. These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. A number of studies have demonstrated that RASFs show alterations in morphology and behaviour, including molecular changes in signalling cascades, apoptosis responses and in the expression of adhesion molecules as well as matrix-degrading enzymes. These changes appear to reflect a stable activation of RASFs, which occurs independently of continuous exogenous stimulation. As a consequence, RASFs are no longer considered passive bystanders but active players in the complex intercellular network of R

The Significance of Porfolio Lenders to Real Estate Brokers

For the reasons observed in the sample of mortgage loans examined, the real estate brokerage industry will continue to depend heavily on portfolio lending to finance residential housing transactions. This paper examines a sample of residential mortgages to determine the breadth of lending by home type and customer credit qualification. The findings show that portfolio lending is required to satisfy homebuyers with heterogenous mortgage loan needs. Comparative analysis of credit decisions provides evidence of sound lending.

IL-15 and its role in rheumatoid arthritis

Background: IL-15 is involved in all phases of rheumatoid arthritis. Recently we have shown that rheumatoid arthritis synovial fibroblasts (RASF) express both IL-15 and functional IL-15 receptor [1]. Objective: The aim of present study was to identify pathways that are regulated by autocrine IL-15 (IL-15R) in RASF. Methods: RASF were transfected with plasmid encoding IL-15R antagonist (CRB-15, Cardion AG) or control constructs. RNA from transient transfectants were used for Microarray analysis. The differential expression of genes obtained by microarray analysis was verified by SYBR Green real-time PCR. The expression of IL-15Rα, cell proliferation and the expression of p16 and p21 were evaluated in stably transfected cells. Results: The IL-15R antagonist produced by transfected RASF blocked the endogenous IL-15/IL-15Rα interaction, which resulted in an inhibition of cell proliferation (45 ± 10%) via an increase of the expression of p16. In addition, we found that inhibition of IL-15Rα induced the expression of mRNA for FGFR-3. Since two isoforms of FGFR-3 have been identified (FGFR-3b and FGFR-3c) [2], we tested the effect of IL-15Rα inhibition on their expression. In contrast to FGFR-3b, the level of mRNA for FGFR-3c was strongly increased in cells transfected with the IL-15R antagonist (4.71 ± 2.5 in transient transfectants and 6.1 ± 1 fold in stable transfectants). FGFR-3c isoform binds specifically FGF-9, but also FGF-2 [2]. Besides FGFR-3, FGF-2 that is abundant in RA joints binds to FGFR-1. In vitro studies revealed that FGFR-1 transmits a potent mitogenic signal, whereas FGFR-3 usually has no stimulatory effect or inhibits cell proliferation. In contrast to FGFR-3c, blocking of IL-15Rα did not change the mRNA expression for FGFR-1 in RASF. Moreover, we checked whether FGF-2 affects the expression of IL-15Rα. Indeed, FGF-2 strongly decreased the spontaneous and tumor necrosis factor alpha-triggered expression of IL-15Rα at the mRNA and protein levels. Conclusion: Our findings raise the possibility of a negative loop between FGF-2/FGFR-3c and IL-15/IL-15R signaling in RASF. Moreover, the activation of RASF by FGFs could depend on the ratio of FGFR-1/FGFR-3 expression, which is controlled by the endogenous IL-15/IL-15R system

Surface wave generation and propagation on metallic subwavelength structures measured by far-field interferometry

Transmission spectra of metallic films or membranes perforated by arrays of subwavelength slits or holes have been widely interpreted as resonance absorption by surface plasmon polaritons (SPPs). Alternative interpretations involving evanescent waves diffracted on the surface have also been proposed. These two approaches lead to divergent predictions for some surface wave properties. Using far-field interferometry, we have carried out a series of measurements on elementary one-dimensional (1-D) subwavelength structures with the aim of testing key properties of the surface waves and comparing them to predictions of these two points of view