First, the quartz glass substrate (Suprasil, Heraeus) is covered with a 70 nm thick spacer layer by spin-coating. A solidifiable photopolymer, PC403 (JCR, Japan), is used. A prebaking process is first carried out to remove the solvent from the polymer (increase of the baking temperature from 90 °C to 130 °C). A sufficiently long bake at a higher temperature (30 min at 180 °C) further hardens the layer. Next the three particle L-shape layer (dot diameter 200 nm, surface-to-surface distance 20 nm) and alignment markers are defined in resist (double layer PMMA, Allresist) using electron-beam lithography (Raith e_Line). The substrate is then covered with a 2 nm Cr adhesion layer and a 40 nm gold film using thermal evaporation followed by a lift-off procedure. Subsequently, a 70 nm thick spacer layer of PC403 is applied. Afterwards the substrate is coated once more with PMMA resist. Computercontrolled alignment at the sub-10 nm level using the gold alignment markers is applied to ensure the accurate positioning of the upper dot layer. Metal evaporation, lift off, and final planarization are repeated. All samples have a total area of 30 µm ×30 µm. All scanning electron microscope (SEM) images are taken with a Hitachi S-4800 scanning electron microscope. Optical characterisationThe spectra are measured using a Fourier-transform infrared spectrometer (Bruker Vertex 80, tungsten lamp), equipped with an infrared microscope (Bruker Hyperion). The incident light is focused with a Cassegrain objective with numerical aperture N = 0.4, and the transmitted intensities are detected with Si and InGaAs diodes. The incident polarization is set with an infrared polarizer and a broadband (700 nm -2500 nm) infrared quarterwaveplate (B. Halle Nachfl., Berlin). The measured spectra are normalized with respect to the substrate.

Summary A rare eosinophilic dermatosis, Wells syndrome, also referred to as eosinophilic cellulitis, is characterized by great clinical variability. Typical findings include infiltrated erythematous plaques arising on the extremities. Lesions initially resemble erysipelas/cellulitis, however, they do not improve with antibiotic treatment. Eosinophilic cellulitis is a diagnosis of exclusion that may only be made over the course of the disease, taking into account clinical and characteristic histological findings (flame figures). Although multiple potential triggers have been proposed, the exact etiology remains unresolved. Involvement of abnormal Th2 cells, IL‐5, and activated eosinophilic granulocytes suggest a nonspecific hypersensitivity response to exogenous or endogenous stimuli. Corticosteroids may have a beneficial effect on the chronic, recurrent course frequently observed. The disease is often self‐limiting, healing without sequelae. Given that transitions to hematological and oncological disorders have been observed, patients should be closely followed up.

For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 micrograms PGE1 or placebo 5 days a week for 4 weeks. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication.

Tight regulation of cytokines is essential for the initiation and resolution of inflammation. Chemerin, a mediator of innate immunity, mainly acts on chemokine-like receptor 1 (CMKLR1) to induce the migration of macrophages and dendritic cells. The role of the second chemerin receptor, G protein-coupled receptor 1 (GPR1), is still unclear. Here we demonstrate that GPR1 shows ligand-induced arrestin3 recruitment and internalization. The chemerin C-terminus triggers this activation by folding into a loop structure, binding to aromatic residues in the extracellular loops of GPR1. While this overall binding mode is shared between GPR1 and CMKLR1, differences in their respective extracellular loop 2 allowed for the design of the first GPR1-selective peptide. However, our results suggest that ligand-induced arrestin recruitment is not the only mode of action of GPR1. This receptor also displays constitutive internalization, which allows GPR1 to internalize inactive peptides efficiently by an activation-independent pathway. Our results demonstrate that GPR1 takes a dual role in regulating chemerin activity: as a signaling receptor for arrestin-based signaling on one hand, and as a scavenging receptor with broader ligand specificity on the other. Graphic abstract

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