Peritoneal dialysis is limited by morphologic changes of the peritoneal membrane. Use of peritoneal dialysis fluids (PDF) that contain glucose degradation products (GDP) generates advanced glycation end-products (AGE) within the peritoneal cavity. It is unknown whether peritoneal damage is causally related to AGE-receptor for AGE (RAGE) interaction. The effects of PDF were compared with different amounts of GDP on morphologic changes of the peritoneal membrane in 48 wild-type (WT) and 48 RAGE-deficient mice. PDF (1 ml) were instilled twice daily over a period of 12 wk. Groups with eight animals each received no manipulation ( Long-term PD is limited by structural and functional changes of the peritoneal membrane resulting in dialysis failure (1). Conventional PD fluids (PDF) are a source of glucose degradation products (GDP; carbonyl compounds) that are generated during heat sterilization under acidic conditions (2). Such GDP are highly reactive substances (2-10) that exhibit considerable direct cytotoxicity. However, GDP lead to the formation of advanced glycation end-products (AGE) (11). The extent to which peritoneal damage from GDP is due either to direct effects, e.g., illustrated by generation of vascular endothelial growth factor (VEGF) by methylglyoxal in peritoneal cells (12), or to indirect effects such as the generation of AGE from precursor GDP is unknown. To investigate mechanisms of AGE-dependent peritoneal damaging, we compared PDF with different GDP contents in wild-type (WT) and receptor for AGE (RAGE)-deficient (Ϫ/Ϫ) mice. The rationale for this approach was based on the consideration that RAGE, a multiligand member of the Ig superfamily (13,14), is the best characterized signal transduction receptor for AGE. Binding of AGE to RAGE results in an activation of key signal transduction pathways, such as NF-B and subsequent transcription of mediators for which a role was also claimed in the pathogenesis of uremic complications (15,16). To avoid this confounder, we performed the following study in nonuremic animals.Human peritoneal mesothelial cells also express RAGE (17). Furthermore, monoclonal anti-RAGE antibodies prevent fibrosis of the peritoneal membrane induced by hyperglycemia in a diabetic animal model (18). However, it is not certain whether anti-RAGE antibodies recognize structures other than the ligand binding domain of RAGE. The purpose of our experimental study was to address the following issues: (1) Whether AGE-RAGE interruption, demonstrated in a RAGE Ϫ/Ϫ mouse model, prevents peritoneal damage after long-term PD; (2) whether interruption of AGE-RAGE interaction also pre- Received February 10, 2005. Accepted October 18, 2005 Published online ahead of print. Publication date available at www.jasn.org.V.S. and C.M. contributed equally to this work.

Atopic dermatitis (AD) is a common inflammatory skin disorder and characterized by abnormalities in both skin barrier structures and alternations of the immune response. Molecular genetics have dramatically changed our vision of the micro-organisms colonizing the human skin and recently well-documented changes in the skin microbiome in atopic dermatitis have become evident. The microbiome shifts have been primarily documented during disease flares and localized to sites of disease predilection, e.g. folds or facial area. In contrast, active treatment has been associated with a recolonisation and higher cutaneous microbial diversity. Additionally to the known dysfunctions in barrier function of the skin (e.g. filaggrin mutations) and immunologic disturbances (e.g. Th2-shift), evidence is rising that atopic dermatitis is also connected to a dysbiosis of the microbial community without an invading pathogen. In the future the investigation of the patient’s skin microbiome may have a foothold in the clinician’s diagnostic repertoire and treatment of atopic dermatitis.

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The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.

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Cutavirus (CuV) is associated with cutaneous T-cell lymphoma (CTCL), of which parapsoriasis is a precursor. Our study reveals a significantly higher CuV-DNA prevalence in skin-swabs of parapsoriasis patients (6/13, 46.2%), compared to those of healthy adults (1/51, 1.96%). Eight patients (8/12, 66.7%) had CuV-DNA in biopsied skin, and four developed CTCL.

Staphylococcal enterotoxins have been shown to promote lymphoma-associated immune dysregulation. This study examined changes in the skin microbiome of parapsoriasis compared with intact skin. Swab microbiome specimens were taken of the parapsoriasis lesions of 13 patients. Control samples were taken from contralateral healthy sides of the body. Microbiotas were characterized by sequencing the V1-V3 region of the 16S ribosomal RNA bacterial genes on the Illumina MiSeq platform. The most common genera in the microbiome data were Propionibacterium (27.13%), Corynebacterium (21.20%) and Staphylococcus (4.63%). Out of the Staphylococcus sequences, 39.6% represented S. epidermidis, with the rest including S. hominis, S. capitis and unidentified species. No significant differences were observed between the patients' parapsoriasis and contralateral healthy skin or between large- and small-plaque parapsoriasis. Notable interpersonal variation was demonstrated. These results suggest that parapsoriasis is not associated with significant alterations in the cutaneous bacterial microbiome.

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