High Macrophage Densities in Native Kidney Biopsies Correlate With Renal Dysfunction and Promote ESRD.

Introduction: Macrophages and monocytes are main players in innate immunity. The relevance of mononuclear phagocyte infiltrates on clinical outcomes remains to be determined in native kidney diseases. Methods: Our cross-sectional study included 324 patients with diagnostic renal biopsies comprising 17 disease entities and normal renal tissues for comparison. All samples were stained for CD68+ macrophages. Selected groups were further subtyped for CD14+ monocytes and CD163+ alternatively activated macrophages. Using precise pixel-based digital measurements, we quantified cell densities as positively stained areas in renal cortex and medulla as well as whole renal tissue. Laboratory and clinical data of all cases at the time of biopsy and additional follow-up data in 158 cases were accessible. Results: Biopsies with renal disease consistently revealed higher CD68+-macrophage densities and CD163+-macrophage densities in cortex and medulla compared to controls. High macrophage densities correlated with impaired renal function at biopsy and at follow-up in all diseases and in diseases analyzed separately. High cortical CD68+-macrophage densities preceded shorter renal survival, defined as requirement of permanent dialysis. CD14+ monocyte densities showed no difference compared to controls and did not correlate with renal function. Conclusion: Precise quantification of macrophage densities in renal biopsies may contribute to risk stratification to identify patients with high risk for end-stage renal disease (ESRD) and might be a promising therapeutic target in renal disease.

[Perforator based flaps of lateral thoracic artery (LTAP) and thoracodorsal artery (TDAP) for axillary reconstruction in patients with hidradenitis suppurativa]. / Die Verwendung lokaler Perforatorlappenplastiken der Arteria thoracica lateralis (LTAP) und Arteria thoracodorsalis (TDAP) zur axillären Rekonstruktion bei Hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic inflammatory disease of apocrine gland-bearing skin, especially in the axilla. The coverage of large defects in the region of the axilla after radical resection poses a challenge to reconstructive surgery. The lateral chest offers, among others, two options for perforator flaps: the thoracodorsal artery perforator flap and the lateral thoracic artery perforator flap. This article introduces the lateral thoracic artery flap as an additional option for defect restoration alongside the thoracodorsal artery perforator flap. A total of 13 flaps (10 lateral thoracic artery perforator flaps and 3 thoracodorsal artery perforator flaps) were used for defect reconstruction in 10 patients with axillary hidradenitis suppurativa stages II or III. All patients were assessed for surgical complications pursuant to the classification of Clavien-Dindo, subjective aesthetic results, recurrence rate, and maximum abduction angle evaluated by measuring the range of motion. All flaps healed without major or partial flap necrosis. In 12 out of 13 flaps, the aesthetic result was rated very good or good.Only one patient complained of a visible scar, but rated the overall result as satisfactory. The range of motion in the shoulder was unlimited in all cases with a maximum abduction angle of 178.8 ± 4.2°. Recurrence was not observed in any case during the postsurgical follow-up of 27.2 ± 14.4 months. The use of the two perforator-based fasciocutaneous flaps of the thoraco dorsal artery and the lateral thoracic artery offers a useful and reliable option for the reconstruction of large axillary defects while maintaining full shoulder movement and providing cosmetically satisfactory results.

Atmospheric sulfur and nitrogen deposition in the Athabasca oil sands region is correlated with foliar nutrient levels and soil chemical properties.

The oil extraction industry and human activity in north eastern Alberta has been growing steadily since the 1960's and is a source of air pollution. In the late 1990's the Wood Buffalo Environmental Association was established to monitor air quality for both public and environmental health. A primary environmental concern was soil acidification caused by sulfur (S) and nitrogen (N) deposition. A network of forest health monitoring (FHM) sites was established in dry jack pine ecosystems to serve as an early indicator of negative impacts. A sampling campaign was executed in 2011 and this study examines soil properties and foliar nutrients in the context of measured and modeled acid deposition. Total N (TN), SO42-, pH, base cation to aluminum ratio (BC:Al), and base saturation (% BS) are reported for the organic layer (LFH) and 3 depths in the mineral soil, while foliar nutrients were analysed from current annual growth in jack pine needles. Atmospheric deposition of S, N, BC, and potential acid input (PAI) in the study area was recently provided by Edgerton et al. (2020) and soil and foliar chemistry was evaluated based on deposition estimates and measurements. Inverse distance weighting was used to examine spatial patterns and regression analysis was used to quantify relationships between variables. The results indicated that S deposition is spatially correlated with foliar SO42- concentration, and LFH SO42-, but not mineral topsoil (0-5 cm) SO42-. Nitrogen deposition was spatially correlated with foliar N concentration, but not LFH or topsoil TN indicating potential uptake by the foliage or rapid uptake by roots in the LFH layer. High BC deposition in the same areas with the highest potential acid inputs (PAI) did not correlate significantly with changes in soil pH. However, LFH pH was significantly related to dry NH3 deposition, which has not been reported previously and requires further investigation.

The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10.

The novel CXC-chemokine ligand 16 (CXCL16) functions as transmembrane adhesion molecule on the surface of APCs and as a soluble chemoattractant for activated T cells. In this study, we elucidate the mechanism responsible for the conversion of the transmembrane molecule into a soluble chemokine and provide evidence for the expression and shedding of CXCL16 by fibroblasts and vascular cells. By transfection of human and murine CXCL16 in different cell lines, we show that soluble CXCL16 is constitutively generated by proteolytic cleavage of transmembrane CXCL16 resulting in reduced surface expression of the transmembrane molecule. Inhibition experiments with selective hydroxamate inhibitors against the disintegrin-like metalloproteinases a disintegrin and metalloproteinase domain (ADAM)10 and ADAM17 suggest that ADAM10, but not ADAM17, is involved in constitutive CXCL16 cleavage. In addition, the constitutive cleavage of transfected human CXCL16 was markedly reduced in embryonic fibroblasts generated from ADAM10-deficient mice. By induction of murine CXCL16 in ADAM10-deficient fibroblasts with IFN-gamma and TNF-alpha, we show that endogenous ADAM10 is indeed involved in the release of endogenous CXCL16. Finally, the shedding of endogenous CXCL16 could be reconstituted by retransfection of ADAM10-deficient cells with ADAM10. Analyzing the expression and release of CXCXL16 by cultured vascular cells, we found that IFN-gamma and TNF-alpha synergize to induce CXCL16 mRNA. The constitutive shedding of CXCL16 from the endothelial cell surface is blocked by inhibitors of ADAM10 and is independent of additional inhibition of ADAM17. Hence, during inflammation in the vasculature, ADAM10 may act as a CXCL16 sheddase and thereby finely control the expression and function of CXCL16 in the inflamed tissue.

Matrix metalloproteinase-19 expression in normal and diseased skin: dysregulation by epidermal proliferation.

Most of the matrix metalloproteinases (MMP) are not expressed in normal intact skin but they are upregulated in inflamed or diseased skin. The recently cloned MMP-19 is one of the few MMP members that are also expressed in healthy epidermis. In this study, we found that MMP-19 is generally coexpressed with cytokeratin 14 that is confined to keratinocytes of the stratum basale. MMP-19 was also detected in hair follicles, sebaceous glands, and eccrine sweat glands. Its expression, however, changed in cutaneous diseases exhibiting increased alternations of epidermal proliferation, such as psoriasis, eczema, and tinea. In the affected area, MMP-19 was also found in suprabasal and spinous epidermal layers. We also studied the regulation of MMP-19 expression at the protein level, as well as by using a promoter assay. The constitutive expression of MMP-19 was upregulated with phorbol myristate acetate and downregulated with retinoic acid and dexamethasone. Tumor necrosis factor-alpha, interleukin (IL)-6, TGF-beta, IL-15, IL-8, and RANTES as well as the bacterial compounds lipopolysaccharide and lipoteichoic acid did not show any profound effect in HaCaT cells. In contrast, type IV and type I collagens upregulated MMP-19 significantly. The dysregulation of MMP-19 expression in epidermis suggests its possible involvement in the perpetuation of cutaneous infections and proliferative disorders such as psoriasis.