Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis

Background. Encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis are important complications of long-term peritoneal dialysis (PD). Podoplanin is expressed by mesothelial cells and lymphatic vessels, which are involved in inflammatory reactions in the peritoneal cavity. Methods. We studied 69 peritoneal biopsies from patients on PD (n = 16), patients with EPS (n = 18) and control biopsies taken at the time of hernia repair (n = 15) or appendectomy (n = 20). Immunohistochemistry was performed to localize podoplanin. Additionally, markers of endothelial cells, mesothelial cells, myofibroblasts (smooth muscle actin), proliferating cells, and double labelling for smooth muscle actin/podoplanin were used on selected biopsies. Results. Podoplanin was present on the endothelium of lymphatic vessels in the submesothelial fibrous tissue and on mesothelial cells. In patients on PD and in biopsies with appendicitis, the mesothelial cells demonstrated a cuboidal appearance and circumferential podoplanin staining, with gaps between the cells. The number of lymphatic vessels was variable, but prominent at sites of fibrosis. In patients with EPS, a diffuse infiltration of podoplanin-positive cells with a fibroblastic appearance was present in 15 out of 18 biopsies. This pattern was focally present in 3 out of 16 on PD and none in the 35 controls. The podoplanin-positive cells did not express the endothelial marker or the mesothelial marker (calretinin). Conclusions. EPS is characterized by a population of podoplanin and smooth muscle actin double-positive cells. Podoplanin might be a suitable morphological marker supporting the diagnosis and might be involved in the pathogenesis of EP

Incidence of and risk factors for hungry bone syndrome in 84 patients with secondary hyperparathyroidism

Joerg Latus,1 Meike Roesel,1 Peter Fritz,2 Niko Braun,1 Christoph Ulmer,3 Wolfgang Steurer,3 Dagmar Biegger,4 M Dominik Alscher,1 Martin Kimmel1 1Department of Internal Medicine, Division of Nephrology, Robert Bosch Hospital, Stuttgart, Germany; 2Department of Diagnostic Medicine, Robert Bosch Hospital, Stuttgart, Germany; 3Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany; 4Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tuebingen, Stuttgart, Germany Introduction: Secondary hyperparathyroidism develops in nearly all patients with end-stage renal disease. Parathyroidectomy is often performed when medical therapy fails. The most common postoperative complication, hungry bone syndrome (HBS), requires early recognition and treatment. Materials and methods: A total of 84 patients who underwent parathyroidectomy because of secondary hyperparathyroidism were investigated. Detailed analysis of laboratory parameters (calcium, phosphate, parathyroid hormone, hemoglobin, and urea levels) and baseline characteristics (age at time of surgery, duration of renal replacement therapy, and medication) was performed to detect preoperative predictors for the development of HBS. Results: Average overall follow-up of the cohort was 4.7 years. Within this time frame, 13 of 84 patients had to undergo a second surgery because of recurrent disease, and HBS occurred in 51.2%. Only decreased preoperative calcium levels and younger age at time of surgery were significant predictors of HBS. Minimal levels of calcium were detected 3 weeks after surgery. Preoperative vitamin D therapy could not prevent HBS and could not shorten the duration of intravenous calcium supplementation. Conclusion: HBS is a very common complication after parathyroidectomy. Younger patients and patients with low preoperative calcium levels were at higher risk for the development of HBS. Remarkably, preoperative vitamin D therapy could not prevent HBS and had no impact on the length of intravenous calcium supplementation. Intensive monitoring of calcium levels must be performed for at least 3 weeks after surgery. Keywords: secondary hyperparathyroidism, parathyroidectomy, hungry bone syndrom

Platelet-derived growth factor receptor-β expression in human peritoneum

INTRODUCTION: Simple peritoneal fibrosis and encapsulating peritoneal sclerosis (EPS) are important lesions in the peritoneum of patients on peritoneal dialysis (PD). We have previously described a population of podoplanin-positive myofibroblasts in peritoneal biopsies from patients with EPS. Platelet-derived growth factor receptor-β (PDGFRβ) is a marker of pericytes, and PDGFs might be involved in the fibrotic response of the peritoneum. This study aimed to describe PDGFRβ in the human peritoneum. METHODS: In this retrospective analysis, we localized PDGFRβ in peritoneal biopsies from patients with EPS (n = 6) and patients on PD without signs of EPS (n = 5), and compared them with normal peritoneum (n = 4) and peritoneum from uremic patients (n = 5). Consecutive sections were stained for smooth-muscle actin (SMA) and podoplanin. Slides were scored semiquantitatively by 2 observers blinded to the diagnosis. RESULTS: PDGFRβ was expressed by cells of arterial walls in all biopsies. A prominent population of PDGFRβ-positive cells was present in the normal peritoneum, which were SMA negative on consecutive sections. In patients on PD, a high number of PDGFRβ were also positive for SMA. In EPS, the majority of podoplanin-positive cells were positive for PDGFRβ. In peritoneal biopsies from normal and uremic patients, the expression of SMA was mainly restricted to cells of arterial walls. Podoplanin expression was restricted to lymphatic vessels in normal peritoneum, in uremic patients, and in patients on PD without EPS. CONCLUSIONS: As podoplanin-positive myofibroblasts express PDGFRβ, these cells might be related to pericytes (rather than other sources of fibroblasts). PDGFRβ might turn out to be a therapeutic target in EPS. © 2014 S. Karger AG, Basel

CD147 expression in peritoneal injury

BACKGROUND: Peritoneal injury is an important cause of technical failure of long-term peritoneal dialysis (PD). Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term PD with potentially life threatening consequences. CD147 is a glycoprotein with diverse functions including modulation of extracellular matrix via induction of matrix metalloproteinases, cell adhesion, and regulation of immune reactions. We hypothesized that CD 147 plays a role in the peritoneal cavity. METHODS: In this retrospective study, we localized CD147 by immunohistochemistry in peritoneal biopsies from uremic patients not on PD (n = 8), on PD without signs of EPS (n = 7), and in biopsies in patients with the diagnosis of EPS (n = 7). Double immunofluorescence was used to co-localize α-smooth-muscle actin (α-SMA) and CD147 in selected biopsies from each group. Expression was scored semi-quantitatively. RESULTS: In biopsies from uremic controls, CD147 was prominently expressed in mesothelial cells, focally between fat cells and by some perivascular cells. In patients on PD, a similar distribution was present (although mesothelium was rarely conserved), with some focal accentuation. In EPS, layers of fibroblastic cells were positive for CD147. EPS biopsies demonstrated a significantly higher score in a blinded evaluation, compared to uremic patients. Cells expressing CD147 were α-SMA positive myofibroblasts as demonstrated by double immunofluorescence. Mean CD147 scores did not differ between patients with different transporter status. CONCLUSIONS: This is the first study demonstrating CD147 on a major part of fibroblastic cells in EPS. Future studies need to address the role of these cells in this severe complication of long-term PD

Histological criteria for encapsulating peritoneal sclerosis - a standardized approach

BACKGROUND: The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPS METHODS: We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients. RESULTS: THE FOLLOWING FINDINGS WERE SIGNIFICANTLY MORE COMMON IN EPS THAN IN PATIENTS ON PD WITHOUT EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%. CONCLUSION: The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database

N -heteroacenes as a new class of non-fullerene electron acceptors for organic bulk-heterojunction photovoltaic devices

Herein, we present the first investigation of N-heteroacenes as acceptors in bulk-heterojunction solar cells. The optical and electronic properties of tetraazapentacene (TIPS-TAP), triptycenyl-tetraazapentacene (TIPS-TAP-1T), and bistriptycenyl-tetraazapentacene (TIPS-TAP-2T) compounds are characterized by UV-vis, photothermal deflection, and ultraviolet photoemission spectroscopies. We compare the photovoltaic performance of the N-heteroacenes and find that cells with TIPS-TAP-2T significantly outperform the other derivatives, achieving a power conversion efficiency of 2.5% without extensive optimization or processing additives. We characterize the morphology and order within the active layer by atomic force microscopy and grazing incidence wide-angle scattering measurements, and find that blends with TIPS-TAP result in a gross phase separation driven by its strong crystallization. The substitution with triptycenyl units suppresses this crystallization resulting in amorphous films with a finer intermixing and a smooth surface structure. Finally, we investigate the photophysics of charge separation at the donor/acceptor interface and find that it is fundamentally different from the “conventional” polymer-fullerene systems. In blends with the tetraazapentacene derivatives, exciton dissociation is relatively slow and charge separation is strongly field dependent. We observe improved charge generation and significantly reduced recombination for TIPS-TAP-2T as compared to the other derivatives, which in combination with the improved film microstructure is responsible for the enhanced photovoltaic performance

Struktury proudění při vírovém toku – podmínka rozpadu víru

Příspěvek se zaměřuje na experimentální a numerickou analýzu vírového toku v trubici. Vírový tok je možné sledovat v technických aplikacích i v přírodě zejména tam, kde je zapotřebí efektivní přenos tepla a dobré promíchávání tekutiny. Proudová pole a struktury vírů a jejich redistribuce zde hrají klíčovou roli. Vírový tok je v tomto případě studován experimentálně využitím metody PIV a numericky využitím komerčního CFD balíku ANSYS CFX. Studovány jsou tři případy režimů proudění: laminární režim (Re = 1000), přechodový režim (Re = 2000) a turbulentní režim (Re = 5000). Redistribuce rychlosti a pokles vírovosti směrem k výstupu z trubice jsou charakteristickými v tomto typu proudění. Tyto jevy značné ovlivňují Reynoldsovo číslo. Z tohoto plyne, že využitím Rossbyho čísla, byl také studován rozpad víru. Je ukázáno, že rozpad víru je prokazatelnější u toků s vyšším Reynoldsovo číslem, kde lze také pozorovat osový zpětný tok. Charakter Reynoldsových čísel Re_phi a Re_z rovněž potvrzují toto tvrzení. Dále je v příspěvky představena analýza rozpadu víru z hlediska termodynamické podmínky stability.This paper presents an experimental and numerical analysis of swirl flow in a circular tube. Swirl flow is important for technical and natural processes, where high heat transfer and good fluid mixing are needed. Flow and vortex structures respecting redistribution of momentum and possible occurrence of vortex breakdown are taken into account. The swirl flow is analysed experimentally by the measurement of the velocity field using Particle Image Velocimetry (PIV) and numerically via the commercial CFD code ANSYS CFX. Three cases are investigated: laminar flow regime (Re = 1,000), intermediate flow regime (Re = 2,000), and turbulent flow regime (Re = 5,000). The redistribution of the velocity field and the decrease of the swirl strength towards the outlet are shown. This redistribution affects the Reynolds number. Concerning the Rossby number, the occurrence of vortex breakdown in the swirl flow is determined. It is shown that the vortex breakdown takes place in the flow with higher Reynolds numbers, where an axial backflow may occur. Changes of the Reynolds numbers Re_phi and Re_z along the tube length also confirm this statement. Furthermore, a thermodynamic perspective of vortex breakdown phenomena is presented

Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis are important complications of long-term peritoneal dialysis (PD). Podoplanin is expressed by mesothelial cells and lymphatic vessels, which are involved in inflammatory reactions in the peritoneal cavity. METHODS: We studied 69 peritoneal biopsies from patients on PD (n = 16), patients with EPS (n = 18) and control biopsies taken at the time of hernia repair (n = 15) or appendectomy (n = 20). Immunohistochemistry was performed to localize podoplanin. Additionally, markers of endothelial cells, mesothelial cells, myofibroblasts (smooth muscle actin), proliferating cells, and double labelling for smooth muscle actin/podoplanin were used on selected biopsies. RESULTS: Podoplanin was present on the endothelium of lymphatic vessels in the submesothelial fibrous tissue and on mesothelial cells. In patients on PD and in biopsies with appendicitis, the mesothelial cells demonstrated a cuboidal appearance and circumferential podoplanin staining, with gaps between the cells. The number of lymphatic vessels was variable, but prominent at sites of fibrosis. In patients with EPS, a diffuse infiltration of podoplanin-positive cells with a fibroblastic appearance was present in 15 out of 18 biopsies. This pattern was focally present in 3 out of 16 on PD and none in the 35 controls. The podoplanin-positive cells did not express the endothelial marker or the mesothelial marker (calretinin). CONCLUSIONS: EPS is characterized by a population of podoplanin and smooth muscle actin double-positive cells. Podoplanin might be a suitable morphological marker supporting the diagnosis and might be involved in the pathogenesis of EPS

Association between podoplanin pattern and clinical parameters and morphological scores of inflammatory cells.

<p>Illustrated are the mean C reactive protein (CRP) levels (A), the mean duration of symptoms (in months, B), the mean scores for CD3 positive T cells (C) and the mean scores for CD68 positive cells (D) for the four histological groups of podoplanin patterns. The infiltrating cells were scored semi-quantitatively as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053382#s4" target="_blank">materials and methods</a>.</p