Effect of high glucose concentration on the synthesis of monocyte chemoattractant protein-1 in human peritoneal mesothelial cells: Involvement of protein kinase C

Human peritoneal mesothelial cells (HMC) contribute to the activation and control of inflammatory processes in the peritoneum by their potential to produce various inflammatory mediators. The present study was designed to assess the effect of glucose, the osmotic active compound in most commercially available peritoneal dialysis fluids, on the synthesis of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured HMC. The MCP-1 concentration in the cell supernatants was determined by enzyme-linked immunosorbent assay and the MCP-1 mRNA expression was examined using Northern blot analysis. Incubation of HMC with glucose (30-120 mM) resulted in a time- and concentration-dependent increase in MCP-1 protein secretion and mRNA expression. After 24 h the MCP-1 synthesis was increased from 2.8 +/- 0.46 to 4.2 +/- 0.32 ng/10(5) cells (n = 5, p 2001 S. Karger AG. Basel

Non-invasive monitoring of renal transplant recipients: Urinary excretion of soluble adhesion molecules and of the complement-split product C4d

Background: The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. Methods: Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: group 1: acute steroid-sensitive rejection (ASSR, n=14), group 2: acute steroid-resistant rejection (ASRR, n=12), group 3: chronic allograft dysfunction (CAD, n=20) and group 4: stable graft function (SGF, n=29). Results: All patients with rejection episodes (groups 1-3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p<0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p<0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p<0.05). Conclusion: The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment. Copyright (C) 2003 S. Karger AG, Basel

Strahlenschäden in Szintillator-Materialien für die Hochstrom-Diagnose von Schwerionenstrahlen

Diese Arbeit behandelt die Untersuchung des Szintillationsverhaltens keramischer Leuchtschirme für die Abbildung von Ionenstrahlen. Leuchtschirme werden an Beschleunigeranlagen in der Strahldiagnose verwendet, um ein zweidimensionales Strahlprofil des Ionenstrahls zu erhalten und somit Lage, Form und die Intensitätsverteilung des Strahls zu bestimmen. Es wurden verschiedene keramische Materialien wie Aluminiumoxid (Al2O3), Mischoxide (partikelverstärktes Al2O3/ZrO2, teilstabilisiertes ZrO2/MgO), sowie Nitride (AlN, h-BN) hinsichtlich ihrer Szintillationseigenschaften unter Schwerionenbestrahlung untersucht. Die Experimente wurden an zwei Beschleunigeranlagen, dem UNILAC des GSI Helmholtzzentrums für Schwerionenforschung und dem 6 MV Tandetron-Beschleuniger des Helmholtz-Zentrums Dresden-Rossendorf, durchgeführt. Die Szintillatoren wurden unter Variation verschiedener Strahlparameter, wie der Projektilmasse (14N bis 209Bi), der Strahlenergie (0,5 bis 5,9 MeV/u), sowie der akkumulierten Teilchenfluenz, des Teilchenflux und der Targettemperatur (295 bis 973 K) bestrahlt. Die Lichtausbeute und die Emissionsspektren der Materialien wurden im Wellenlängenbereich von 320 bis 800 nm aufgezeichnet. Es kann eine Degradation der Lichtausbeute in Abhängigkeit der akkumulierten Fluenz beobachtet werden. Diese wird anhand des von Birks und Black entwickelten Strahlenschadenmodells evaluiert, um die Strahlenhärte der Materialien zu bestimmen. Es zeigt sich, dass reines Al2O3 das strahlenhärteste der untersuchten Materialien ist. Optische Absorptionsmessungen im Bereich von 200 bis 1000 nm belegen eine eindeutige Korrelation zwischen der Abnahme der Szintillation und der durch die Bestrahlung erzeugten Farbzentren im Material. Die Auswertung der Emissionsspektren offenbart ein komplexes Szintillationsverhalten in Abhängigkeit der akkumulierten Fluenz und der Targettemperatur. Es zeigt sich, dass die Degradation der Lichtausbeute bei Betreiben der Leuchtschirme unter erhöhten Temperaturen (573 bis 773 K) deutlich verlangsamt bzw. gestoppt werden kann. Die durch ein thermisches Quenching bedingte globale Abnahme der Lichtausbeute muss berücksichtigt werden. Dennoch kann mit dem Tempern der Materialien ein wirksames Instrument präsentiert werden, um die Lebensdauer der Leuchtschirme deutlich zu erhöhen. Begründet werden kann dieses Verhalten durch das thermische Ausheilen der durch die Bestrahlung erzeugten Farbzentren. Das isochrone und isotherme Ausheilungsverhalten bestrahlter Proben wurde im Temperaturbereich von 295 bis 1073 K sowie für verschiedene Temperzeiten von 15 bis 480 min untersucht. Die berechneten Aktivierungsenergien für das thermische Ausheilen der Farbzentren liegen zwischen 0,15 und 0,8 eV. Nach einer Temperzeit von 1 h bei 1073 K erhält das Material Al2O3 die ursprünglichen optischen Eigenschaften zurück

Reduced CD40L expression on ex vivo activated CD4+T-lymphocytes from patients with excellent renal allograft function measured with a rapid whole blood flow cytometry procedure

Background: The CD40-CD40L (CD154) costimulatory pathway plays a critical role in the pathogenesis of kidney allograft rejection. In renal transplant biopsies, CD4+ CD40L+ graft-infiltrating cells were detected during chronic rejection in contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure, we were able to demonstrate CD40L upregulation in peripheral blood of patients with chronic renal allograft dysfunction. Materials and Methods: Whole blood from recipients of renal allografts was stimulated with PMA and ion-omycin and measured by flow cytometry. Patients were assigned to three groups based on transplant function. Group 1: 26 patients with excellent renal transplant function; group 2: 28 patients with impaired transplant function; group 3: 14 patients with chronic allograft dysfunction and group 4: 8 healthy controls. Results: The median percentage +/-SEM of CD4+/ CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0% and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different CD40L expression patterns. Patients with increased serum creatinine since the initial phase after transplantation ( groups 2a and 3a) revealed a higher percentage of CD4+ CD40L+ cells than patients showing a gradual increase over time ( groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly reduced transplant function compared with those of group 3b. Conclusion: After PMA + ionomycin stimulation, patients with excellent kidney graft function displayed significantly reduced expression of CD40L surface molecules on CD4+ cells early after transplantation. Those with a chronic dysfunction of the renal graft showed significantly more CD4+ cells expressing CD40L compared to the other transplanted groups. These results demonstrate that the percentage of CD4+ CD40L+ cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic allograft nephropathy. Copyright (C) 2004 S. Karger AG, Basel

Persistent nasal methicillin-resistant staphylococcus aureus carriage in hemodialysis outpatients: a predictor of worse outcome

Background: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a well defined risk factor for subsequent bacteremia and death in various groups of patients, but its impact on outcome in patients receiving long-term hemodialysis (HD) is under debate. Methods: This prospective interventional cohort study (performed 2004 to 2010) enrolled 289 HD outpatients of an urban dialysis-unit. Nasal swab cultures for MRSA were performed in all patients upon first admission, at transfer from another dialysis facility or readmission after hospitalisation. Nasal MRSA carriers were treated in a separate ward and received mupirocin nasal ointment. Concomitant extra-nasal MRSA colonization was treated with 0.2% chlorhexidine mouth rinse (throat) or octenidine dihydrochloride containing antiseptic soaps and 2% chlorhexidine body washes (skin). Clinical data and outcome of carriers and noncarriers were systematically analyzed. Results: The screening approach identified 34 nasal MRSA carriers (11.7%). Extra-nasal MRSA colonization was observed in 11/34 (32%) nasal MRSA carriers. History of malignancy and an increased Charlson Comorbidity Index were significant predictors for nasal MRSA carriers, whereas traditional risk factors for MRSA colonization or markers of inflammation or malnutrition were not able to discriminate. Kaplan-Meier analysis demonstrated significant survival differences between MRSA carriers and noncarriers. Mupirocin ointment persistently eliminated nasal MRSA colonization in 26/34 (73.5%) patients. Persistent nasal MRSA carriers with failure of this eradication approach had an extremely poor prognosis with an all-cause mortality rate >85%. Conclusions: Nasal MRSA carriage with failure of mupirocin decolonization was associated with increased mortality despite a lack of overt clinical signs of infection. Further studies are needed to demonstrate whether nasal MRSA colonization represents a novel predictor of worse outcome or just another surrogate marker of the burden of comorbid diseases leading to fatal outcome in HD patients

Development of Photocatalytically Active Anodized Layers by a Modified Phosphoric Acid Anodizing Process for Air Purification

One of the key urban air quality issues is pollution by nitrogen oxides (NOx). To reduce NOx, facade cladding could be provided with photocatalytic properties by incorporating titanium dioxide nanoparticles. For this purpose, a modified phosphoric acid anodizing process (MPAA) was developed for the facade alloy EN AW-5005, in which highly ordered anodized structures with a low degree of arborization and tortuosity were produced. Pore widths between 70 nm and 150 nm and layer thicknesses of about 2–3 m were obtained. The subsequent impregnation was carried out by dip coating from water-based systems. Depending on the dip-coating parameters and the suspension used, the pores can be filled up to 60% with the TiO2 nanoparticles. Photocatalytic tests according to ISO 22197-1 certify a high photocatalytic activity was obtained with rPCE values > 8 and with rPCE > 2, achieving “photocatalytically active for air purification”. Tests on the corrosion resistance of the anodized coatings with a commercially available aluminum and facade cleaner confirm a protective effect of the anodized coatings when compared with nonanodized aluminum material, as well as with compacted anodized layers

Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts

Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts.BackgroundThe contribution of humoral alloreactivity to the rejection of renal allografts is not well defined because humoral antigraft reactions are not easily detectable in transplant biopsies, and serial measurements of circulating allo-antibodies in the post-transplantation period are not routinely performed. We have developed diagnostic techniques that improve the assessment of humoral alloreactivity in vivo and in vitro.MethodsHumoral alloreactivity in transplant biopsies derived from 218 single kidney grafts was detected by assessing the deposition of complement fragment C4d in interstitial capillaries. Circulating alloantibodies were determined in corresponding serum samples by flow cytometry using lymphoblastoid cell lines of donor DR-type as target cells and by a conventional microcytotoxicity test. The impact of capillary C4d and other selected variables on renal graft survival was calculated by univariate and multivariate analysis.ResultsCapillary C4d, present in 46% of biopsies from first grafts and 72% of regrafts, is related to circulating alloantibodies. Grafts with capillary C4d have a markedly shorter survival than grafts without capillary C4d (50% graft survival, 4 vs. 8 years, P = 0.0001). Among several risk factors, capillary C4d is the strongest predictor of subsequent graft loss in a multivariate analysis (relative risk, 2.1, 95% CI, 1.4 to 3.1). Humoral alloreactivity detectable within six months after transplantation has a much stronger impact on graft survival than alloreactivity detected beyond this period.ConclusionsHumoral alloreactivity, manifested by the capillary deposition of complement C4d in about 50% of biopsied renal grafts, exerts a strong impact on graft survival when it operates within six months after transplantation

Non-invasive monitoring of renal transplant recipients: Urinary excretion of soluble adhesion molecules and of the complement-split product C4d

Background: The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. Methods: Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: group 1: acute steroid-sensitive rejection (ASSR, n=14), group 2: acute steroid-resistant rejection (ASRR, n=12), group 3: chronic allograft dysfunction (CAD, n=20) and group 4: stable graft function (SGF, n=29). Results: All patients with rejection episodes (groups 1-3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p<0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p<0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p<0.05). Conclusion: The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment. Copyright (C) 2003 S. Karger AG, Basel