156 research outputs found

    Spontaneous variability of pre-dialysis concentrations of uremic toxins over time in stable hemodialysis patients

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    Background and aim : Numerous outcome studies and interventional trials in hemodialysis (HD) patients are based on uremic toxin concentrations determined at one single or a limited number of time points. The reliability of these studies however entirely depends on how representative these cross-sectional concentrations are. We therefore investigated the variability of predialysis concentrations of uremic toxins over time. Methods : Prospectively collected predialysis serum samples of the midweek session of week 0, 1, 2, 3, 4, 8, 12, and 16 were analyzed for a panel of uremic toxins in stable chronic HD patients (N = 18) while maintaining dialyzer type and dialysis mode during the study period. Results : Concentrations of the analyzed uremic toxins varied substantially between individuals, but also within stable HD patients (intra-patient variability). For urea, creatinine, beta-2-micro-globulin, and some protein-bound uremic toxins, Intra-class Correlation Coefficient (ICC) was higher than 0.7. However, for phosphorus, uric acid, symmetric and asymmetric dimethylarginine, and the protein-bound toxins hippuric acid and indoxyl sulfate, ICC values were below 0.7, implying a concentration variability within the individual patient even exceeding 65% of the observed inter-patient variability. Conclusion : Intra-patient variability may affect the interpretation of the association between a single concentration of certain uremic toxins and outcomes. When performing future outcome and interventional studies with uremic toxins other than described here, one should quantify their intra-patient variability and take into account that for solutes with a large intra-patient variability associations could be missed

    Anti-Tumor Activity of Doxorubicin-loaded Boehmite Nanocontainers

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    Doxorubicin-filled boehmite nanocontainers, DOX@╬│-AlO(OH), with a mean diameter of 40 nm and a wall thickness of 10 nm are prepared via a microemulsion strategy and studied as drug carriers for cancer treatment. Nanocontainer structure and drug load are examined in detail based on different analytical tools. The DOX load is optimized on highest load at lowest side effects according to blood counts. Cell uptake, DOX-based fluorescence detection and systemic toxicity are evaluated based on in vitro and in vivo models. Toxicity and activity of the DOX@AlO(OH) nanocontainers are compared with non-filled AlO(OH) hollow spheres and free DOX as references and show promising results. An orthotopic breast cancer BALB/c mouse model validates the activity of DOX@AlO(OH) in vivo at lower side effects than for free DOX

    Binding of bromocresol green and bromocresol purple to albumin in hemodialysis patients

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    BACKGROUND: Colorimetric albumin assays based on binding to bromocresol purple (BCP) and bromocresol green (BCG) yield different results in chronic kidney disease. Altered dye binding of carbamylated albumin has been suggested as a cause. In the present study, a detailed analysis was carried out in which uremic toxins, acute phase proteins and Kt/V, a parameter describing hemodialysis efficiency, were compared with colorimetrically assayed (BCP and BCG) serum albumin. METHODS: Albumin was assayed using immunonephelometry on a BN II nephelometer and colorimetrically based on, respectively, BCP and BCG on a Modular P analyzer. Uremic toxins were assessed using high-performance liquid chromatography. Acute phase proteins (C-reactive protein and ╬▒1-acid glycoprotein) and plasma protein ╬▒2-macroglobulin were assayed nephelometrically. In parallel, Kt/V was calculated. RESULTS: Sixty-two serum specimens originating from hemodialysis patients were analyzed. Among the uremic toxins investigated, total para-cresyl sulfate (PCS) showed a significant positive correlation with the BCP/BCG ratio. The serum ╬▒1-acid glycoprotein concentration correlated negatively with the BCP/BCG ratio. The BCP/BCG ratio showed also a negative correlation with Kt/V. CONCLUSIONS: In renal insufficiency, the BCP/BCG ratio of serum albumin is affected by multiple factors: next to carbamylation, uremic toxins (total PCS) and ╬▒1-acid glycoprotein also play a role
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