Steady-state and pulsed current multi-ion simulations for a thallium electrodeposition process

A numerical simulation and optimization tool for pulsed current electroplating processes is applied to the industrial preparation of high quality Tl-203 deposits. Reliable predictions on current efficiency and deposit quality are enabled by the construction of an adequate reaction mechanism for Tl deposition from highly basic solutions (pH >12.5) in the presence of the EDTA complexing agent. In order to account for multi-ion mass transfer effects near the electrode, the diluted electrochemical ionic system model is to be solved without simplifications, in combination with electron transfer and homogeneous complex forming reactions as defined by the proposed reaction mechanism. Physical and chemical parameters for this model are achieved by comparing and tuning simulated steady-state polarization and efficiency curves at a rotating disc electrode (RDE) with experimental data.     

Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1

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The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis

R126638 is a novel triazole with in vitro activity similar to that of itraconazole against dermatophytes, Candida spp., and Malassezia spp. In animal models of dermatophyte infections, R126638 showed superior antifungal activity. R126638 inhibits ergosterol synthesis in Candida albicans, Trichophyton mentagrophytes, Trichophyton rubrum, and Microsporum canis at nanomolar concentrations, with 50% inhibitory concentrations (IC(50)s) similar to those of itraconazole. The decreased synthesis of ergosterol and the concomitant accumulation of 14 alpha-methylsterols provide indirect evidence that R126638 inhibits the activity of CYP51 that catalyzes the oxidative removal of the 14 alpha-methyl group of lanosterol or eburicol. The IC(50)s for cholesterol synthesis from acetate in human hepatoma cells were 1.4 microM for itraconazole and 3.1 microM for R126638. Compared to itraconazole (IC(50) = 3.5 microM), R126638 is a poor inhibitor of the 1 alpha-hydroxylation of 25-hydroxyvitamin D(3) (IC(50) > 10 microM). Micromolar concentrations of R126638 and itraconazole inhibited the 24-hydroxylation of 25-hydroxyvitamin D(3) and the conversion of 1,25-dihydroxyvitamin D(3) into polar metabolites. At concentrations up to 10 microM, R126638 had almost no effect on cholesterol side chain cleavage (CYP11A1), 11 beta-hydroxylase (CYP11B1), 17-hydroxylase and 17,20-lyase (CYP17), aromatase (CYP19), or 4-hydroxylation of all-trans retinoic acid (CYP26). At 10 microM, R126638 did not show clear inhibition of CYP1A2, CYP2A6, CYP2D6, CYP2C8, CYP2C9, CYP2C10, CYP2C19, or CYP2E1. Compared to itraconazole, R126638 had a lower interaction potential with testosterone 6 beta hydroxylation and cyclosporine hydroxylation, both of which are catalyzed by CYP3A4, whereas both antifungals inhibited the CYP3A4-catalyzed hydroxylation of midazolam similarly. The results suggest that R126638 has promising properties and merits further in vivo investigations for the treatment of dermatophyte and yeast infections.     

Range of motion in femoroacetabular impingement

Recent epidemiological studies have demonstrated that radiographic features specific to femoroacetabular impingement appear far more frequently in healthy and asymptomatic cohorts than previously anticipated. It remains unclear how incidental findings should be interpreted clinically. In addition, several authors have suggested that a decreased range of motion is part of the clinical presentation of femoroacetabular impingement. The purpose of the present study was to describe and analyze differences in range of motion between femoroacetabular impingement patients, asymptomatic individuals with incidental radiographic findings and healthy controls, using a validated electromagnetic tracking system. Furthermore, it was evaluated which motions were clinically relevant and could be used to differentiate between these three groups. We found all evaluated motions to differ significantly between patients and controls. The anterior impingement test showed a significant difference between patients and asymptomatic cases. In conclusion, functional evaluation of the range of motion appeared in this study as a useful tool in the diagnostic work-up of femoracetabular impingement.     

Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains

We investigated the effects of combining tacrolimus and azole antifungal agents in azole-resistant strains of Candida albicans by comparing the accumulation of [3H]itraconazole. The CDR1-expressing resistant strain C26 accumulated less itraconazole than the CaMDR-expressing resistant strain C40 or the azole-sensitive strain B2630. A CDR1-expressing Saccharomyces cerevisiae mutant, DSY415, showed a marked reduction in the accumulation of both fluconazole and itraconazole. A CaMDR-expressing S. cerevisiae mutant, DSY416, also showed lower accumulation of fluconazole, but not of itraconazole. The addition of sodium azide, an electron-transport chain inhibitor, increased the intracellular accumulation of itraconazole only in the C26 strain, and not in the C40 or B2630 strains. Addition of tacrolimus, an inhibitor of multidrug resistance proteins, resulted in the highest increase in itraconazole accumulation in the C26 strain. The combination of itraconazole and tacrolimus was synergic in azole-resistant C. albicans strains. In the C26 strain, the MIC of itraconazole decreased from >8 to 0.5 mg/L when combined with tacrolimus. Our results showed that two multidrug resistance phenotypes (encoded by the CDR1 and CaMDR genes) in C. albicans have different substrate specificity for azole antifungal agents and that a combination of tacrolimus and azole antifungal agents is effective against azole-resistant strains of C. albicans.     

Comparison of the reticulocyte mode of the Abx Pentra 120 Retic,Coulter® General‐S™, Sysmex® SE 9500, Abbott CD 4000 and Bayer Advia® 120 haematology analysers in a simultaneous evaluation

The Abx Pentra 120 Retic, Coulter^® General‐S?, Sysmex^® SE 9500, Abbott Cell Dyn^® 4000 and Bayer Advia^® 120 were evaluated simultaneously in a general hospital laboratory. Linearity, precision, sample stability, carry‐over and comparability of the reticulocyte mode were determined following International Council for Standardization in Haematology guidelines for the evaluation of blood cell analysers. All analysers showed good results for dilution, stability and carry‐over testing. The between‐batch coefficient of variation of the General‐S? was high compared to the other analysers evaluated. Multiple correlation studies showed good agreement for all analysers in the normal and high reticulocyte range, with correlation coefficients above 0.7. Multiple correlation studies for reticulocytopenic samples (< 15.10⁹/l) were less satisfactory, with a wider range of correlation coefficients (r‐values 0.0–0.9). Overall, the General‐S?, SE 9500 and Advia^® 120 gave lower reticulocyte counts than the Pentra 120 Retic and CD 4000. Reagent costs were also evaluated. Reagent consumption was close to the manufacturers’ specifications for the SE 9500 (Search reagent), CD 4000 (CD Retic) and Advia^® 120 (Retics) but was higher than stated for the Pentra 120 Retic (Retix), General‐S? (Retic kit) and SE 9500 (Sheath reagent). Our results show that these new generation haematology analysers will meet the needs of hospital laboratories for reliable and cost‐effective reticulocyte counting.