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Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups omeprazole (n = 32), pantoprazole (n = 25), esomeprazole (n = 3) and no PPI (n = 18). Patients with no PPI had no significant difference in plasma voriconazole concentration when compared with those with PPI (2.63 ± 2.13 μg/mL [95% confidence interval CI 1.57-3.69] vs 2.11 ± 1.73 μg/mL [95%CI 1.67-2.55], P > .05). However, voriconazole plasma concentration was significantly lower in patients treated with pantoprazole vs those treated with omeprazole (1.44 ± 1.22 μg/mL [95%CI 0.94-1.94) vs 2.67 ± 1.88 μg/mL [95%CI 2.02-3.32], P = .013) suggesting a greater CYP2C19 enzyme inhibitory effect of omeprazole. This study demonstrates the greater CYP inhibition capacity of omeprazole and should be helpful for the choice of PPIs for patients treated with voriconazole. © 2020 The British Pharmacological Society.Rh immune globulin (RhIG) may be administered to Rh(D)-negative recipients of Rh(D)-positive platelet (PLT) transfusions to mitigate anti-D alloantibody formation. We report a series of seven patients in which anti-C was detected as a result of RhIG administered as immunoprophylaxis following Rh-mismatched apheresis PLT transfusion, persisting for a range of 27 to 167 days post-RhIG. The passively transferred anti-C antibodies created complexities for subsequent transfusion support. Based on these challenges, in combination with emerging evidence supporting an extremely low anti-D alloimmunization risk following Rh-mismatched apheresis PLTs, we have changed our practice and now limit RhIG immunoprophylaxis in this setting to women of reproductive age. In summary, the blood bank and apheresis communities should be aware that passive transfer of non-D antibodies is possible following RhIG administration. This phenomenon represents a compelling reason to consider the risk/benefit ratio of RhIG and to limit its use to situations in which it is clinically necessary. © 2020 Wiley Periodicals, Inc.Buparlisib is a selective phosphoinositide 3 kinase inhibitor currently evaluated in clinical trials. We developed and validated an LC-MS/MS coupled with a one-step protein precipitation extraction method for the quantitation of buparlisib in rat plasma. After protein precipitation with acetonitrile, the plasma sample was analyzed using a Cortecs UPLC C18 column, with acetonitrile-0.1% formic acid as the mobile phase system. Mass spectrometric detection was conducted in positive ionization mode, with target quantitative ion pair of m/z 411.2 → 367.2 for buparlisib. The calibration curve showed good linearity (1.0-3000 ng/ml), with acceptable accuracy (RE ranging from -6.2 to 5.9%) and precision (RSD within 8.2%) values at quality control concentrations. Extraction recovery from plasma was 80.9-88.7% and the matrix effect was negligible (92.6-95.2%). The validated method presented a simple quantification method of buparlisib in detail and utilized it for a pharmacokinetic study at three dose concentrations after oral administration in Wistar rats. © 2020 John Wiley & Sons, Ltd.Cataract is the major reason for human blindness worldwide. α-Crystallin, as a key chaperone of eye lenses, keeps the lenticular tissues in its transparent state over time. In this study, cataract-causing familial mutations, P20R and A171T, were introduced in CRYАB gene. After successful expression in Escherichia coli and subsequent purification, the recombinant proteins were subjected to extensive structural and functional analyses using various spectroscopic techniques, gel electrophoresis, and electron microscopy. The results of fluorescence and Raman assessments suggest important but discreet conformational changes in human αB-Cry upon these cataractogenic mutations. Furthermore, the mutant proteins exhibited significant secondary structural alteration as revealed by FTIR and Raman spectroscopy. An increase in conformational stability was seen in the human αB-Cry bearing these congenital cataractogenic mutations. The oligomeric size distribution and chaperone-like activity of human αB-Cry were significantly altered by these mutations. The P20R mutant protein was observed to loose most of the chaperone-like activity. Finally, these cataractogenic mutant proteins exhibited an increased propensity to form the amyloid fibrils when incubated under environmental stress. https://www.selleckchem.com/products/bexotegrast.html Overall, the structural and functional changes in mutated human αB-Cry proteins can shed light on the pathogenic development of congenital cataracts. © 2020 Wiley Periodicals, Inc.Patch testing is a common procedure, where the baseline series is frequently used as a first screening. The number and the specific allergens of these series varies from country to country and keep changing over the years. Although the European Society of Contact Dermatitis (ESCD) made recommendations about patch testing1 , the decisions about the European baseline series were traditionally delegated to the European Environmental Contact Dermatitis Research Group (EECDRG)2 . A different, more reactive, approach has been recently proposed by the ESCD task force3 , using data provided by the European Surveillance System on Contact Allergies (ESSCA) to generate initial discussion. The main criteria for the addition of a new allergen is that the prevalence of allergy is 0.5-1% or higher4 , and positive results should be relevant. This article is protected by copyright. All rights reserved.BACKGROUND This is the first national survey of residents and fellows in pediatric cardiology in Germany evaluating training, research activity, and the general working environment. METHODS An online questionnaire including 62 questions (SurveyMonkey) was developed by the "Junges Forum" of the German Society of Pediatric Cardiology. Fellows and residents during training and up to 3 years after completing their pediatric cardiology fellowship were invited to participate. RESULTS A total of 102 pediatric cardiology fellows and residents completed the questionnaire. Many participants complained about their training as being unstructured (47%) and non-transparent (37%). The numbers of technical and catheter interventions required by the national medical board in Germany cannot be achieved, especially regarding invasive procedures. Sixty per cent work more than contractually agreed, usually in Germany it is 40 hours daytime work plus on calls, while 90% of all participants prefer less than 50 weekly working hours; 50% of the participants are engaged in research that is usually done during their spare time.
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