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31.
A porous TiO2 layer was prepared with the plasma electrolytic oxidation (PEO) of Ti. In a further step, Pd was deposited on the TiO2 surface layer using the adsorption method. The activity of the Pd/TiO2/Ti catalyst was investigated during the oxidation of CO to CO2 in a mixture of air with 5% CO. The structure of the catalytic active layer was studied using a scanning electron microscope equipped with an energy dispersive spectrometer (SEM-EDS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), inductively coupled plasma mass spectrometry (ICP-MS), and X-ray diffraction (XRD). The PEO process provided a porous TiO2 layer with a uniform thickness in the range of 5–10 µm, which is desirable for the production of Pd-supported catalysts. A TOF-SIMS analysis showed the formation of Pd nanoparticles after the adsorption treatment. The conversion of CO to CO2 in all samples was achieved at 150–280 °C, depending on the concentration of Pd. The composition of Pd/ TiO2/Ti was determined using ICP-MS. The optimum concentration of Pd on the surface of the catalyst was approximately 0.14% wt. This concentration was obtained when a 0.4% PdCl2 solution was used in the adsorption process. Increasing the concentration of PdCl2 did not lead to a further improvement in the activity of Pd/ TiO2/Ti.  相似文献   
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The widely used alkylating agent cyclophosphamide (CY) has substantive interpatient variability in the area under the curve (AUC) of it and its metabolites. Numerous factors may influence the drug‐metabolizing enzymes that metabolize CY to 4‐hydroxycyclophosphamide (4HCY), the principal precursor to CY’s cytotoxic metabolite. We sought to identify endogenous metabolomics compounds (EMCs) associated with 4HCY formation clearance (ratio of 4HCY/CY AUC) using global metabolomics. Patients who undergo hematopoietic cell transplantation receiving post‐transplant CY (PT‐CY) were enrolled, cohort 1 (n = 26) and cohort 2 (n = 25) donating longitudinal blood samples before they started HCT (pre‐HCT), before infusion of the donor allograft (pre‐graft), before the first dose of PT‐CY (pre‐CY), and 24 h after the first dose of PT‐CY (24‐h post‐CY), which is also immediately before the second dose of CY. A total of 512 and 498 EMCs were quantitated in two cohorts, respectively. Both univariate linear regression with false discovery rate (FDR), and pathway enrichment analyses using a global association test were performed. At the pre‐CY time point, no EMCs were associated at FDR less than 0.1. At pre‐HCT, cohort 1 had one EMC (levoglucosan) survive the FDR threshold. At pre‐graft, cohort 1 and cohort 2 had 20 and 13 EMCs, respectively, exhibiting unadjusted p values less than 0.05, with the only EMCs having an FDR less than 0.1 being two unknown EMCs. At 24‐h post‐CY, there were three EMCs, two ketones, and threitol, at FDR less than 0.1 in cohort 2. These results demonstrate the potential of pharmacometabonomics, but future studies in larger samples are needed to optimize CY.

Study Highlights
  • WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
We report the first pharmacometabonomic study of the association of plasma EMCs with cyclophosphamide pharmacokinetics, specifically the ratio of 4HCY/CY AUC.
  • WHAT QUESTION DID THIS STUDY ADDRESS?
This study addresses the question regarding if EMCs in the plasma before PT‐CY administration are associated with the ratio of 4HCY/CY AUC.
  • WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
This study adds to our knowledge that longitudinal collection of plasma EMC samples is feasible in HCT patients receiving PT‐CY. In addition, the plasma EMC changes over the ~21‐day time period that starts pre‐HCT to 24‐hr after the first PT‐CY dose.
  • HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
This study demonstrates the possibility of pharmacometabolomic research to evaluate the pharmacokinetics of a drug – in this case, cyclophosphamide – with a complex pharmacokinetic disposition.  相似文献   
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Background and aimsCholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM.Methods and results57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA.A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP.ConclusionExogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.  相似文献   
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17 serum samples from cats after surgery operations in one of veterinary clinic in Olsztyn have been examined. The study on anti-Toxoplasma gondii immunoglobulin IgG presence was carried out by direct agglutination method using the Toxo-Screen DA test. 70.6% positive samples in 1:40 titration, 58.8% in 1:4000 titration and 5.9% questionable result in both dilutions were obtained.  相似文献   
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Introduction: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor of VEGFR1,2,3,4, FGFR1,2,3,4, PDGFR-α as well as RET and KIT signaling network. Its activity against radioiodine-resistant differentiated thyroid cancer (DTC) has been recently demonstrated. Patients, who were given lenvatinib, showed significantly longer median progression free survival than placebo group, 18.3 vs 3.6 months, respectively. This review is focused on lenvatinib safety profile in patients treated due to DTC and medullary thyroid carcinoma. Among the most frequent lenvatinib-related adverse events (AEs) were hypertension, proteinuria, diarrhea, appetite decrease, weight loss, nausea and stomatitis. Although a lot of them were manageable, in 35–68% of patients dose reduction was required. Nevertheless, only 15% of subjects withdrew the drug due to its toxicity.Areas covered: published results of clinical trials phase II and III investigating both safety and efficacy of lenvatinib in thyroid cancer.Expert opinion: Lenvatinib shows acceptable safety profile in patients with thyroid carcinoma. Treatment-related side effects are usually manageable by dose modifications or by concomitant non-pharmacological and pharmacological treatment. However, the early recognition of any potential drug toxicity is crucial to avoid serious complications as well as to keep a patient on drug as long as the treatment is beneficial.  相似文献   
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