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Metabolism of immunosuppressants in children with inflammatory bowel disease
Pospíšilová, Kristýna ; Bronský, Jiří (advisor) ; Leníček, Martin (referee) ; Dědek, Petr (referee)
Metabolism of immunosuppressants in children with inflammatory bowel disease Abstract Thiopurines are still used as the main immunosuppressants in the maintenance therapy of paediatric Crohn's disease. According to official guidelines, in case of failure, biological therapy (mainly infliximab or adalimumab) is generally commenced. The present thesis focuses on the possibilities of therapy optimization in children in whom the conventional Crohn's disease therapy has failed based on the metabolism of administered immunosuppressive medications. We confirmed that the knowledge of thiopurine metabolites concentration in red blood cells may help to monitor patients' adherence to therapy. However, according to our observations in children on combination therapy of infliximab and thiopurine lower concentrations of 6- thioguanine (the active metabolite of thiopurines) seems to be effective compared to what has been expected. We presented a web application designed to partially substitute for the thiopurine metabolite measurements based on easily available laboratory data. Last, but not least, we confirmed that the clinical effect and safety profile of both adalimumab and infliximab are similar in the treatment of paediatric Crohn's disease. Only in case of family history of atopic dermatitis adalimumab may be preferred.
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Electrochemical determination of 6-thioguanine at boron doped diamond film electrod
Humpolíková, Jiřina ; Fischer, Jan (advisor) ; Schwarzová, Karolina (referee)
This master's thesis is focused on the determination of 6-thioguanine (6-T) by DC voltammetry (DCV), differential pulse voltammetry (DPV) and flow injection analysis with electrochemical detection (FIA-ED) on a boron doped diamond electrode (BDDFE). The optimum conditions for determination of 6-T were found and under these conditions, concentration dependences were measured and the limits of quantification (LOQ) were calculated for each method. Medium of 60% methanol and phosphate buffer (PB) pH 2,0 was chosen as optimum for DCV and DPV determination of 6-T at BDDFE. For both DCV and DPV, the linear concentration dependences were obtained in concentration ranges of 6-T from 2 µmol·l-1 to 10 µmol·l-1 with LOQ 0,9 µmol·l-1 for DCV and 1,5 µmol·l-1 for DPV. Lower LOQ was achieved in PB pH 2,0, where LOQ was 0,6 µmol·l-1 for both DCV and DPV, but the problem was lower repeatability. In PB pH 2 6-T was determined by DCV in drinking and river water with LOQ 1,3 µmol·l-1 in both drinking and river water. The possibility of solid phase extraction was investigated as a method for preliminary separation of 6-T from urine. For FIA under optimized conditions (polarization potential 1300 mV, flow rate 5 ml·min1 and sample volume 50 µl) the linear concentrations dependences were obtained in concentration ranges...
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Electrochemical determination of 6-thioguanine at boron doped diamond film electrod
Humpolíková, Jiřina ; Fischer, Jan (advisor) ; Schwarzová, Karolina (referee)
This master's thesis is focused on the determination of 6-thioguanine (6-T) by DC voltammetry (DCV), differential pulse voltammetry (DPV) and flow injection analysis with electrochemical detection (FIA-ED) on a boron doped diamond electrode (BDDFE). The optimum conditions for determination of 6-T were found and under these conditions, concentration dependences were measured and the limits of quantification (LOQ) were calculated for each method. Medium of 60% methanol and phosphate buffer (PB) pH 2,0 was chosen as optimum for DCV and DPV determination of 6-T at BDDFE. For both DCV and DPV, the linear concentration dependences were obtained in concentration ranges of 6-T from 2 µmol·l-1 to 10 µmol·l-1 with LOQ 0,9 µmol·l-1 for DCV and 1,5 µmol·l-1 for DPV. Lower LOQ was achieved in PB pH 2,0, where LOQ was 0,6 µmol·l-1 for both DCV and DPV, but the problem was lower repeatability. In PB pH 2 6-T was determined by DCV in drinking and river water with LOQ 1,3 µmol·l-1 in both drinking and river water. The possibility of solid phase extraction was investigated as a method for preliminary separation of 6-T from urine. For FIA under optimized conditions (polarization potential 1300 mV, flow rate 5 ml·min1 and sample volume 50 µl) the linear concentrations dependences were obtained in concentration ranges...
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