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NORTRIPTYLINE HYDROCHLORIDE TRANSDERMAL DELIVERY FROM HMPC PATCH: EFFECT OF CONCENTRATION
Heřmanová, Ivana ; Doležal, Pavel (advisor) ; Berka, Pavel (referee)
1. ABSTRACT The objective of this study is to optimize a nortryptiline hydrochloride patch previously designed (1) with the intended aim to develop controlled drug release system as a smoking cessation aid. Patches of 5%, 7.5% and 10% NTH concentrations were assayed for physical experiments. Measured thickness of the patches remains constant regardless of the NTH concentration. Obtained values are 31.88±5.0 µm, 32.33±5.1 µm and 32.00±3.8 µm for 5%, 7.5% and 10% patch respectively. The variability is lower than 20 % in every case. Release and penetration studies were performed using Franz type of diffusion cells. The maximum cumulative amount released from assayed patches at 7 hours (last sampling point) varies as a function of the NTH concentration. Two kinetic models, power law and first order kinetics, are useful in order to predict the maximum amount to be released and the rate at which the process will be developed. Taking first order results into account, the maximum amount to be released (Qinf) is 7.185±0.30[mg/cm2 ]; 12.359±0.69[mg/cm2 ]; and 29.333 ±1.97 [mg/cm2 ] for 5%; 7.5% and 10%patch respectively. Considering the power law fitting, the main conclusion is that the release mechanism is basically fickian diffusion as the exponent is about 0.5. Estimated permeation parameters are Kp=0.019·10-3...
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The mechanism of action of L-asparaginase in childhood acute lymfoblastic leukemia
Heřmanová, Ivana ; Starková, Júlia (advisor) ; Šálek, Cyril (referee) ; Trbušek, Martin (referee)
Acute lymphoblastic leukemia (ALL) is the most frequent type of childhood cancer. The key component in the therapy, L-asparaginase (ASNase), hydrolyzes plasma asparagine and glutamine. Leukemic cells are sensitive to the depletion due to low activity of asparagine synthetase. Although the treatment is very effective, resistance and side effects remain a serious problem in some cases and its mechanism of action is not well understood. In this study, we wanted to elucidate the effect of ASNS expression level on the sensitivity of ALL cells to ASNase treatment. Our aim was also to clarify the intracellular consequences of the amino acid depletion to define the reason of different patients' response. We used four ALL cell lines (NALM-6, RS4;11, REH, and UOCB-6) and 30 diagnostic bone marrow samples of ALL patients to study the relationship between ASNS expression and sensitivity to ASNase using MTS proliferation assay. RNA interference was used to study the effect of a range of ASNS levels on the response to ASNase treatment. Using a cell line model with a gradually knocked-down ASNS gene, we defined a cutoff level below which ASNS gene expression does not correlate with sensitivity to ASNase. Importantly, ASNS gene expression in patients' ALL blasts is below this level. We confirmed that there was no...
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The mechanism of action of L-asparaginase in childhood acute lymfoblastic leukemia
Heřmanová, Ivana ; Starková, Júlia (advisor) ; Šálek, Cyril (referee) ; Trbušek, Martin (referee)
Acute lymphoblastic leukemia (ALL) is the most frequent type of childhood cancer. The key component in the therapy, L-asparaginase (ASNase), hydrolyzes plasma asparagine and glutamine. Leukemic cells are sensitive to the depletion due to low activity of asparagine synthetase. Although the treatment is very effective, resistance and side effects remain a serious problem in some cases and its mechanism of action is not well understood. In this study, we wanted to elucidate the effect of ASNS expression level on the sensitivity of ALL cells to ASNase treatment. Our aim was also to clarify the intracellular consequences of the amino acid depletion to define the reason of different patients' response. We used four ALL cell lines (NALM-6, RS4;11, REH, and UOCB-6) and 30 diagnostic bone marrow samples of ALL patients to study the relationship between ASNS expression and sensitivity to ASNase using MTS proliferation assay. RNA interference was used to study the effect of a range of ASNS levels on the response to ASNase treatment. Using a cell line model with a gradually knocked-down ASNS gene, we defined a cutoff level below which ASNS gene expression does not correlate with sensitivity to ASNase. Importantly, ASNS gene expression in patients' ALL blasts is below this level. We confirmed that there was no...
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Pragmatic and Stylistic Analysis of the Horoscopes in Periodicals
Heřmanová, Ivana ; Chejnová, Pavla (advisor) ; Janovec, Ladislav (referee)
The thesis entitled "Pragmatic and stylistic analysis of the horoscopes in periodicals" deals with the horoscopes from linguistic point of view; the greatest attention is paied to the pragmatic and stylistic aspects. The goal of the thesis is to identify the typical features of horoscopes on the basis of pragmatic and stylistic analysis. The research material comprises of 1752 astrological predictions taken from sixteen different periodicals. The author and the recipient of horoscope are characterized in each chapter and selected attributes of the target group are studied in each chapter as well - age, gender, social roles and status. It is dealt with the intention of horoscopes; its impact on recipient and strategies used by authors of horoscopes are analyzed too. The thesis presents the way vocabulary and other language tools are used in horoscopes to communicate intention of their authors. The analysis also deals with themes of horoscopes.
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NORTRIPTYLINE HYDROCHLORIDE TRANSDERMAL DELIVERY FROM HMPC PATCH: EFFECT OF CONCENTRATION
Heřmanová, Ivana ; Doležal, Pavel (advisor) ; Berka, Pavel (referee)
1. ABSTRACT The objective of this study is to optimize a nortryptiline hydrochloride patch previously designed (1) with the intended aim to develop controlled drug release system as a smoking cessation aid. Patches of 5%, 7.5% and 10% NTH concentrations were assayed for physical experiments. Measured thickness of the patches remains constant regardless of the NTH concentration. Obtained values are 31.88±5.0 µm, 32.33±5.1 µm and 32.00±3.8 µm for 5%, 7.5% and 10% patch respectively. The variability is lower than 20 % in every case. Release and penetration studies were performed using Franz type of diffusion cells. The maximum cumulative amount released from assayed patches at 7 hours (last sampling point) varies as a function of the NTH concentration. Two kinetic models, power law and first order kinetics, are useful in order to predict the maximum amount to be released and the rate at which the process will be developed. Taking first order results into account, the maximum amount to be released (Qinf) is 7.185±0.30[mg/cm2 ]; 12.359±0.69[mg/cm2 ]; and 29.333 ±1.97 [mg/cm2 ] for 5%; 7.5% and 10%patch respectively. Considering the power law fitting, the main conclusion is that the release mechanism is basically fickian diffusion as the exponent is about 0.5. Estimated permeation parameters are Kp=0.019·10-3...
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