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Acyclovir release from branched oligoesters
Vondráčková, Hana ; Šnejdrová, Eva (advisor) ; Dittrich, Milan (referee)
11 Summary The objective of this graduation thesis was a description of a liberation of aciclovir from plastificated oligoesters drug carriers. We used terpolymers of D,L-lactic acid, glycolic acid and dipentaerythritol or tripenaterythritol [LA/GA/D(T)]. Theoretic part is devote to processes during a liberation of a medicament from a polymer carrier also to polyesters of lactic acid, glycolic acid and their copolymers who have a remarkable impact in the field of controlled drug delivery and as well to pentaerythritol. At the experimental section we used disolution tests in order to obtain a concentration of released aciclovir by spectrophotometry. Process of liberation was diagrammatized like a dependence of cumulative precentage of released drug at a time. The results indicate that the carrier 3T is the best drug delivery vehicle for aciclovir. 3T is disposing the highest factor of branching and it has the biggest molar weight.
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Evaluation of transdermal permeability of folic acid using methylparaben as marker.
Kubíková, Kateřina ; Berka, Pavel (advisor) ; Doležal, Pavel (referee)
In the theoretical part, there is briefly described the problematic of skin in the connection with transdermal permeability of substances. This part is followed by a general summary about transdermal permeability testing. Further on there were described the basic features of methylparaben and folic acid as substances used for permeability tests. Experimental part of the diploma thesis describes the testing conditions for in vitro testing of permeability of methylparaben and folic acid from the TRIS buffer, the TRIS buffer with propylene glycol (PG) (3:2), isopropyl myristate (IPM) and isopropyl myristate (IPM) with parafin oil (PO) (2:3) through the full thickness pig ear skin. Measured values of normalized fluxes of folic acid JKLn were as follows: from TRIS buffer: 1,00 ± 0,47, RSD 46,5%; from TRIS buffer with PG: 0,28 ± 0,11, RSD 40,1%; from IPM: 0,86 ± 0,72, RSD 83,4%; from IPM and PO: 2,08 ± 3,91, RSD 188,2%. The following average ratios of folic acid normalized fluxes and methylparaben normalized fluxes JKLn/JMPn from separate donors (and their standard devations and relative standard deviations) were obtained: from TRIS buffer: 0,98 ± 0,46, RSD 46,3%; from TRIS buffer with PG: 0,18 ± 0,09, RSD 52,2%; from IPM: 0,78 ± 0,77, RSD 98,9%; from IPM and PO: 1,76 ± 2,86, RSD 162,4%. The conclusion...
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Late effect of perinatal hypoxia and pleiotropic effect of statins on acute ischemia-reperfusion myocardial injury
Malý, Jiří ; Pirk, Jan (advisor) ; Kittnar, Otomar (referee) ; Pudil, Radek (referee)
Background: In last decades there were many experimental interventions protecting myocardium against ischemia but aside from early reperfusion none of them was successfully adopted in clinical practice. In our experimental work we try to apply clinical situations into an experimental condition to find out feasible solution how to influence tolerance of myocardium to ischemia. We choose two actual clinical settings: 1. congenital cyanotic heart defects and 2. hypercholesterolemia chronically treated with statins Aim: To examine: 1. the effect of of perinatal hypoxia to the tolerance of the adult myocardium to acute ischaemia/reperfusion injury with regard to sex; 2. the effect of the acute and chronic statin treatment on the tolerance of the adult rat myocardium to ischemia. (...) The effect of perinatal hypoxia on myocardial infarct size in adult males and females was not demonstrated. 2. Acute administration of statin to rats in vivo significantly decreased infarct size expressed as IS/LV, in comparison to infarct size expressed as IS/AR the protective effect of statin administration was suggested, but did not reach statistical significance. Acute administration of statin during reperfusion significantly reduced the contractile dysfunction. However, this protective effect of statins was not present after...
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The Role of Uncoupling in Down-regulation of Reactive Oxygen Species
Ježek, Jan ; Žáčková, Markéta (advisor) ; Modrianský, Martin (referee) ; Drahota, Zdeněk (referee)
Uncoupling attenuates Complex I-derived superoxide production by accelerating electron flux and proton pumping within Complex I. However, under circumstances leading to hampered proton pumping pathway within Complex I, e.g. due to aberrant mutations of mtDNA encoding either ND2, ND4 or ND5 Complex I H+-pumping subunit, therapeutic strategy based simply on uncoupling would fail. Experimentally, hydrophobic amiloride EIPA mimicks the model of disabled H+-pumping. We show for the first time that EIPA is a real inhibitor of H+-pumping of mitochondrial Complex I. We searched for an agent that, unlike uncoupling, would be able to counteract oxidative stress associated with obstructed proton pumping of Complex I. Mitochondria-targeted ubiquinone MitoQ10 proved to be an effective antioxidant for this purpose when the rate of superoxide formation was high due to the electron flow retardation within Complex I. Because of its pro-oxidant properties, targeted delivery of MitoQ10 as a cure to the pathological tissue is necessary. Activation of mitochondrial phospholipase iPLA2 by mild oxidative stress can provide free fatty acid hydroperoxides as the cycling substrates for UCP2 that initiates mild uncoupling leading to the attenuation of reactive oxygen species (ROS) production, as a part of feedback regulatory loop of...
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Mechanismy průniku sylicylátů monovrstvami buněk Caco-2: zapojení transportních proteinů.
Čierný, Jakub ; Doležal, Pavel (advisor) ; Šnejdrová, Eva (referee)
The aim of this work is to study properties of the transport of salicylic acid and its derivates across Caco-2 cell monolayers, an influence of possible inhibitors of cell transportation and a brief review of related issues. The influence of substance, which opens tight junctions between Caco-2 cells, so called absorption enhancers, is also examined. The main goal is to find out, what kind of transport takes the main part in salicylic acid transport and to compare the results to the data obtained using gentisic and 5-hydroxyisophthalic acid, and, at the same time, to study the influence of ethylenediaminetetraacetic acid as an absorption enhancer and to compare possible inhibitive effect of several compounds. It was assumed that both passive and active transport take part in the transport of salicylic acid. The theoretical part of the thesis briefly summarizes chemical substances properties, which have an influence on their transport across cell membranes, introduces Caco-2 cells as an important instrument of drug absorption and distribution research, defines the individual types of cell transports and describes the types of transporter proteins which can be localized on the Caco-2 cell membrane. The experimental part of the work describes the technique of Caco-2 cells cultivation and the process of...
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Oligoester matrices with antimicrobial drugs II.
Kapiasová, Jana ; Šnejdrová, Eva (advisor) ; Dittrich, Milan (referee)
Jana Kapiasová Diploma Thesis 2006 The objective of this graduation thesis was a description of a liberation of acyclovir and terbinafine from plasticized oligoesters drug carriers. The terpolymers of D,L-lactic acid, glycolic acid and dipentaerythritol or mannitol [LA/GA/D(M)] were used as carriers of the drugs. Theoretic part is devoting to characteristics of the polyesters, mechanism of the hydrolytic degradation and importance of the citrate plasticizers. At the experimental section we used dissolution tests in order to obtain a concentration of released model drugs by spectrophotometer. Process of liberation was diagrammatized like a dependence of cumulative percentage of released drug at a time. The results indicate that fluconazol was released from carriers 3M and 8D fluconazol very fast, during 24 hours. On the other hand realising or the fluconazol from carriers 5M and 3D was very slow for the 8 days. Despite of the complete degradation the matrices during the dissolution test, there was no terbinafine determined in the dissolution liquid. It will be necessary to use different analytical method.
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Effect of feeding MDOCTM the atherogenic process in experimental / / model of atherosclerosis.
Tomalová, Pavla ; Nachtigal, Petr (advisor) ; Kopecký, Martin (referee)
Influence of MDOCTM Administration on Atherogenic Process in the Experimental Model of Atherosclerosis. Mgr. Pavla Tomalová In this study we investigated prospective hypolipidemic and anti - inflammatory effects of modified oxidized cellulose (MDOC). In the therapy of hyperlipidemia and blood - vessel complications (atherosclerosis) there are used the most considerable substances - statins, today. However, it was also documented, that feed dietary roughage has positive influence on cardiovascular system, inclusive of cholesterol level. MDOC (polyanhydroglucuronic acid), because of it's properties can be classified probably as the soluble fibre. We used apoE deficient mice as the model of atherosclerosis, fed by atherogenic diet. We analyzed levels of total cholesterol and other lipoprotein fractions and serum concentrations of inflammatory markers (IL-6 and VCAM-1) in blood. Total cholesterol concentrations were assessed enzymatically by conventional diagnostic methods and spectrophotometric analyses. For the detection of VCAM-1 expression in aortic sinus and part of aortic arch we used imunohistochemical methods and for quantification of VCAM-1 expression we used stereological methods. Biochemical analyses results showed that MDOC administration did not affect levels of total cholesterol, VLDL cholesterol,...
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Effect of administration of drugs from the group of statins on the atherogenic process / / in an experimental model of atherosclerosis.
Koutníková, Jitka ; Nachtigal, Petr (advisor) ; Trejtnar, František (referee)
The effects statins administration on atherogenic process in the experimental model of atherosclerosis. Mgr. Jitka Koutníková The aim of this rigorous work was to detect and quantify the changes of endothelial expression of VCAM - 1 (the marker of endothelial dysfunction) and endoglin (the marker of angiogenesis) in vessel wall of apoE deficient mice. Endoglin is a part of the receptor complex of the transformation growing factor beta (TGF - beta). Statins are the most considerable substances for the treatment of hyperlipidemia and blood - vessel complications (atherosclerosis). Statins decrease levels of LDL cholesterol and also of triglycerides. Moreover, pleiotropic effects take important part in statin's benefit: the decrease of activity of inflammatory and prothrombotic processes. We used apoE deficient mice as the model of atherosclerosis, fed by standard laboratory diet. We analyzed the levels of total cholesterol in blood and we observed expression of VCAM - 1 and endoglin in aortic sinus and part of aortic arch in all mice. Total cholesterol concentrations were assessed enzymatically by conventional diagnostic methods and spectrophotometric analyses. To display VCAM-1 and endoglin expression in aortic sinus and part of aortic arch we used imunohistochemical methods and for quantification of VCAM-1...
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Separation and determination of pharmaceutically important compounds using electrophoretic methods
Hamoudová, Rafífa ; Pospíšilová, Marie (advisor) ; Nobilis, Milan (referee) ; Jokl, Vladimír (referee)
This thesis deals with the use of electrophoretic methods in the analysis of pharmaceutically important compounds. In the theoretical part, the classification of capillary electrophoretic techniques is discussed. Capillary zone electrophoresis (CZE, capillary isotachophoresis (ITP), micellar elektrokinetic chromatography (MEKC), microemulsion elektrokinetic chromatography (MEEKC), isoelectric focusation (IEF), capillary electrochromatography (CEC) and capillary gel electrophoresis (CGE) are described. Further, on-line pre-concentration methods are described. Particular attention is given to the on-line combination of capillary isotachophoresis with capillary zone electrophoresis using column coupling arrangement. This combination enables the improvement of the selectivity of separation and the improvement of the limit of detection of analytes present in complex matrices of biological and environmental origin. Afterwards, the results of the experimental analyses are presented: 1. The first paper deals with the use of CZE in the analysis of ibuprofen and flurbiprofen in pharmaceuticals. Separation was carried out in a fused silica capillary (60 cm x 100 m I.D effective length 45 cm) at 30 kV with UV detection at 232 nm. The optimized background electrolyte was 20mM N-(2- acetamido)-2-aminoethanesulfonic acid...
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Allooimmunosensitization in left ventricular assist device recipients and impact on post-transplantation outcome
Urban, Marián ; Netuka, Ivan (advisor) ; Ošťádal, Petr (referee) ; Mrázek, František (referee)
Background: In recent years mechanical circulatory assist devices became an established option in bridging patients with refractory heart failure to heart transplantation. One of the alleged limitations of mechanical devices is a high degree of antibody production with possible deleterious effect on subsequent heart transplantation outcome. Aim: The main goal of this study is to assess the role of antibodies on the outcome of surgical treatment of patients with end- stage heart failure. Method: Firstly, we present a literature review on the current state of knowledge of possible immunologic mechanisms involved in antibody production in left ventricular assist device (LVAD) recipients, new methods of antibody detection, desensitization strategies and overview of published evidence assessing the impact of sensitization on post-transplantation outcome. In the experimental part of our study we prospectively evaluated the presence of anti-Angiotensin II Type 1 Receptor (AT1R) antibodies in 83 Heart Mate II (HMII) recipients who were implanted at our institution between 2008 and 2012 and survived the first 60 days. On-device survival and device malfunction, major infection, major bleeding and neurologic dysfunction were compared between antibody positive and antibody negative recipients. Out of a total...
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