|
|
Observation of human sperm cell immunogenic properties
Cibulka, Jan ; Ulčová-Gallová, Zdeňka (advisor) ; Fingerová, Helena (referee) ; Madar, Jindřich (referee) ; Šíma, Petr (referee)
The issue of human infertility is becoming increasingly pressing, especially in so- called industrially developed countries. Formally, we can share the infertility attributes between the male and the female partner (as a male and female infertility factor), but the problem finally affects the whole parental couple. Perhaps, due to the complexity of the female reproductive tract, it is estimated that over 40% of the reproductive failure is hidden in one or more of its parts. The "strong point" of the male factor is derived from the pathological sperm count. For the remaining 15 to 20% of causes, whether morphological or functional, cannot be to find either clearly or not at all. We talk about the otherwise unexplained infertility, that can be caused in up to 30% immunologically. Due to broad concept of immunology of reproduction, we have chosen literally as a probe into this issue in all respects unique spermatic cell that represents not only a carrier of genetic information, but also a set of antigenic structures. This cell seems to be perfect for this task, because of its availability to most basic laboratory techniques. We will try to familiarize ourselves with some of the obstacles that may prematurely end its mission, especially with the antibodies against its antigenic structures (ASA -...
|
|
|
Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Protein in the Placenta: Expression, Localization and Function
Ahmadimoghaddam, Davoud ; Štaud, František (advisor) ; Trejtnar, František (referee) ; Večeřa, Rostislav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Davoud Ahmadimoghaddam Supervisor Prof. PharmDr. František Štaud, Ph.D. Title of Doctoral Thesis Organic Cation Transporter 3 (OCT3/SLC22A3) and Multidrug and Toxin Extrusion 1 (MATE1/SLC47A1) Protein in the Placenta: Expression, Localization and Function. The aim of the present study was to investigate the expression, localization, and function of organic cation transporter 3 (OCT3, Slc22a3) and multidrug and toxin extrusion protein 1 (MATE1, Slc47a1) in the rat placenta. Using qRT-PCR, Western blotting and immunohistochemical techniques, we demonstrated abundant expression of OCT3 on the basolateral, i.e., fetus-facing side of the placenta, and MATE1 on the apical, i.e., maternal side of the placenta. To investigate the role of these transporters in the transplacental pharmacokinetics, the in situ method of dually perfused rat term placenta was employed in open- and closed-circuit arrangements; 1-methyl-4-phenylpyridinium (MPP+) was used as a model substrate of both OCT3 and MATE1. We provide evidence that OCT3 and MATE1 cause considerable asymmetry between maternal-to-fetal and fetal-to-maternal transport of MPP+ in favor of fetomaternal direction. Using closed- circuit...
|
|
|
Molecular modelling in drug development
Kolář, Michal ; Hobza, Pavel (advisor) ; Vondrášek, Jiří (referee) ; Clark, Tim (referee)
Molecular modelling has become a well-established tool for studying biological mole- cules, moreover with the prospect of being useful for drug development. The thesis summarises research on the methodological advances in the treatment of molecular flexibility and intermolecular interactions. Altogether, seven original publications are accompanied by a text which aims to provide a general introduction to the topic as well as to emphasise some consequences of the computer-aided drug design. The molecular flexibility is tackled by a study of a drug-DNA interaction and also by an investigation of small drug molecules in the context of implicit solvent models. The approaches which neglect the conformational freedom are probed and compared with experiment in order to suggest later, how to cope with such a freedom if in- evitable. The noncovalent interactions involving halogen atoms and their importance for drug development are briefly introduced. Finally, a model for a faithful description of halogen bonds in the framework of molecular mechanics is developed and its per- formance and limits are tested by a comparison with benchmark ab initio calculations and experimental data. 1
|
|
|
Transplantace kostní dřeně příjemcům s regenerující krvetvorbou: účinnost transplantace a stav regenerující kostní dřeně
Forgáčová, Katarína ; Nečas, Emanuel (advisor) ; Vávrová, Jiřina (referee) ; Hofer, Michal (referee)
Hematopoietic stem cells (HSCs) have the ability of both self-renewal and differentiation. After bone marrow damage, surviving host HSCs or transplanted donor HSCs are able to restore hematopoiesis and maintain it for a long time due to the self-renewal potential. HSCs reside in a specific microenvironment in the bone marrow, in stem cell niche, which supports their survival and controls their functioning. In this study, we investigated the impact of bone marrow damage induced by increasing doses of irradiation on engraftment efficiency of transplanted donor repopulating cells. Using the CD45.1/CD45.2 congenic mouse model, we developed a new approach enabling estimation of surviving HSCs in damaged hematopoietic tissue. Its principle is in measuring of the donor chimerism resulting from transplantation of a defined dose of normal congenic bone marrow cells. The transplanted donor cells contain repopulating cells, progenitors (STRCs) and HSCs (LTRCs) that give rise to blood cell production which proceeds in parallel with that present in the host hematopoietic tissue. We applied this approach to monitor spontaneous regeneration of repopulating cells, including HSCs, in mice irradiated with a sublethal dose of 6 Gy or by a lethal dose of 9 Gy and rescued by syngenic bone marrow cells. This was...
|
|
|
Production of heterologous proteins in plants - human papillomavirus (HPV 16) derived antigens
Folwarczna, Jitka ; Čeřovská, Noemi (advisor) ; Ryšánek, Pavel (referee) ; Kumar, Jiban (referee)
5 Abstract Even though prophylactic vaccine against human papillomavirus (HPV) is currently licensed, infections by the virus continue to be the major health problem mainly in developing countries. Considerable effort is being devoted to preparation of therapeutic vaccine and to decrease of the production costs of current vaccine. Viral proteins such as the E7 oncoprotein and the L2 capsid protein from HPV type 16 are promising targets for the development of the experimental anti-HPV vaccine. The aim of our work was optimization of expression of mutagenized E7 oncoprotein (E7ggg) fused to the C-terminus of Tobacco mosaic virus (TMV) coat protein (CP) or Potato virus X (PVX) CP in viral vectors derived from these plant viruses. The impact of linkers connecting CP and E7ggg fusion partners on expression and stability of fusion proteins was examined. The fusion proteins were first expressed in Escherichia coli (E. coli) MC1061 to assess the characteristics of the recombinant protein prior to their transient expression in both non-transgenic or transgenic Nicotiana benthamiana (N. benthamiana). We have obtained the high level expression in E. coli, but most of the expressed proteins based on TMV CP remained in insoluble inclusion bodies. To increase the ratio of soluble protein various molecular...
|
|
|
Soviet Near East Policy 1917 - 1921 between Revolution and Pragmatism
Novák, Petr ; Litera, Bohuslav (advisor) ; Reiman, Michal (referee) ; Gombár, Eduard (referee)
This work addresses the beginnings of Soviet policy towards the Middle Eastern countries Afghanistan, Persia, and the Ottoman Empire/Turkey between 1917 and 1921. The author addresses the manner in which Soviet leaders formed their perceptions of the Middle East and the place and role assigned to the countries in question by Soviet leaders. At the same time, the work investigates how real Soviet policy towards the countries mentioned above was formulated, what the aims and motivations of the policy were, and the factors which influenced its formulation and realization.
|
|
|
Antiproliferative, antioxidant and anti-inflammatory activity of quinones, terpenoids and their derivatives
Přibylová, Marie ; Vaněk, Tomáš (advisor) ; Smrček, Stanislav (referee) ; Hájek, Miroslav (referee)
Plant compounds play an important role in human medicine. They are a source of new drugs or serve as an inspiration for drugs' development. This thesis presents a study about syntheses of derivatives and biological activities of two groups of natural products, quinones and terpenoids. Terpenoids are plant secondary metabolites which are known for their antimicrobial, anti-inflammatory and anti-tumoral activities. We have focused on two representatives, paclitaxel and carvacrol. GnRH-paclitaxel anti-tumor conjugates potentially suitable for targeted delivery to cancer cells were prepared. Their antiproliferative activities in vitro were evaluated on MCF-7 cancer cell line and cytotoxicity in rat hepatocytes. Carvacrol and its derivative were tested for its possible anti- inflammatory effect, which was assessed in vitro as their potential to inhibit prostaglandin E2 biosynthesis via cyclooxygenase pathway. Quinones, other targets of the thesis, are well-known for biological activities similar to terpenoids. Thymoquinone, juglone and their derivatives were tested in vitro as inhibitors of cyclooxygenases and 5-lipoxygenase. Derivatives of juglone were prepared to help us to suggest structure-activity relationship of this compound. Thymoquinone and its derivatives were evaluated for their antioxidant capacity...
|
|
|
Sexual dysfunctions in w omen with urinary incontinence
Pastor, Zlatko ; Weiss, Petr (advisor) ; Halaška, Michael (referee) ; Raboch, Jiří (referee)
Aim: This study was designed to examine the influence of female urinary incontinence on development of sexual dysfunctions. By means of the questionnaire investigation we inquired how often and how the sexual behaviour and response were modified. Our goal was to determine the prevalence of coital incontinence, describe the most common sexual disorders and to find out how women deal with the urinary incontinence in a partner relationship and how such situations are resolved. Attention was given to the interests of health care professionals in this area, the quality of their communication with patients, effect and satisfaction with therapy. Research sample: The study included 106 women with urinary incontinence (aged 30-44 years and 44-59 years). Characteristics of their sexual behaviour were compared between the two age groups and in relation to assessed diagnosis. Changes in sexual behaviour were evaluated both in relation to the population group who were a part of representative research study of Czech women in 2008 and control group of 112 healthy women of comparable age. Material and methods: To describe and analyze sexual dysfunction in incontinent women, we used a modified version of sexological questionnaire from the research study of Weiss and Zverina and two international validated...
|
|
|
Synthesis and Design of Potentially Antibacterial Active Compounds
Kozic, Ján ; Vinšová, Jarmila (advisor) ; Doležal, Martin (referee) ; Hanusek, Jiří (referee)
University: Charles University in Prague Faculty: Faculty of Pharmacy in Hradec Králové Department: Department of Inorganic and Organic Chemistry Candidate: Ing. et Mgr. Ján Kozic Supervisor: Prof. RNDr. Jarmila Vinšová, CSc. Title of Doctoral Thesis: Synthesis and Design of Potentially Antibacterial Active Compounds This work deals with the synthesis of benzanilides and their analogues as the potentially antimycobacterial active compounds. In the theoretical part of the work there is a description of tuberculosis (TBC) as a mycobacterial infectious disease and a short characteristic of recent antituberculotic drugs. The most important features of both, which determine the imperfection of recent antitubeculotics and the long-term multidrug TBC treatment, are emphasised. Further, some of the potential targets, useful for the development of new and more effective antituberculotics, are reviewed. Finally, there is a short overview of biological properties of benzanilides and thiobenzanilides and a more in depth characteristic of stereochemical properties of these compounds. In the experimental part of the work there are presented 100 benzanilide derivatives and their analogues. Ninety-two of these compounds are original, which have not been described in literature yet. For all of the compounds there...
|
|
|
Military-political Aspects of Soviet Invasion Of CSSR in August 1968
Čížek, Martin ; Reiman, Michal (advisor) ; Tůma, Oldřich (referee) ; Kudrna, Ladislav (referee)
The aim of the dissertation is to explain the military-political reasons behind the long-term attempt of the Soviet Union to deploy its units on Czechoslovak territory, as well as the root cause of the military operation against Czechoslovakia which was carried out by the five member armies of the Warsaw Pact. One of the main reasons for this was the military and strategic situation in Central Europe in the 1960's, and also the issue of nuclear weapons and their carriers. A separate chapter is dedicated to Soviet attempts to deploy its units on Czechoslovak territory prior to Operation Danube. The final chapter deals with the reorganization of the CPA, the establishment of the CGV and the NATO reaction to the change in the strenght of armed forces present on the border of the two Blocs.
|
guest ::
RSS feed.