|
|
Attitudes and experience of the university students with drugs of abuse
Stejskalová, Lucie ; Pávek, Petr (advisor) ; Višňovský, Peter (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ ATTITUDES AND EXPERIENCE OF STUDENTS WITH ADDICTIVE SUBSTANCES: Attitudes of the third year undergraduate pharmacy students of Charles University in Hradec Králové towards the alcohol and tobacco Lucie Stejskalová This thesis investigates the attitudes, experience and knowledge of the third year undergraduate pharmacy students of Charles University in Hradec Králové in academic year 2005/2006 to legal addictive substances - alcohol and tobacco. It contains both theoretical and practical part. Theoretical part covers basic terms, possible reasons for students' drugs abuse, possibilities of drug addiction prevention, kinds of drug addiction and more detailed pharmacological information about alcohol and tobacco. The practical part is focused on anonymous questionnaire results interpretation. In the conclusion the recent results are being compared with the results of the similar study which was executed in the year 2000 at the same faculty. Gathered information is also collated with the results coming from different faculties (Prague and Brno) and ESPAD study. There were 190 students who took part in this research. The age interval ranged from 21 to 23 years and the mean age was 22.0 years. My study proves that most students have experience...
|
|
|
Combination treatment of tumour cell culture with miRNA mimetics and oncogene targeted siRNAs.
Šabouková, Martina ; Miletín, Miroslav (advisor) ; Pávek, Petr (referee)
During the last two decades, the attention of many scientists has been attracted by a newly discovered group of regulatory molecules - RNA interference. These RNA molecules are capable of very efficient gene silencing. The main pathways of this mechanism are used by two major types of small noncoding RNAs - microRNA (miRNA) and small interfering RNA (siRNA). These RNAs are a direct product of genes and are able to bind to mRNA molecules and influence their activity. Due to this knowledge, scientists started examining the effect of RNAi in cancer cells and tried to find a way how RNAi can be applied in therapy. The main topic of this thesis is the potential of miRNA replacement to harm cancer cell proliferation. In cancer cells, miRNA levels are downregulated or upregulated, depending on the nature of cancer and miRNA. Restoring levels of miRNAs can lead to elimination of cancer cell by apoptosis or stop cell in cell cycle arrest. miRNA replacement was used first to examine the function of a single miRNA in HeLa cancer cells. The change in the expression level of miRNA treated cells was verified by reverse transcriptase quantitative PCR and the proliferation inhibition was examined using proliferation assays. The most potent miRNAs inducing significant proliferation inhibition were examined. In the...
|
|
|
Selected aspects of methotrexate treatment in patients with rheumatoid arthritis
Hloch, Karel ; Pávek, Petr (advisor) ; Souček, Miroslav (referee) ; Tomčík, Michal (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Social and Clinical Pharmacy Doctoral Degree Program Clinical and Social Pharmacy Candidate MSc. Karel Hloch Supervisor prof. PharmD. Petr Pávek, Ph.D. Advisor assoc. prof. MUDr. Tomáš Soukup, Ph.D.; PharmD. Martin Doseděl, Ph.D. Title of Doctoral Thesis: Selected aspects of methotrexate treatment in patients with rheumatoid arthritis Introduction and objectives Rheumatoid arthritis (RA) is an autoimmune disease typically connected with chronic inflammation of the joints, causing their swelling and pain. The prevalence of RA is about 1% in the general population. A crucial role in higher morbidity and mortality in RA patients has been associated with increased inflammatory activity. Methotrexate (MTX), a drug with immunosuppressive activity, is the most frequent drug of choice used in RA therapy. It seems that main anti-inflammatory effect is mediated via release of purine nucleoside adenosine. The status of patients with inflammatory diseases is influenced by activation of A2a and A3 adenosine receptors. High caffeine (adenosine receptor antagonist) consumption may therefore lead to alteration of MTX treatment efficacy. 1) The aim of first study was to determine whether RA patients who had discontinued...
|
|
|
Influence of SERCA inhibitors on NO production and secretion of cytokines in macrofages
Vandasová, Eva ; Pávek, Petr (advisor) ; Jílek, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Eva Vandasová Supervisor: Doc. RNDr. Eva Kmoníčková, CSc., Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: The influence of SERCA inhibitors on production of nitric oxide and secretion of cytokines in macrophages Sesquiterpene lactones of plant origin such as thapsigargin (TG) and trilobolide (TB) are potent inhibitors of sarco/endoplasmic Ca2+ -ATPase (SERCA), enhancing thus concentration of intracellular calcium. TG has been found to exhibit prospective immunotherapeutic properties. It inhibits growth of slowly proliferating and non- proliferating cells, and inhibits replication of viruses. The aim of present work was to investigate immunomodulatory potential of these compounds and compounds chemically different from sesquiterpene lactone TG, i.e. clotrimazole, artemisinin, dihydroartemisinin, curcumin. All these drugs are related to SERCA inhibition. The effects were analyzed in cultures of rat and mouse resident peritoneal cells. Production of nitric oxide (NO) by animal macrophages was assayed using the Griess reagent after 24hour's culture. Supernatant levels of cytokines were determined by ELISA after 5-24hour's of culture. The rat peritoneal macrophages produced...
|
|
|
Effects of statins on Ras/Raf/ERK signaling in A431 cell line
Smutný, Tomáš ; Pávek, Petr (advisor) ; Trejtnar, František (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxikology Candidate: Tomáš Smutný Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Effects of statins on Ras/Raf/ERK signaling in A431 cell line The ERK pathway is the signal transduction cascade, which plays an important role in different cellular functions e.g. cellular proliferation, differentiation, and survival. Its inappropriate activation is often presented in human cancers. The pathway consists of the many proteins, but the interest concentrates especially on members of the Ras subfamily (particularly H-Ras or K-Ras). Ras proteins are GTPases, which are significantly included in the oncogenesis of many human cancers. The key role in the Ras proteins function represents their posttranslation modifications with the lipid. The covalent binding of prenyl moiety to Ras protein facilitates its attachment to the plasmatic membrane, which allows its function. The prenyl groups are formed during the synthesis of the cholesterol as its precursors. The inhibition of the prenylation results in Ras proteins inactivation of the ERK signal transduction cascade and suppression of uncontrolled cell division where the activating mutations of Ras proteins are presented. Statins hypolipidemic...
|
|
|
Molecular approaches in the analysis of chronic pain in mice
Kopecká, Dagmar ; Šimůnek, Tomáš (advisor) ; Pávek, Petr (referee)
Functional and structural plasticity of central synapses in pain pathways is responsible for the allodynia, hyperalgesia and pain memory caused by different insults like inflammation, neuropathy or trauma. Unfortunately molecular mechanism underlying plasticity at different levels of pain transmission are not yet clearly understood. mTOR is serine-threonine kinase playing a significant role in Long Term Potentiation (LTP) and in local protein translation in Hippocampus and Rac1 (Rho- GTPase) is the key regulator of actin cytoskeleton. Therefore we addressed the potential role of mTOR and Rac1 in activity-dependent plasticity in the spinal cord in the context of chronic pain. Using the western blot analysis, we examined the temporal expression of these proteins in L4+L5 spinal segments using inflammatory pain model. In case of Rac1 we found that the expression is unchanged. In case of mTOR we showed that the change in the expression is not significant but there is a clear trend of increase. To confirm these findings more expesiments are needed to be added. If this is confirmed there is a potential role of mTOR in pain processing.
|
|
|
Effect of Nicotinic Acid on infiltration of macrophages in the ischemic brain
Pokorná, Barbora ; Pávek, Petr (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Pharmacology and Toxicology Candidate: Barbora Pokorna Supervisor: Doc. PharmDr. Petr Pavek Ph.D. Specialized supervisor: Prof. Dr. med. Markus Schwaninger Title of diploma thesis: Effect of Nicotinic Acid on infiltration of macrophages in the ischemic brain Stroke is one of the leading causes of death worldwide and its effective protective treatment is still missing. Nicotinic acid has been a widely used substance to modify lipid profiles for many years and it successfully prevents clinical cardiovascular diseases. Recently explored receptor, GPR109A, causes its effect and it was found to be expressed in spleen, adipose, and immune cells including macrophages. The aim of this work is to investigate the effect of nicotinic acid on the infarct size during cerebral ischemia and to determine the role of macrophages in its effect. We compared two groups in our experiments, transgenic CD11bDTR mice and control wild type (WT) mice. Both groups were treated with diphtheria toxin (DT), then a middle cerebral artery occlusion was performed and afterwards mice were treated with either nicotinic acid or vehicle. We have found depletion of macrophages in CD11bDTR group induced by DT treatment and depletion of macrophages in WT...
|
|
|
Regulation of Human Carbonyl Reductase 3 (CBR3) Expression
Malátková, Petra ; Wsól, Vladimír (advisor) ; Pávek, Petr (referee) ; Machala, Miroslav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Petra Malátková Supervisor Prof. Ing. Vladimír Wsól, Ph.D. Title of Doctoral Thesis Regulation of Human Carbonyl Reductase 3 (CBR3) Expression The regulation of human carbonyl reductase 3 (CBR3) expression has been complete mystery until recently and is still not well understood. Because the transcriptional regulation of a gene is closely related to the function of encoded protein, the elucidation of the regulation of CBR3 might help to understand its physiological role which has not been elucidated up to the present. The promoter of CBR3 has been described in 2009. The CBR3 promoter contains several putative binding sites for various transcription factors. In 2010, we have shown that CBR3 is regulated via the Nrf2/ARE signaling pathway. This was the first study about the transcriptional regulation of CBR3. The involvement of Nrf2 in the regulation of CBR3 has been recently confirmed by another research group. The functional antioxidant response element (ARE) is located at 2698 bp upstream of the translation initiation codon of CBR3 (−2698ARE). However, the analysis of CBR3 promoter encompassing 2500 bp indicated the presence of cis regulatory upstream element in sequence between...
|
|
|
Vliv O-glykosylace v onkofetálním fibronektinu na kostní formaci
Lejsalová, Alžběta ; Šimůnek, Tomáš (advisor) ; Pávek, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Performed at Institute of Immunology The Ruprecht-Karls-University Heidelberg Candidate: Alžběta Lejsalová Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Specialized supervisor: Prof. Dr. Inaam Nakchbandi Title of diploma thesis: The Influence of the O-glycosylation in oncofetal fibronectin on the bone formation Hepatic osteodystrophy is a major complication in patients with chronic cholestatic liver diseases which significantly contributes to decreased quality of life. It was established that increased levels of the oncofetal domain of fibronectin correlated with bone loss and decrease in bone formation in patients with primary biliary cirrhosis. The oncofetal fibronectin is characterized by the O-glycosylation in the variable domain. Another O-glycosylation is found on the NH2-terminus. The aim of this project was to prepared O-deglycosylated fibronectin isoforms and fibronectin knockdown mammalian cells for further research on the effect of O-glycosylation on the bone formation.
|
|
|
The role of microRNA in physiology and pathology
Janáková, Barbora ; Matoušková, Petra (advisor) ; Pávek, Petr (referee) ; Dostálová Merkerová, Michaela (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Barbora Hanousková Supervisor: doc. Ing. Petra Matoušková, Ph.D. Title of Doctoral Thesis: The role of microRNA in physiology and pathology MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that play an important role in the regulation of gene expression. They are evolutionarily highly conserved and are present in the genome of all eukaryotic organisms, suggesting their importance in physiological processes. Due to the tissue specificity and their involvement in the pathogenesis of various diseases, miRNAs have been widely studied in connection with their potential use as specific and early biomarkers, or as a therapeutic target. The doctoral thesis, written in the form of an annotated set of publications, dealt with the study of miRNAs in various systems in vitro and in vivo, focusing on their role in adipogenesis and their use as biomarkers of pathological conditions. The introduction summarizes the theoretical information on epigenetic regulation with a more detailed focus on miRNAs, followed by comments on the author's individual publications and brief conclusions. In two studies using mouse models, several miRNAs were identified to have their expression profile...
|
guest ::
