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Analysis of vaccine utilization and spontaneous adverse events reports in influenza vaccine
Podskalská, Markéta ; Zimčíková, Eva (advisor) ; Kolmanová, Eliška (referee)
Analysis of vaccine utilization and spontaneous adverse events reports in influenza vaccine Author: Markéta Podskalská Supervisor: PharmDr. Eva Zimčíková, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction and goal: Influenza is a contagious disease of the respiratory system. It is caused by influenza viruses and appears in annual outbreaks. The best form of influenza prevention is vaccination against influenza viruses on yearly basis. The vaccination has many benefits, but some side effects may appear as well. Goal of this thesis was to analyse and evaluate reports of side effects of influenza vaccination between years 2004-2017 and to evaluate the use of influenza vaccines from 2004 to 2022. Methodology: The Central Database of Adverse Events Reporting of the State Institute for Drug Control was used as the data source. Reports with the ATC code J07BB in the period from 2004 to 2017 were evaluated. Information about the patient, reporting person, the region where the notification was filed, the method of reporting and details concerning adverse events were analysed. These details included the number and severity of adverse effects, their predictability and final outcome. Data on influenza vaccine usage were provided by SÚKL....
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Health literacy of visitors to a selected pharmacy in the field of infectious respiratory diseases
Kubíková, Daniela ; Hanušová, Jaroslava (advisor) ; Syřiště, Ivo (referee)
The content of the diploma thesis is the topic of infectious respiratory diseases with a focus on the knowledge of visitors to the selected pharmacy in this area. The theoretical part of the diploma was focused on gathering the necessary knowledge that was related to the researched issues using the literature and electronic resources. The theoretical part of the thesis provides a brief description of health literacy, infection and selected terminology, anatomy of the human respiratory system, there are also described manifestations of selected infectious respiratory diseases, their clinical picture, disease course, treatment options, vaccination and prevention. In the practical part, the results of the research survey, evaluation of predetermined goals, comparison of the findings and recommendations for practice based on the findings are recorded. The introduction of the practical part describes the place where the investigation took place using the method of individual interviews with visitors to the selected pharmacy. The aim of the diploma thesis was to evaluate the health literacy of visitors to a selected pharmacy in the field of infectious respiratory diseases. The results of our own survey show that visitors to the selected pharmacy are health literate in the field of infectious respiratory...
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Influence of sigle nucleotide mutations on influenza pathogenicity
Nitkulincová, Lucie ; Drda Morávková, Alena (advisor) ; Král, Jiří (referee)
Influenza virus caused several times the global concerns about the emergence of pandemics, in recent years. The most serious problem, in the fight against this virus, is its ability to quickly change its unusually antigenic specificity by reassortment and point mutations, especially in surface glycoproteins - haemagglutinin and neuraminidase. In this thesis I focused on point mutations in the hemagglutinin of influenza virus causing change in binding preference, which enables both influenza virus transmission between different hosts and unlimited proliferation in their tissues. The permanent change in amino acid sequence and thus the surface of hemagglutinin also largely prevents the host's immune system to destroy the virus efficiently and quickly enough to recognize when another infection. Each of the haemagglutinin subtypes has a different amino acid positions affecting its binding preference. Their summary is included in this thesis. Key words: influenza, single nucleotide mutations, pandemia, patoghenicity, hemagglutinin
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Inovation in influenza vaccines
Satoriová, Martina ; Drda Morávková, Alena (advisor) ; Motlová, Lucia (referee)
Influenza viruses annually infect 3 to 5 millions of people worldwide, cause annually many hospitalizations, 250 000-500 000 deaths and significant economical losses. The vaccines still remain the most efficient way of prevention of this infectious disease. Conventional egg- based vaccines are used for more than 60 years. Although they are safe, they have many disadvantages. Their main disadvantage is the relatively low effectiveness and time-limited induced immunity. The need for annually updates of their composition due to an antigenic variability of viral surface proteins can be considered a disadvantage as well. What is more, the dependence on an egg suply and a way too long time of preparation might be limiting in the case of pandemic. The development of an universal vaccine that would induce a broad imunne response against different strains of Influenza and longlasting protection is a worldwide priority.
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Synthesis of peptidic inhibitors targeting PA-PB1 interface of influenza RNA polymerase
Palacková, Miroslava ; Machara, Aleš (advisor) ; Veselý, Jan (referee)
The submitted Thesis deals with preparation of a hexapeptides inhibiting protein-protein interaction of PA-PB1 subunits of influenza RNA polymerase. Crucial part of the Thesis represent modifications of particular small hexapeptide at its two "hot spots". It means at positions that significantly contribute to the binding of both subunits. These modifications resulted in preparation of two series of distinct hexapeptides. With regards to the fact that one designed hexapeptide contains unnatural and commercially unavailable amino acids this amino acid had to be prepared from simple building blocks. Apart from aforementioned work the Thesis also covers effort to prepared bicyclic peptide that contains sequences of peptidic inhibitor of protein-protein interactions and also cell-penetration peptide. Key words: synthesis, peptides, inhibitors, influenza, polymerase
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Infectious complications in chronic renal failure
Kielberger, Lukáš ; Eiselt, Jaromír (advisor) ; Dusilová Sulková, Sylvie (referee) ; Matoušovic, Karel (referee)
INFECTIOUS COMPLICATIONS IN CHRONIC RENAL FAILURE Infections represent a serious problem in chronic kidney disease (cohort and they are) associated with signifficant morbidity and mortality. The thesis originated in the nephrology division of the Department of Internal Medicine I., Charles University Teaching Hospital and Medical Faculty in Pilsen, an institution with a long standing research activity in the field. In the theoretical part of this work, a general summary of infectious complications in chronic kidney disease population is presented. The other part of this work presents results of our research dealing with pharmacoeconomical aspects of cytomegalovirus infection and finally our results in the field of influenza vaccination. The Aim of the first presented work was to evaluate the cost impact of four different strategies for prevention of cytomegalovirus infection after renal transplantation. We provide post hoc analysis of 2 randomized studies performed in our department and calculating direct CMV-related expenses using valacyclovir prophylaxis, ganciclovir prophylaxis, preemptive vlaganciclovir treatment and deferred therapy. To simulate ihe impact of varying prices of prharmacotherapy or diagnostic procedures, a sensitivity analysis was performed. With respect to our results, valacyclovir...
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Spatiotemporal analysis of spreading of influenza epidemic in Czechia
Švábová, Lea ; Netrdová, Pavlína (advisor) ; Šídlo, Luděk (referee)
Influenza is accompanying humans for centuries and for centuries people are dying in hundreds. Every year there is seasonal influenza epidemy, which is caused by common circling influenza viruses in which happened small changes. Every 10-20 years is discovered completely new influenza virus subtype which is created by big genetical changes. Most affected areas are poor states in Asia or in different countries with insufficient hygiene or unavailable medical care, these countries also have huge mortality. Czech Republic wasn't independent for many centuries and describing historical evolution of this disease is very complicated, but we have few data form Spanish influenza time. Influenza and other acute or chronical respiratory are reported, so it is possible to create some demographic or statistical analysis. Unfortunately, in Czech Republic only 50-55 % of all cases are reported. This work is devoted to spatiotemporal analysis of influenza in Czechia and is done through statistical analysis like corelation analysis or time series analysis that are examining spatiotemporal way of the spread of the virus. Goals of this thesis with the help of these methods are to answer questions about questions concerning the spatiotemporal patterns of influenza spread, therefore what the repeatability of...
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Acyclic nucleosides of 3-hydroxypyrazine-2-carboxamide bases
Chaloupecká, Ema ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This thesis deals with the preparation of acyclic nucleosides and nucleoside phosphonates of compounds T-705 (6-fluoro-3-hydroxypyrazine-2-carboxamide) and T-1105 (3-hydroxypyrazine-2-carboxamide). Acyclic nucleoside phosphonates are substances that can terminate viral RNA or DNA replication, and some of them are used in the treatment of viral diseases. T-705 and T-1105 have shown activity against the influenza virus, and T-705 has already been approved for its treatment in Japan. Since both compounds mimic natural nucleobases in the body, their acyclic nucleosides and nucleoside phosphonates also have the potential to be biologically active. Methods for the synthesis of 3-fluoro-2-(phosphonomethoxy)propyl and 3-hydroxy-2-(phosphonomethoxy)propyl derivatives of T-705 and T-1105, their prodrugs containing lipophilic groups for the improvement of the pharmacokinetic properties and also their phosphonate diphosphates, suitable for the biological activity measurements, have been proposed. Some of these derivatives were subsequently prepared. Key words: acyclic nucleosides, acyclic nucleoside phosphonates, T-705, T-1105, favipiravir, antiviral activity, influenza
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Synthesis of peptidic inhibitors targeting PA-PB1 interface of influenza RNA polymerase
Palacková, Miroslava ; Machara, Aleš (advisor) ; Veselý, Jan (referee)
The submitted Thesis deals with preparation of a hexapeptides inhibiting protein-protein interaction of PA-PB1 subunits of influenza RNA polymerase. Crucial part of the Thesis represent modifications of particular small hexapeptide at its two "hot spots". It means at positions that significantly contribute to the binding of both subunits. These modifications resulted in preparation of two series of distinct hexapeptides. With regards to the fact that one designed hexapeptide contains unnatural and commercially unavailable amino acids this amino acid had to be prepared from simple building blocks. Apart from aforementioned work the Thesis also covers effort to prepared bicyclic peptide that contains sequences of peptidic inhibitor of protein-protein interactions and also cell-penetration peptide. Key words: synthesis, peptides, inhibitors, influenza, polymerase
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Development of high-throughput screening assay for the identification of inhibitors targeting influenza A polymerase
Karlukova, Elena ; Konvalinka, Jan (advisor) ; Obšil, Tomáš (referee)
Influenza virus A circulates in birds and mammals and causes severe infectious disease that affects from 3 to 5 million people each year. There are two classes of anti-influenza drugs currently available: neuraminidase and M2 channel inhibitors. However, increasing resistance against these two types of inhibitors along with the potential emergence of new viral strains and unpredictability of pandemic outbreaks emphasize an unmet need for new types of inhibitors. RNA-dependent influenza polymerase serves as a novel promising target for the development of anti-influenza medications. The aim of this master thesis is to develop in vitro high-throughput assays for screening of compounds targeting influenza RNA polymerase, particularly, its cap binding and endonuclease domains. For cap-binding domain the screening is based on DIANA (DNA-linked Inhibitor ANtibody Assay) method that was recently developed in our laboratory; for endonuclease domain, the method is based on AlphaScreen technology. For the purposes of the methods development, recombinant cap binding domain of PB2 subunit and N-terminal endonuclease domain of PA subunit of influenza polymerase were expressed with appropriate fusion tags and purified using affinity and gel permeation chromatography. The probes for the screening assays were...
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