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Comparison of Roma and non-Roma injecting drug users using HCV screening and treatment at the addictology clinic in Brno
Věchet, David ; Gabrhelík, Roman (advisor) ; Lukavská, Kateřina (referee)
INTRODUCTION: Current research directed to socially excluded localities shows the correctness of the concept of targeted research and medical care directly in socially excluded localities with risky behavior. The high prevalence not only of infectious diseases directly related to the use of addictive substances, but also of other infectious diseases such as lues, testifies to the long-term absence of systematic medical and preventive care. OBJECTIVES: To compare medical anamnestic data, risk behavior rates and drug career progression in a cohort of Roma and non-Roma drug users visiting an addiction clinic located in a socially excluded location. To determine whether there are significant differences in family health burden, hospitalizations, surgeries, allergies, current medication use, current specialist visits, and access to health care among the cohorts mentioned, and whether there are differences in risky behavior and drug career progression among these cohorts . RESEARCH SAMPLE: The research set includes a total of 232 injecting drug users. 120 persons from this group are Roma injection users and 112 persons from this group are non- Roma injection users. METHODS: Using statistical-analytical methods and observing ethical rules, data from four types of questionnaires, which NGHS Remedis uses...
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Selected genetic factors modifying the natural course of viral infections in organ transplant settings
Chmelová, Klára ; Šperl, Jan (advisor) ; Husa, Petr (referee) ; Brůha, Radan (referee)
Solid organ transplantation (SOT) represents a life-saving procedure and a future perspective for patients suffering from organ failure. On the other hand, SOT recipients are burdened with numerous complications, including infections or lifelong administration of immunosuppressive medication. There are several well-known factors related to graft and patient survival, including general health status, age at the time of SOT, diagnosis leading to SOT, acute or antibody-mediated rejection, development of the metabolic syndrome and complications including viral diseases. Viral infections in SOT recipients may present with a very distinct natural history compared with the healthy population. Several can cause immune activation leading to graft rejection; others can be associated more likely with immune tolerance. We aimed to identify the impact of variants of selected genes on the natural history of various viral diseases in SOT recipients and thus their overall outcome, morbidity and graft survival. Cytomegalovirus (CMV) infection is the most common viral infection in SOT recipients. We focused on the role of the IL28B rs12979860 locus genotype in the risk of CMV disease occurrence. We proved the T allele is associated with a more frequent occurrence of CMV disease in liver transplant (LTx) recipients...
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Effect of ADAR1 enzyme on hepatitis C virus life cycle
Kubů, Martin ; Vopálenský, Václav (advisor) ; Fraiberk, Martin (referee)
Hepatitis C virus (HCV) is a virus of the family Flaviviridae whose genome consists of ,,+RNA" molecule. It causes the disease hepatitis Cepatitida typu C, which affects tens of millions of people worldwide. Although there is an effective treatment for this type of hepatitis, a preventive vaccine against the HCV virus has not yet been developed. Several ambigious works focused on the relationship between HCV and the enzyme adenosine deaminase acting on double-stranded RNA 1 (ADAR1) were published in the past. This dimeric double-stranded RNA binding enzyme is a part of innate immunity and causes catalytic conversion of adenosine to inosine, which is recognized by cellular mechanisms as guanine, which ultimately leads to mutations in the affected dsRNA molecule. The works published so far attribute an antiviral function to the ADAR1 enzyme in the context of HCV infection. However, vectors containing the entire HCV genome were not used in these works, and a cell line with deletion od the ADAR1 gene has never been used so far. The actual relationship between the ADAR1 enzyme and the HCV virus has not yet been reliably verified. The aim of this thesis was to gain a deeper understanding of the relationship between the HCV virus and the ADAR1 enzyme. For this task, HCV permissive Huh7.5 cell lines with...
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Novel hepatitis C virus proteins
Zeman, Jakub ; Vopálenský, Václav (advisor) ; Horníková, Lenka (referee)
The hepatitis C virus (HCV) is a major etiological agent of chronic liver diseases. More than 170 million people worldwide are chronically infected, and more than 100 thousand of them develop hepatocellular carcinoma a year. HCV is an enveloped, positive-sense single-stranded RNA virus (+ssRNA virus) of the family Flaviviridae. Its genome is translated to produce a single polyprotein precursor that is further processed by cellular and viral proteases to form 10 viral proteins. Moreover, there is another protein encoded in an alternative reading frame. Two alternative translation mechanisms have been proposed for expression of this alternative reading frame protein (ARFP): a frameshift mechanism and translation initiating from internal start codons. Despite ten years of research its role in vivo is not yet explained. It appears that secondary structures in the core encoding region of HCV genome but not ARFP expression are required for robust viral translation and replication. The results of recent studies suggest that mutations distorting these structures may result not only in slowing down the viral cycle but also in a brand new and utterly unusual serological profile in patients as well as an increased level of expression of ARFP.
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Viral hepatitis: novel insights and novel therapeutic interventions.
Davidovová, Eva ; Pávek, Petr (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Bc. Eva Davidovová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Viral hepatitis: novel insights and novel therapeutic interventions. Viral hepatitis is a well-known worldwide problem. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are characterized by the development of serious complications, especially with regard to the transition to the chronic stage of the disease, associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Interactions between viruses and host cells are quite complicated and not always fully understood. In general, the infection cycle of viruses is a multi-step process. A closer understanding of the entire life cycle of the virus is a major prerequisite for the invention of effective drugs. Viral hepatitis B and C have long been treated mainly with interferon alfa. Ribavirin was later added to HCV treatment and nucleoside / nucleotide analogs (NA) were introduced for HBV. Interferon was later pegylated to improve its properties. However, these drugs did not provide sufficient efficacy and were additionally associated with a number of side effects. It is precisely because of these disadvantages of the current...
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Optimizing of the regime of marker's examination of clinically important infections in blood donors
Dušková, Daniela ; Tesař, Vladimír (advisor) ; Borovanský, Jan (referee) ; Průša, Richard (referee)
Project title: Optimalization of the regime of marker's examination of clinically important infections in blood donors Project author: Daniela Dušková, M.D. Project supervisor: prof. Vladimír Tesař, M.D., Dr.Sc., MBA, FASN The aim of this project is to contribute to the discussion about introducing the methods of molecular biology into the routine blood donor testing in the transfusions departments in the Czech Republic. The theoretical part includes a brief history and some turning points in transfusion medicine. The next part within the theoretical section is dedicated to the problems of infectious diseases concerning transfusion and the general examination processes used during the selection of blood donors. The end of the theoretical part concentrates on existing possibilities of markers' examination of clinically important infections in blood donors, including the list of processes performed in the Czech Republic, the European Union and other countries. The practical part describes this study, ie. the routine screening test of blood donors using the CMIA method (a routine method) and using RT-Real Time PCR method (a molecular biology method) for detecting infectious markers (HCV, HBV, HIV). Within this part, the principle of both methods and the process of actual examinations are described in...
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Role of RNA helicases in antiviral defense
Krbušek, David ; Vopálenský, Václav (advisor) ; Janovec, Václav (referee)
Hepatitis C virus is an important human pathogen against which there is no immunization yet. This virus is detected by the immune system of the eukaryotic host cell by pattern recognition receptors of the RLR receptor family, which is part of the innate immune system. These RLR receptors detect the presence of hepatitis C virus and initiate a signaling cascade triggering an antiviral immune response. In this thesis, the role of cytoplasmic PRRs involved in antiviral defense during hepatitis C virus infection of eukaryotic cells has been described and determined. Key words Helicase, RIG-I, MDA5, pattern-recognition receptors, HCV, virus
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A study of the HCV IRES variability: An experimental approach coupled with design of a large-scale mutation database
Khawaja, Anas Ahmad ; Pospíšek, Martin (advisor) ; Hirsch, Ivan (referee) ; Valášek, Leoš (referee)
Translation initiation in the hepatitis C virus (HCV) occurs through a cap- independent mechanism that involves an internal ribosome entry site (IRES) capable of interaction with and utilization of the eukaryotic translational machinery. We focused on the structural configuration of the different HCV-IRES domains and the impact of IRES primary sequence variations on secondary structure conservation and function. For this purpose we introduced into our laboratory, methods such as denaturing gradient and temperature gradient gel electrophoresis for screening the degree of heterogeneity and total amount of HCV-IRES variability accumulated in HCV infected patients over a period of time. The selected samples showed variable migration pattern of the HCV-IRES (from all the patients) visualized in DGGE and TGGE, were sequenced and evaluated for translation efficiency using flow cytometry. In some cases, we discovered that multiple mutations, even those scattered across different domains of HCV-IRES, led to restoration of the HCV-IRES translational activity, although the individual occurrences of these mutations were found to be deleterious. We propose that such observation may be attributed to probable long- range inter- and/or intra-domain functional interactions. We established a large-scale HCV-IRES...
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Elucidation of ERK1 and ERK2 protein kinases effect on cap-independent translation initiation
Přibyl, Miroslav ; Vopálenský, Václav (advisor) ; Vomastek, Tomáš (referee)
Protein kinases ERK1 and ERK2 are one of the most studied proteins in cell signalling. Both proteins are involved in a plethora of processes, such as phosphorylation and activation of kinases as part of signalling pathways. Enzymes ERK1 and ERK2 are part of MAPK/ERK signalling cascade, connected to many cellular including cell proliferation, cell growth or differentiation. The MAPK/ERK signalling cascade is often activated in different types of tumors, making it a candidate for developing new chemical inhibitors. One of the important questions in fundamental research of ERK1 and ERK2 protein kinases is the search for difference between these proteins. Current knowledge points to redundancy of both proteins, howver several examples suggest otherwise. Recently, the work presented in Casanova et al. 2012 indirectly suggests divergent effect of ERK1 and ERK2 on cap-independent translation initiation. In the Laboratory of RNA biochemistry we focus on HCV IRES (Hepatitis C Virus Internal Ribosome Entry Site) dependent translation initiation. This diploma thesis lead to establish RNA interference method in our laboratory and to establish reporter system to study ERK1 and ERK2 effect on HCV IRES dependent translation initiation. Based on our data acquired during our research, we present in this work...
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Optimizing of the regime of marker's examination of clinically important infections in blood donors
Dušková, Daniela ; Tesař, Vladimír (advisor) ; Borovanský, Jan (referee) ; Průša, Richard (referee)
Project title: Optimalization of the regime of marker's examination of clinically important infections in blood donors Project author: Daniela Dušková, M.D. Project supervisor: prof. Vladimír Tesař, M.D., Dr.Sc., MBA, FASN The aim of this project is to contribute to the discussion about introducing the methods of molecular biology into the routine blood donor testing in the transfusions departments in the Czech Republic. The theoretical part includes a brief history and some turning points in transfusion medicine. The next part within the theoretical section is dedicated to the problems of infectious diseases concerning transfusion and the general examination processes used during the selection of blood donors. The end of the theoretical part concentrates on existing possibilities of markers' examination of clinically important infections in blood donors, including the list of processes performed in the Czech Republic, the European Union and other countries. The practical part describes this study, ie. the routine screening test of blood donors using the CMIA method (a routine method) and using RT-Real Time PCR method (a molecular biology method) for detecting infectious markers (HCV, HBV, HIV). Within this part, the principle of both methods and the process of actual examinations are described in...
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