|
|
Laboratory markers in acute heart attack
Dvořáková, Kristýna ; Skálová, Lenka (advisor) ; Dršata, Jaroslav (referee)
Charles university, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Study program: Healthcare bioanalytics Candidate: Kristýna Dvořáková Thesis supervizor: prof. RNDr. Lenka Skálová, Ph.D. Consultant: Mgr. Martina Hrdinová Title of bachelor thesis: Laboratory markers in the diagnosis of acute myocardial infarction The basic laboratory examination in the diagnosis of acute myocardial infarction (AIM) is primarily the determination of cardiac troponins. The object of this work was to create an overview of markers used in the diagnosis of AIM and to determine cardiac troponins T and I by highly sensitive methods on two different automatic analyzers cobas e 801 and Alinity i in the laboratory of clinical biochemistry. We used diagnostic kits from two different manufacturers to analyze troponins. Cardiac troponins T and I are determined by highly sensitive chemiluminescence methods, which make it possible to capture the increase in concentrations at an early stage of myocardial disability. I compared and evaluated the measured values of troponins in samples from a selected group of patients, in which men aged between 51-70 years predominated. This group is most at risk in the diagnosis of AIM. I made graphical and statistical processing of results separately for men and women....
|
|
|
Degradation of hyaluronic acid in the skin and percutaneous absorption of exogenous hyaluronic acid through the skin
Exnerová, Andrea ; Skálová, Lenka (advisor) ; Szotáková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Andrea Exnerová Supervisor: Mgr. Petra Žádníková, Ph.D. prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Degradation of hyaluronic acid in the skin and percutaneous absorption of exogenous hyaluronic acid through the skin Up to half of the body's total hyaluronic acid (HA) content is present in the skin. HA acts as an organizer of the extracellular matrix and is involved in maintaining skin hydration and elasticity. In the last decade, several important findings have been added to the field of HA degradation in the skin, and one of the aims of this thesis was to create a comprehensive overview. Degradation of HA in the dermis was elucidated by the discovery of the essential role in the degradation of HA in dermal fibroblasts played by the KIAA1199 protein. In the epidermis, the lysosomal enzyme hyaluronidase 1 is overexpressed in the stratum granulosum just below the stratum corneum (SC). It is uncertain how HA is internalized into the keratinocytes or whether only intracellular HA is degraded in this way. Epidermal degradation of HA remains elusive. HA is part of a range of topically applied products on the skin, mainly due to its unique moisturizing properties, but it is not yet...
|
|
|
Changes in expression of biotransformation enzymes in nematodes affected by albendazole
Štěrbová, Karolína ; Skálová, Lenka (advisor) ; Trejtnar, František (referee)
5 ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Karolína Štěrbová Supervisor: prof. RNDr. Lenka Skálová Ph.D. Title of diploma thesis: Changes in expression of biotransformation enzymes in nematodes affected by albendazole Barber's pole worm (Haemonchus contortus) is highly pathogenic parasitic nematode, which assaults gastrointestinal system of small ruminants. Disease. Which caused is named by the agent haemonchoses. Long-term infection leads to develop of anaemia, lose weight of host and often even death. For treatment of this disease, synthetic antiparasitic drugs called anthelmintics are used. However, worldwide problem is growth of resistance against all used anthelmintics. Cause of this problem is probably common and unreasonable using of anthelmintics and the exposure of the parasites to sub-lethal doses. This thesis is focused on study of the mechanisms of resistance of barber's pole worm to albendazole, anthelmintic belonging to benzimidazoles group. The increased expression of biotransformation enzymes could contribute to resistance development. In our study, the influence of albendazole on expression of selected genes in adults of H. contortus from the ISE (Inbread Susceptible Edinburgh) strain was studied. Worms...
|
|
|
Metabolism of flubendazole in human liver subcellular fractions
Holubová, Jana ; Skálová, Lenka (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Jana Holubová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Metabolism of flubendazole in human liver subcellular fractions Flubendazole (FLU), a benzimidazole anthelmintic drug with a broad spectrum of activity and low toxicity has been used in veterinary as well as human medicine for a long time. Owing its mechanism of action, based on the specific binding to tubulin, FLU is now considered a promising anti-cancer agent. However, we do not have enough information about its biotransformation in human. In our project, subcellular fractions from the liver of 12 human patients (6 males and 6 females) were used to study the stereospecificity, cellular localization, coenzyme preference and possible inter-individual or sex differences in FLU reduction. In addition, the risk of FLU interaction with other drugs was evaluated. Results showed that FLU is predominantly reduced in cytosol and the NADPH coenzyme is preferred. The strict stereospecificity of FLU carbonyl reduction was proven and carbonyl reductase 1 was identified as the main enzyme of FLU reduction in the human liver. A higher reduction of FLU and a higher level of carbonyl reductase 1 protein was found in males than in...
|
|
|
The changes in expression of selected drug-metabolizing enzymes in parasites after exposition to sublethal doses of drugs
Pasák, Michael ; Skálová, Lenka (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Michael Pasák Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The changes in expression of selected drug-metabolizing enzymes in parasites after exposition to sublethal doses of drugs The parasite, which causes significant losses of small ruminants through a disease called haemonchosis, is the abomasal nematode Haemonchus contortus. IVM is one of the anthelmintics used in veterinary medicine to eliminate haemonchosis. The main problem with this parasite is the presence of drug resistance to almost all administered anthelmintics including IVM. It is believed that xenobiotic-metabolizing enzymes such as cytochromes P450 (CYPs) and membrane efflux transporters P- glycoproteins (P-gps), play the role in resistance in H. contortus. This study focuses on the effect of sublethal doses of IVM on expression of selected CYPs and P-gps. Females and males of susceptible ISE strain H. contortus were separated before our experiment. After incubation of nematodes with three different concentrations of IVM, RNA was isolated and the changes in expression of selected genes were analyzed using qPCR. Significant sex-differences were observed in inducibility of tested genes. Significant...
|
|
|
Study of expression of glutathione peroxidases in mice with induced obesity
Zemanová, Kateřina ; Matoušková, Petra (advisor) ; Skálová, Lenka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Zemanová Supervisor: Ing. Petra Matoušková, PhD. Title of thesis: Study of expression of glutathione peroxidases in mice with induced obesity Obesity is serious worldwide health issue. The most common reason for developing obesity is unbalanced intake and energy expenditure. It is connected to a higher amount of reactive oxygen species (ROS) in organism, which increases the risk of developing health issues related to obesity. Between these issues are belonging mainly cardiovascular diseases, metabolic syndrome or type two diabetes mellitus. The goals of many studies focusing on obesity are identification of new biomarkers, searching for target structures for obesity treatment and potentially developing antiobesity drugs. Glutathione peroxidases (GPxs) are enzymes with antioxidation activity. Currently, there are eight GPxs described. They can reduce the amount of reactive oxygen species (ROS) produced in our body. The GPxs can cause damage to the surrounding tissues in case of their accumulation and they are related to many diseases. Based on these findings, efforts have been made to discover how the expression of GPxs genes is regulated and how they are connected to microRNA...
|
|
|
The changes in expression of selected drug-metabolizing enzymes in parasites after exposition to sublethal doses of drugs
Pasák, Michael ; Skálová, Lenka (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Michael Pasák Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The changes in expression of selected drug-metabolizing enzymes in parasites after exposition to sublethal doses of drugs The parasite, which causes significant losses of small ruminants through a disease called haemonchosis, is the abomasal nematode Haemonchus contortus. IVM is one of the anthelmintics used in veterinary medicine to eliminate haemonchosis. The main problem with this parasite is the presence of drug resistance to almost all administered anthelmintics including IVM. It is believed that xenobiotic-metabolizing enzymes such as cytochromes P450 (CYPs) and membrane efflux transporters P- glycoproteins (P-gps), play the role in resistance in H. contortus. This study focuses on the effect of sublethal doses of IVM on expression of selected CYPs and P-gps. Females and males of susceptible ISE strain H. contortus were separated before our experiment. After incubation of nematodes with three different concentrations of IVM, RNA was isolated and the changes in expression of selected genes were analyzed using qPCR. Significant sex-differences were observed in inducibility of tested genes. Significant...
|
|
|
Study of activation properties of insulin, IGF-1 and IGF-2 analogs towards the receptors for insulin and IGF-1
Chrudinová, Martina ; Selicharová, Irena (advisor) ; Šulc, Miroslav (referee) ; Skálová, Lenka (referee)
The insulin/insulin-like growth factor signaling axis is a complex system that is involved in the regulation of metabolism and body growth. It includes three related peptide hormones: insulin and two insulin-like growth factors (IGF-1 and IGF-2), and their receptors: two isoforms of insulin receptor (IR-A and IR-B), and IGF-1 receptor (IGF-1R). Whereas insulin is involved predominantly in regulation of the metabolism, IGFs participate mainly in the regulation of cell growth, proliferation and differentiation. Due to the similarities in the structures of both the hormones and the receptors, all the hormones can bind and activate all the receptors, although with different potencies. At which point and how are the "metabolic" and "mitogenic" functional outcomes of the system diversified, as well as the structural determinants responsible for the different affinities of the hormones to the individual receptors, is still not completely understood. Deregulation of the insulin/IGF system can result in many types of pathological states, mainly diabetes mellitus and cancer. Therefore, to deeply understand the functioning of the insulin/IGF system to the structural details is crucial for development of analogs with desirable properties, that are of great clinical interest. First of all, we developed a...
|
|
|
Metabolism of flubendazole in human liver subcellular fractions
Holubová, Jana ; Skálová, Lenka (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Jana Holubová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Metabolism of flubendazole in human liver subcellular fractions Flubendazole (FLU), a benzimidazole anthelmintic drug with a broad spectrum of activity and low toxicity has been used in veterinary as well as human medicine for a long time. Owing its mechanism of action, based on the specific binding to tubulin, FLU is now considered a promising anti-cancer agent. However, we do not have enough information about its biotransformation in human. In our project, subcellular fractions from the liver of 12 human patients (6 males and 6 females) were used to study the stereospecificity, cellular localization, coenzyme preference and possible inter-individual or sex differences in FLU reduction. In addition, the risk of FLU interaction with other drugs was evaluated. Results showed that FLU is predominantly reduced in cytosol and the NADPH coenzyme is preferred. The strict stereospecificity of FLU carbonyl reduction was proven and carbonyl reductase 1 was identified as the main enzyme of FLU reduction in the human liver. A higher reduction of FLU and a higher level of carbonyl reductase 1 protein was found in males than in...
|
|
|
Modulatory effects of blueberry extract on the activities and expression of selected biotransformation enzymes in rat
Láníčková, Tereza ; Skálová, Lenka (advisor) ; Boušová, Iva (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biochemical Sciences Candidate: Tereza Láníčková Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Modulatory effects of bilberry extract on the activities and expression of selected biotransformation enzymes in rat Bilberry (Vaccinium myrtillus L., Ericacea) is one of the richest sources of anthocyanins. These bioactive polyphenolic secondary metabolites give bilberry not only a characteristic blue/black colour, but they are also responsible for many health benefits. Therefore, bilberry has potential use in the treatment and prevention of conditions associated with visual disorders, inflammation, dyslipidemia, hyperglycemia or in some other disorders associated with increased oxidative stress. The aim of this study was to evaluate the effect of bilberry extract, which was administrated for 29 and 58 days, on activity and expression of selected biotransformation enzymes in rat liver. Enzymatic activity and expression of mRNA was determined in the cytosols and microsomes of liver tissue from control and influenced rats. In this study, spectrophotometric or HPLC method was used to measure the activities of aldehyde reductase (AKR1A1), hydroxysteroid dehydrogenase (AKR1C), glutathione-S-transferase (GST),...
|
guest ::
RSS feed.