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Placental homeostasis of monoamines; effect of gestation age
Mahrla, Filip ; Štaud, František (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Filip Mahrla Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: PharmDr. Rona Karahoda, Ph.D. Title of diploma thesis: Placental homeostasis of monoamines; effect of gestation age Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence suggests their involvement in placental development and functions and a crucial role in fetal development and programming. Nonetheless, a comprehensive characterization of catecholamine synthesis, degradation, and transport in the fetoplacental unit is still lacking. Thus, in this thesis, we aimed to provide a comprehensive evaluation of catecholamine metabolism and transport in the fetoplacental unit. Gene and protein expression was evaluated using quantitative polymerase chain reaction (PCR) and Western blot analysis, respectively. Firstly, using several placental cell models (BeWo, JEG-3, primary trophoblast cells), we identified components of cellular catecholamine handling associated with the trophoblast cells. Next, we determined the effect of advancing gestation on the placental catecholamine system in humans (first trimester vs. term placenta) and...
Functional receptor alterations in urinary bladder and urethra in an animal model of chronic prostatitis-chronic pelvic pain syndrome
Rataj, Jan ; Štaud, František (advisor) ; Vokřál, Ivan (referee)
University of Gothenburg; Charles University Sahlgrenska Academy; Faculty of Pharmacy in Hradec Králové Institute of Neuroscience and Physiology; Department of Pharmacology & Toxicology Student: Jan Rataj Supervisor: Michael Winder, Ph.D.; Özgü Aydogdu, M.D.; Prof. PharmDr. František Štaud, Ph.D. Title of diploma thesis: Functional receptor alterations in urinary bladder and urethra in an animal model of chronic prostatitis-chronic pelvic pain syndrome Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological disorder. Current available pharmacological treatment options are not effective enough, mostly due to the etiology of CP/CPPS not being fully understood. My thesis aimed to examine potential urethral changes, using immunohistochemistry methods and an organ bath setup, in a rat model of CP/CPPS. The thesis also examined changes in the expression of muscarinic receptor subtype 3 (M3), β3 adrenoceptors, and purinergic P2X1 and P2X3 receptors in the urinary bladder using immunohistochemistry. Specifically, it was examined how these differ when celecoxib, BAY 60-2770 and a combination of celecoxib and BAY 60-2770 had been administered during the development of prostate inflammation in the rat model of CP/CPPS. The data show an upregulation of M3 receptors in animals with...
Therapy of epilepsy in dogs and cats
Šenková, Monika ; Vokřál, Ivan (advisor) ; Lecová, Lenka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Monika Šenková Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Therapy of epilepsy in dogs and cats Epilepsy is a common neurological disorder affecting dogs and cats. This chronic disorder is manifested by recurrent epileptic seizures. The true prevalence of epilepsy in dogs and cats is unknown. It is estimated to be 0,6-0,75 % in general dog population, and 1-2 % in hospitalized dog population. There is no known estimate for general cat population, but it is estimated to be 0,5-3,5 % in hospitalized cat population. Genetic predisposition has been proved in several dog breeds, and in some breeds, it is assumed. Diagnostics of epilepsy could be often difficult, and it reflects only the symptoms described by the pet owner, therefore the close cooperation between the pet owner and the veterinarian is needed. The aims of the treatment are to decrease seizure frequency, duration, severity, and the total number of epileptic seizures that occurs with none or at least minimal adverse effects, to maximize the dog's and owner's quality of life. Currently, there is no guideline for choice of treatment and a final decision should be made on a case-by-case basis. Monotherapy is preferred...
Study of adenosine effects on proliferation of BeWo cell line
Papírník, Josef ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Josef Papírník Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Studium of adenosine on proiferation activity in BeWo cell line The placenta is a rapidly developing organ that provides nutrition, protection and environment for the growing fetus. Fetal development is dependent on the supply of nutrients from the mother's blood either by passive diffusion or mediated by transporters. One of the essential nutrients are nucleosides, which are known to promote DNA synthesis and thus the growth of certain tissues. In order to pass across the plasma membrane they need nukleoside transporters (NTs) because of its hydrophilic feature. Additionally Ado takes part in cell signaling. Its wide- ranging effects, including influencing proliferation, are mediated by its binding to adenosine receptors (ARs). The placenta expresses NTs and ARs, which means that it is equipped to uptake nucleosides from maternal blood and has ability to receive signals from the external environment via the adenosine molecule. However, the importance of nucleosides for placental growth has not been investigated yet. The aim of this thesis is to test the effect of nucleosides on the proliferation of...
Optimization of the method for viability testing in Haemonchus contortus
Mašátová, Eva ; Skálová, Lenka (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Eva Mašátová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Consultant: Mgr. Linh Thuy Nguyen Title of diploma thesis: Optimization of the method for viability testing in Haemonchus contortus Barber's pole worm (Haemonchus contortus) is one of the most widespread pathogenic nematodes of the Trichostrongylidae family parasitizing in the abomasum of small ruminants, mainly in sheep. The most common symptoms of haemonchosis are anaemia, lack of thriving and weight loss. Young animals can also die. A significant complication in the treatment of haemonchosis is the rapidly developing resistance of the barber's pole worm to the administered drugs, which has become a global problem in recent years. This work focused on testing the efficacy of benzimidazole anthelmintics (thiabendazole and albendazole) in three strains of barber's pole worm, which differ in their drug sensitivity. We worked with strains: ISE (Inbred Susceptible Edinburgh) strain - sensitive, IRE (Inbred Resistant Edinburgh) strain - resistant and WR (White-River) strain - multi- resistant. The egg hatch test (EHT) was used to monitor the drug effectiveness and thus to monitor the level of resistance. Eggs from individual strains were...
Placental homeostasis of monoamines; effect of gestation age
Mahrla, Filip ; Štaud, František (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Filip Mahrla Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: PharmDr. Rona Karahoda, Ph.D. Title of diploma thesis: Placental homeostasis of monoamines; effect of gestation age Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence suggests their involvement in placental development and functions and a crucial role in fetal development and programming. Nonetheless, a comprehensive characterization of catecholamine synthesis, degradation, and transport in the fetoplacental unit is still lacking. Thus, in this thesis, we aimed to provide a comprehensive evaluation of catecholamine metabolism and transport in the fetoplacental unit. Gene and protein expression was evaluated using quantitative polymerase chain reaction (PCR) and Western blot analysis, respectively. Firstly, using several placental cell models (BeWo, JEG-3, primary trophoblast cells), we identified components of cellular catecholamine handling associated with the trophoblast cells. Next, we determined the effect of advancing gestation on the placental catecholamine system in humans (first trimester vs. term placenta) and...
Current role of veterinary drugs in pharmacy
Galambicová, Eliška ; Vokřál, Ivan (advisor) ; Ťupová, Lenka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Eliška Galambicová Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Current role of veterinary drugs in pharmacy The aim of this diploma thesis is to chart the current role of veterinary drugs in the range of pharmacies and the knowledge of pharmacists in the field of veterinary drugs. Data was collected via questionnaire from March to May 2021 and the target group was graduates in the field of pharmacy. A total of 2,148 pharmacies across the Czech Republic were contacted via an e-mail obtained from the website of the State Institute of Drug Control. The anonymous questionnaire consisted of a total of 15 questions which focused on mass-produced veterinary medicinal products and individually prepared veterinary medicinal products, human drugs used in veterinary care, a background of knowledge of pharmacists in the field and information that pharmacists consider important which was not acquired throughout their studies. A total of 325 completed questionnaires were obtained within the survey, while the array of pharmacies that completed the questionnaire was approximately even throughout the Czech Republic. The results showed that 92.3 % of the surveyed pharmacies across the Czech...
Organ distribution of anionic phthalocyanine photosensitizers in a mouse tumor model.
Kožená, Iva ; Macháček, Miloslav (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Author: Bc. Iva Kožená Supervisor: RNDr. Miloslav Macháček, Ph.D. Consultant: PharmDr. Jan Kollár, Ph.D. Title of diploma thesis: Organ distribution of anionic phthalocyanine photosensitizers in a mouse tumor model Cancer treatment currently consists mainly of chemotherapy, radiotherapy, and surgery. As these treatments possess certain side effects, other ways of treating cancer are being explored. One of these modern approaches, which is the subject of intensive research around the world, is a non-invasive and minimally toxic method called photodynamic therapy (PDT). The PDT is based on the application of a light-sensitive substance called a photosensitiser (PS), which accumulates selectively in the tumour and, after exposure to a light of a suitable wavelength, a photochemical reaction occurs which leads to the production of reactive oxygen species. The result of this reaction is an oxidative stress in the tumour tissue together with cellular damage with subsequent cell death accompanied with vascular damage, and even stimulation of the immune response. Due to their advantageous properties, the phthalocyanines (Pcs) are very promising PSs. They are usually prepared in the form of complexes with centrally...
Defence mechanisms of lancet fluke against effects of anthelmintics
Ballóková, Anna ; Szotáková, Barbora (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Anna Ballóková Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Defence mechanisms of lancet fluke against effects of anthelmintics Dicroceliosis, helminthosis caused by Dicrocoelium dendriticum (lancet fluke), is worldwide spread infection of small ruminants. The only way of effective control of this parasitosis is in administration of anthelmintics. In lancet fluke, benzimidazole anthelmintic albendazole metabolism via enzymatic sulfoxidation was found but no information about albendazole oxidases is available. The aim of this work was to identify enzymes involved in the metabolism of albendazole in Dicrocoelium dendriticum isolated from naturally infected mouflons (Ovis musimon). To determinate the involved enzymes some of the specific inhibitors were used. The only effective inhibitors used in this work were α-nafthylthiourea and methimazole, specific inhibitors of flavin-containing monooxygenases. Indole-3-carbinole, used as the specific inhibitor of the same enzymatic system, was without any effect. Other inhibitors were used: 3-amino-1,2,4-triazole for catalase, diethyldithiocarbamate and octylamine for cytochrome P450 and salicylohydroxamic acid and...
Evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of tumorous diseases.
Půlkrábková, Martina ; Macháček, Miloslav (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Martina Půlkrábková Supervisor: Mgr. Miloslav Macháček, Ph.D. Title of diploma thesis: Evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of tumorous diseases. Cancerous diseases are one of the most common causes of death, especially in industrialized countries. Their more effective treatment requires development of new potential anti-tumor agents and therapeutic methods. Photodynamic therapy (PDT) is a clinically approved method for the treatment of both tumorous and some other diseases. Its main advantages are non-invasiveness and potential for high selectivity to target cells, which distinguishes it from current conventional anticancer treatments (chemotherapy, radiotherapy). The effect of PDT is based on a combination of three effective components - molecular oxygen, light and photosensitiser (PS). These substances are inherently non-toxic, but they can form reactive oxygen species (ROS) if combined. Then, ROS significantly damages cellular structures in target cells, which can result in cell death. PS is a substance capable of absorbing light of suitable wavelength and transferring the received energy to surrounding molecules, to molecular oxygen in...

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