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Interactions of drugs used to treat schizophrenia and their accompanying symptoms
Musilová, Jana ; Janoušek, Oto (referee) ; Cicková, Pavlína (advisor)
The thesis studies interactions and side effects of antipsychotic drugs. It describes the drug discovery and related scientific fields - especially the field of biological network analysis. The thesis also describes schizophrenia and its treatment. The aim of the work is creating script in R language for automatic data download from open source databases and a search of the most significant drug interactions in data from the open source databases, based on the visualisation and analysis of networks with Cytoscape software and its plugins, and a specification of similar pharmacological features of the most important medicaments.
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Drug repurposing for the inhibition of invasiveness and metastasis of cancer cells
Turchyna, Kateryna ; Brábek, Jan (advisor) ; Jakubek, Milan (referee)
Metastasis is the primary cause of death from cancer. Current lack of medicines for metastasis makes it a topical issue and encourages the global search for molecules that may potentially inhibit invasiveness of cancer cells, and thus prevent metastatic spread. Drug repurposing is a strategy of identifying new uses for approved drugs that are outside the scope of the original medical indication. The aim of this thesis is to summarize knowledge on the repurposing potential of selected groups of drugs with emphasis on molecular mechanisms of their action. In particular, the work is focused on selected antipsychotics, antidepressants, beta- blockers and statins, whose abilities to inhibit cancer invasiveness have been indicated.
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Embryotoxicity testing of psychopharmacs using the CHEST method
Pavlovič, Ondřej ; Peterka, Miroslav (advisor) ; Maňáková, Eva (referee)
Psychotropic drugs are commonly used group of pharmaceuticals, their main effect is to alter psychic condition, including mental diseases treatment. Symptoms of mental illnesses are more and more common, theref orenumber of patients diagnosed with mental illnes, and thus using psychotropics, is growing stronger. But using psychotropics during gestation is not without risks for mother and embryo itself. However, thanks to the absence of controlled human studies, the knowledge of emrbyotoxic effects of pschotropics is limited to casuistics, reported side effects and animal experimental studies. Many of those studies suggests emrbyotoxic potential of psychotropic drugs, on the other hand, others claim their safety. The goal of this thesis is to test at least some of them, using CHEST method, that allows us to observe direct effect of unmetabolized substance on chick embryo. In this thesis we tested selected psychotropics, very common antidepressant fluoxetine (prozac) and antipsychotic drug olanzapine, for embryotoxicity, using in ovo method CHEST with chick embryos as model organism. By bypassing the maternal organism and his metabolism, this method allows to observe direct effect of unmetabolized substance on chick embryo. Results revealed embryotoxic effect of fluoxetin in dosage 10-2 and 10-3 on 3rd and...
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Psychopathology of early-onset schizophrenia and its therapy with focus on atypical neuroleptics
Koblic Zedková, Iveta ; Hrdlička, Michal (advisor) ; Bareš, Martin (referee) ; Stárková, Libuše (referee)
OBJECTIVES: The aim of our study was to assess clinical presentation of early-onset schizophrenia spectrum disoders (EO-SSD), the time to first improvement and efficacy associated with selected atypical (AAPs) and typical (TAPs) antipsychotics, as well as two main side effects - weight gain and treatment-emergent extrapyramidal symptoms (EPSs) during the treatment in patients with EO-SSD. METHODS: This was a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs (risperidone, olanzapine, ziprasidone, quetiapine and clozapine) and TAPs (haloperidol, perphenazine and sulpiride), for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 173 patients (85 males, 88 females; mean age 15.8±1.6 years); their treatment included 297 treatment trials. Data on premorbid adjustment, prodromal symptoms and psychopathology at admission, as well as comorbidity were evaluated based on the patients' medical records. The time to first improvement could be estimated in 258 treatment trials; of these, 195 (76%) comprised AAPs and 63 (24%) TAPs. The time to first improvement was assessed in agreement with the methodology established for retrospective studies as the number of treatment days prior to the first record of improvement...
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Splitting and Dissociation in Schizophrenia
Pěč, Ondřej ; Raboch, Jiří (advisor) ; Šípek, Jiří (referee) ; Kocourková, Jana (referee)
The term splitting is defined as a process of formation of mental aggregates linked incompatible experiences producing numerous divisions in mental apparatus. Current findings indicate that psychological splitting in schizophrenia is likely specifically presented on a neural level as disrupted organization in neural communication. This disrupted neural communication likely underlies deficits in mental processing described by various neuroscientific concepts such as theories of disturbed connectivity, corollary discharges and dynamic complexity. In this context, a purpose of the theoretical part of the dissertation is to describe basic neuroscience theories that complementarily reflect interrelated processes between mind and brain underlying disturbances of mental integration that likely present a neural representation of the splitting. A purpose of the first part of the empirical research was to examine relationships between psychological process of splitting and disturbed cognitive and affective functions in schizophrenia. A sample of patients with borderline personality disorder (BPD) was used as a control group in this study. Methods: In the clinical study, we have assessed 30 patients with schizophrenia and 35 patients with BPD. The symptoms of splitting were measured using self- reported...
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The effect of psychotropic drugs on the mitochondrial functions.
Cikánková, Tereza ; Rečková Hroudová, Jana (advisor) ; Herink, Josef (referee) ; Vaňhara, Petr (referee)
Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...
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Embryotoxicity testing of psychopharmacs using the CHEST method
Pavlovič, Ondřej ; Peterka, Miroslav (advisor) ; Maňáková, Eva (referee)
Psychotropic drugs are commonly used group of pharmaceuticals, their main effect is to alter psychic condition, including mental diseases treatment. Symptoms of mental illnesses are more and more common, theref orenumber of patients diagnosed with mental illnes, and thus using psychotropics, is growing stronger. But using psychotropics during gestation is not without risks for mother and embryo itself. However, thanks to the absence of controlled human studies, the knowledge of emrbyotoxic effects of pschotropics is limited to casuistics, reported side effects and animal experimental studies. Many of those studies suggests emrbyotoxic potential of psychotropic drugs, on the other hand, others claim their safety. The goal of this thesis is to test at least some of them, using CHEST method, that allows us to observe direct effect of unmetabolized substance on chick embryo. In this thesis we tested selected psychotropics, very common antidepressant fluoxetine (prozac) and antipsychotic drug olanzapine, for embryotoxicity, using in ovo method CHEST with chick embryos as model organism. By bypassing the maternal organism and his metabolism, this method allows to observe direct effect of unmetabolized substance on chick embryo. Results revealed embryotoxic effect of fluoxetin in dosage 10-2 and 10-3 on 3rd and...
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Splitting and Dissociation in Schizophrenia
Pěč, Ondřej ; Raboch, Jiří (advisor) ; Šípek, Jiří (referee) ; Kocourková, Jana (referee)
The term splitting is defined as a process of formation of mental aggregates linked incompatible experiences producing numerous divisions in mental apparatus. Current findings indicate that psychological splitting in schizophrenia is likely specifically presented on a neural level as disrupted organization in neural communication. This disrupted neural communication likely underlies deficits in mental processing described by various neuroscientific concepts such as theories of disturbed connectivity, corollary discharges and dynamic complexity. In this context, a purpose of the theoretical part of the dissertation is to describe basic neuroscience theories that complementarily reflect interrelated processes between mind and brain underlying disturbances of mental integration that likely present a neural representation of the splitting. A purpose of the first part of the empirical research was to examine relationships between psychological process of splitting and disturbed cognitive and affective functions in schizophrenia. A sample of patients with borderline personality disorder (BPD) was used as a control group in this study. Methods: In the clinical study, we have assessed 30 patients with schizophrenia and 35 patients with BPD. The symptoms of splitting were measured using self- reported...
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Treatment of schizophrenia
Hlinková, Lucie ; Hrdina, Radomír (advisor) ; Herink, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucie Hlinková Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Treatment of schizophrenia Schizophrenia is a serious mental disease, mostly chronic. It affects about 1 % of population, first episode of the disease occurs mostly between the age of 15 and 35. It manifests itself with disorders of perception, behavior and thinking. The specific symptoms include hallucinations, delusions, disorganized speech and behavior, catatonia, disorders of attention and volition and social withdrawal. Etiopathogenesis of schizophrenia is likely affected by both genetic and environmental factors, the true cause of the disease has not been discovered yet. The goal of the treatment is to improve the patient's quality of life and prevent the occurrence of relapses. Drugs acting on the dopaminergic system are effective in the treatment of schizophrenia, where as antagonists bind to the dopamine receptors. These medicines are called antipsychotics, they are divided into two generations. The first generation is characterized by high affinity mainly for dopamine receptors, the second one in addition by binding to serotonin receptors. Each class of antipsychotics is characterized by the...
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Interactions of drugs used to treat schizophrenia and their accompanying symptoms
Musilová, Jana ; Janoušek, Oto (referee) ; Cicková, Pavlína (advisor)
The thesis studies interactions and side effects of antipsychotic drugs. It describes the drug discovery and related scientific fields - especially the field of biological network analysis. The thesis also describes schizophrenia and its treatment. The aim of the work is creating script in R language for automatic data download from open source databases and a search of the most significant drug interactions in data from the open source databases, based on the visualisation and analysis of networks with Cytoscape software and its plugins, and a specification of similar pharmacological features of the most important medicaments.
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