HIV-1 protease plays a crucial role in the late state of the life cycle of HIV virus when it cleaves the viral polyprotein precursors into the structural and functional proteins. If it is effectively inhibited, HIV particles remain immature and noninfectious. The application of highly active antiretroviral therapy (HAART) including protease inhibitors can reduce plasma HIV-1 levels below the detection limit in adherent patients and thus dramatically change their life expectancy. The clinical utility of the first inhibitors was limited by severe side effects, low bioavailability, high pill burdens, and rapid development of viral resistance under the selection pressure of HIV antiretrovirals. To overcome these difficulties, second-generation inhibitors were developed. Despite an indisputable improvement they brought to antiretroviral therapy, the development of new highly active HIV-1 protease inhibitors with optimal pharmacokinetic properties, higher metabolic stability, little off-target activity, and particularly, more favorable resistance profiles is still of high importance. This thesis provides an overview of anti-HIV- drugs including development of substituted metallacarboranes, a new class of potent, unusual, nonpeptidic HIV protease inhibitors with therapeutic potential. Next, the impact of...

GEMMOTHERAPY AND ITS USE IN PRACTISE Student: Škodová Adriana Tutor: PharmDr. Jitka Pokladníková, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Czech Republic Introduction: Gemmotherapy or budding medicine is an herbal healing method, whose roots go back to the Middle Ages and folk healing. It uses germ-shaped parts of plants (especially buds) for the production of liqueur glycerin macerates, which are proven to contain larger quantities of some important substances with healing properties than adult parts of plants. Objectives: The aim of this work was to summarize basic information about gemmotherapy from available literature; to summarize the description of the traditional use of selected plants and gemmotherapeutics prepared therefrom; to provide a summary of studies based on evidence-based literature, especially with regard to content and confirmatory medicinal properties, adverse effects, drug interactions and contraindications. Methods: General information about gemmotherapy was mainly drawn from books available in the Czech language. Data collection took place from October 2016 to August 2017, and researches based on literature were mainly based on the electronic databases PubMed, Web of Science, Wiley Online Library,...

The doctoral thesis tries to reflect the collaboration of Catholic priest with the State Security Service (ŠtB). This is done in two steps. The first part illustrates the historical background based on research of archive materials and testimony of living priests - agents. Results of historical research tell us that it is not possible to assess the collaboration across the board just on the registration of agents in secret police register. Core of historical part is a typology of collaboration. It serves as a base for input to the second ethical part of doctoral thesis. The main goal of ethical part is to find objective criterions for answerable and ethical way out from moral dilemmas. Core of this part is theory about ethical compromise with two normative principles - principle of small evil and principle of double effect. The analysis of small evil didn't get a satisfy way out from the situation of blackmail: in the concrete situation it didn't tell us, which evil is smaller and which is bigger. The principle of double effect showed us, that the collaboration in blackmail situation is without proportionate cause, in other words, is counterproductive to their value in universal perspective. The priests hadn't any guaranty, that after consent with collaboration in blackmail, the damage on their side but...

Restricting the effects of a patent These theses are focused on issues of the legal options on the exceptions and limitations to patent rights. At first there is clarified fundamental terminology, especially relation between terms patent and innovation, patentable solution and also effects of the patent. Next chapters relate to the limitation on the patent effects that is the experimental use exception and also so- called Bolar exception; using the invention for non-commercial purposes; institute of compulsory licences; limitation to extemporaneous preparation of medicines in pharmacy, use of patent law articles on foreign vessels, aircrafts, land vehicles not permanently accessing from foreign countries and institute of prior user rights. The author discusses non-commercial use of the invention, which is closely related to the experimental use exception in some countries or the legal institute of compulsory licenses, contemplating negative and positive impacts and moral aspects of that decision. Regarding the scope of the experimental use exception, the author argues that the exception in need is rather narrow rather than broader. In case of compulsory licences, the author is emphasising on fair balance between the interest of patent owner rights and the concerns of nation and also comes with...

Effects of {$\alpha$}1, {$\alpha$}2, {$\beta$}3 adrenergic agonists on resting oxygen consumption and effects of {$\alpha$} and {$\beta$}2 adrenergic antagonists on noradrenaline stimulated oxygen consumption of the human peripheral blood mononuclear cells (PBMC) were studied using the Clark oxygen electrode. It was found that, the {$\alpha$}2 agonist increases slightly the resting oxygen consumption in the PBMC while, the {$\beta$}2 and the {$\alpha$} antagonists inhibit the noradrenaline stimulated oxygen consumption considerably. The {$\alpha$}1 and {$\beta$}3 agonists have no effect on the resting oxygen consumption. The NA termogenesis in the PBMC is mediated by {$\beta$}1 (25%), {$\beta$}2 (8%) and {$\alpha$}2 (12%) adrenergic receptors and not by {$\beta$}3 adrenoreceptors. The NA thermogenesis in the PBMC is mediated by different adrenoreceptors than the NA thermogenesis in the brown adipose tissue. The NA thermogenesis of PBMC is independent on the presence of organic substrates in the cultivation medium. Administration of external substrates (glucose, glutamine, methionine) to the medium has no effect on resting and NA stimulated oxygen consumption of PBMC, while administration of cysteine increases NA stimulated oxygen consumption considerably, indicating that acetyl-CoA could be an important substrate for NA thermogenesis in PBMC.

This thesis assesses the effectiveness of shock wave therapy for dysfunctional disorders of the musculoskeletal system. While we are well aware of the physical principles and history of shock wave generators, opinion differs on the treatment effectiveness mechanisms. The theoretical part of this work explains the effects of shock waves on various types of tissue, the differentiation of the cells, and the analgetic effect of therapy. It summarizes the indications, side effects and contraindications of shock wave therapy. The research part of this thesis deals with the effectiveness of shock wave therapy at the Department of Rehabilitation and Sports Medicine at the Motol University Hospital, which specialises in various musculoskeletal disorders. This thesis evaluates the correlation between the effectiveness of shock wave therapy and length of time the patient has experienced difficulties before undergoing treatment. This thesis also reviews whether the number of treatment applications has the capability to influence the outcome of therapy. The study is controlled by a control group of 22 patients. The total effectiveness of shock wave therapy is p = 1,12*10-10 . The shock wave therapy effectiveness of patients with heel spur is p = 0,00176. The shock wave therapy effectiveness of patients with...

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...

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...

THE TITLE OF THE DIPLOMA THESIS AND ABSTRACT TITLE: Transaction Avoidance in Insolvency Proceedings Comparison of Czech and British Legislation ABSTRACT: The general goal of transaction avoidance in insolvency proceedings is to prevent the adverse effects of economic entity's collapse that might be multiplied both by an interest of the collapsing entity to dispose the residual property to connected or associated subjects and by a plurality of creditors with conflicting interests and logical motivation not to be subjected to the mandatory rules of the insolvency proceedings. The current attitude and status of Czech legislation and jurisprudence to transaction avoidance is affected by the fact that within the socialism (and the related decadence of jurisprudence) this legislation could not sufficiently evolve which resulted in a situation that Czech legislation is currently dealing with multiple theoretical and practical deficiencies that neighboring legal systems have dealt with many decades ago. The main goal of this theses is to provide thorough analysis of both Czech and (with regards to the content limit of this theses) also the British legislation and to point out the most crucial deficiencies in Czech legislation and possible inspiration in the British legislation. The theses is divided into four...

The subject of research were effect of elevated water level in the downstream apron on the weir flow capacity and load characteristics of the flap gate. The thesis is focused on possibilities of physical and CFD modeling of flap gate weir flow. In the introduction are contained current condition of knowledge, perfomed model studies conducted in the Czech republic and abroad, as well as flap weirs realized in our country and in the world. This is followed by experimental physical research on family of weir structure models in scales 1:1 (prototype), 1:2 and 1:2.5. Options CFD simulations a flap gate weir are contained in chapter of CFD modeling. In conclusion are compared physical methods with CFD simulations on flap gate weir.