The mortality of cardiovascular diseases remains high and it likely tends to increase in the future. Although many ways how to increase the resistance against myocardial ischemia- reperfusion damage have been described, few of them were transferred into clinical practice. Cardioprotective effect of chronic hypoxia has been described during 60s of the last century. Its detailed mechanism has not been elucidated, but a number of components has been identified. One of these components presents protein kinase C (PKC). The role of PKC was described in detail in the mechanism of ischemic preconditioning, but its involvement in the mechanism of cardioprotection induced by chronic hypoxia remains unclear. One reason is the amount of PKC isoforms, which have often contradictory effects, and the diversity of hypoxic models used. The most frequently mentioned isoforms in connection with cardioprotection are PKCδ and PKCε. The aim of my thesis was to analyze changes in these PKC isoforms at two different cardioprotective models of hypoxia - intermittent hypobaric (IHH) and continuous normobaric hypoxia (CNH). We also examined the target proteins of PKCδ and PKCε after the adaptation to IHH, which could be involved in the mechanism of cardioprotection. These included proteins associated with apoptosis and...

Schizophrenia is a serious neuropsychiatric disease with a lifetime prevalence of 1% and it disrupts almost all mental functions. It manifests with many symptoms, which can be roughly classified into three main classes - positive, negative and cognitive dysfunctions. The psychosis, which can be often seen in schizophrenia, is a very serious problem that along with all other symptoms influences the patients' clinical status as well as quality of their life. As no direct causes or causal treatments for schizophrenia are known, scientist often focus on animal models of schizophrenia as tools for investigating mechanisms that can take a part in real disease and for seeking novel antipsychotics. This thesis aims at investigating two-week subchronic treatment with dizocilpine (MK-801), a non-competitive antagonist of NMDA receptors, in Wistar and Long-Evans rats aged 30 (PND 30) and 60 days (PND 60) at the onset of the treatment. Subsequently, long-term neurobehavioral consequences of this experimental psychosis were studied by testing rats at three behavioral tasks: the Elevated-plus maze (EPM), the Morris water maze (MWM) and active place avoidance on a rotating arena (Carousel). The Western blot method was used to determine post-mortem changes in expression of the NR1, NR2A and NR2B subunits of the...

By using panel data from SHARE this thesis shows, that retirement has a negative effect on indicators of physical and mental health. Results from using fixed effects models suggest that retirement leads to 0,85 points increase in chronic diseases, 0,3 points increase in difficulties associated with mobility and 0,07 points increase in body mass index. Also retirement increases the level of depression by 0,5 points. According to the results, the effect of retirement on memory is also negative.

Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...

1 Abstract BCR/ABL is a constitutively active tyrosine kinase that has been shown to be at the heart of the development of chronic myeloid leukemia (CML) and about 30% of acute lymphoblastic leukemia (ALL). With the recent advent of tyrosine kinase inhibitors (TKIs), exemplified by Imatinib, Nilotinib, Dasatinib and Bosutinib, patients with Ph+ CML or ALL are candidates for the therapy with these agents. From the available TKIs, Imatinib is considered as front-line therapy for CML patients in chronic phase, while for Ph+ ALL patients, 2nd generation TKIs (nilotinib, dasatinib, bosutinib) might be considered as more effective therapeutic option. Since the treatment with TKIs is a long-term affair, a substantial proportion of patients acquire some sort of mutation in kinase domain of BCR- ABL, which could be a reason of treatment failure. To date, over ninety BCR/ABL kinase domain mutations have been identified, affecting over 50 amino acids. Recurrent BCR/ABL kinase domain mutations have already been in vitro tested to approximate for their in vivo behavior. Our goal is to invent in vitro technique that would allow testing TKI sensitivity of novel BCR/ABL kinase domain mutations, identified at very low MRD levels. The technique makes use of site-directed mutagenesis to create the novel BCR/ABL kinase domain...

This thesis researches the efficacy of binaural beats for the treatment of chronic non-tumoral pain. The thesis is divided into theoretical and empirical part. The theoretical part discusses the impact of chronic pain on quality of life, psychological aspects of chronic pain and the changes in behaviour. The focus is on the treatment of chronic pain and its limitations. Binaural beats are presented as a new tool for treatment of chronic pain. The empirical part consists of the experiment focused on the effect of theta rhythm binaural beats on participants with chronic non-tumoral pain. The experiment was conducted at Klinika rehabilitace a tělovýchovného lékařství 2.LF UK a FNM. The sample size was 90 participants (N=90). Participants were divided into two groups- with intervention and without intervention. Participants with intervention listened binaural beats for 20 minutes, three times on average during their hospitalization. VAS, GAD- 7, BDI-II, TSK-CZ, Oswestry Disability Index and Emotion Thermometers methods were used. The first measurement took place before the hospitalization, the second before the intervention with binaural beats, then immediately after the intervention and at the end of hospitalization. The main aim of this study was to investigate the efficacy of binaural beats in...

My diploma thesis deals with issues of gender relations and the construction of identities of lived experiences of parents caring for a child (children) with a chronic illness. For my qualitative research, I have chosen the method of semi-structured interviews with both parents of the child (children). Subsequent analysis of the data in this empirical study examines the way in which care for a child with chronic illness affects, due to its demanding character, gender relations and whether it leads to more balanced gender relations or vice versa. I also deal with the process of identifying both parents in the day care of a child with chronic illness in the context of a combination of paid work and home care and children. In my work, I see how my communication partners are conceptualizing the chronic illness of the child as a differentness and the care of a child with a chronic illness as a burden. I focus on the emotional plane of parenthood and also analyze the processes of negotiation within different institutions (health and education organizations, state authorities). Key words: Chronic illness, child, parenthood, differentness, burden, care, gender relations

This thesis focuses on the psychological factors that play a role in the development and maintenance of chronic postsurgical pain in patients after cardiac surgery. The literature review deals with the mechanisms of chronic postsurgical pain, its risk factors, the process of the transformartion of acute pain into chronic pain, and the psychological management of chronic pain after surgery, specifically in the field of cardiosurgery. The thesis focuses in particular on patient-related factors in terms of anxiety or depression before or after the surgery, coping strategies, fear of pain, attachment styles, and how are these factors involved in the development nad maintenance of chronic pain. The empirical part consists of a research of quantitative design conducted at the Department of Cardiac Surgery of the 3rd Faculty of Medicine and FN KV in Prague, which monitors the development of pain in patients after cardiac surgery at the time of discharge, 3 months after the surgery and after 1 year after the surgery, and focuses on the assessment of preoperative and postoperative patient-related factors that contribute to the development and maintenance of chronic pain. The main aim of the research is to identify these psychological factors.

Endogenous cardiac protection against acute ischemia/reperfusion injury can by increased by cardiac adaptation to various forms of chronic hypoxia. Chronic hypoxia induces a large variety of adaptive changes in the myocardium that could be considered as protective, but the exact mechanism of increased ischemic tolerance is unknown. Different studies suggest that catecholamine release and their effect on -adrenergic signaling after adaptation to chronic hypoxia contributes to cardioprotection. In this study we focused on characterization of -adrenergic receptors ( -ARs) in the myocardium of rats after adaptation to three different hypoxic conditions: 1. intermittent normobaric hypoxia - INH/R (23 h hypoxia, 1 h reoxygenation), 2. intermittent normobaric hypoxia - INH (8 h hypoxia, 16 h normoxia), 3. continuous normobaric hypoxia - CNH (24 h hypoxia). We compared how each hypoxic model affects the total number of -adrenergic receptors and proportion of individual subtypes ( 1-and 2-ARs) in the left and right ventricles compared control normoxic rats. The INH model had apparently no effect on -ARs in either ventricles. On the other hand, adaptation to INH/R and CNH was accompanied by a significant decrease (by about 25%) in the total number of -adrenergic receptors in the right ventricles. Our present...

Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...