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Growth of human osteoblasts SaOS2 on titanium modified with nanotubes.
Krýslová, Markéta ; Filová, Elena (advisor) ; Melkes, Barbora (referee)
This work summarizes information about the interactions between osteoblasts and nanostructured materials, which are of growing importance and are highly promising in regard to their application in medicine and in tissue engineering. The number of people with artificial replacements of tissues, such as bones, joints, teeth, cartilage, and tendons increases every year. Titanium and his alloys are extensively used for artificial tissue replacements. Titanium is favourable for its mechanical properties that allow the implant to remain in the place of implantation more than thirty years. For better osseointegration the surface of titanium can be modified with hydroxyapatite, coating with diamond-like carbon or plasma spray coating. Another option is to prepare a layer of nanotubes, which forms nanoroughness on material surface. The nanoroughness in turn improves physical and chemical properties of the material surface. Nanostructured materials mimic the natural bone tissue, support adsorption of specific proteins, improve the biocompatibility of the implants and positively influence cell behaviour, e.g. stimulate the synthesis and suitable conformation of specific molecules for cell adhesion and differentiation.
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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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Functions of the adult neurogenesis
Šejnová, Gabriela ; Stuchlík, Aleš (advisor) ; Melkes, Barbora (referee)
Neurogenesis in adult mammals was first discovered in the second half of the 20th century and its mechanisms, regulation and possible functions have been researched eversince. Scientists have so far been able to describe the process of neuronal development as well as some possible influences. However, the role of this phenomenon is still being discussed. This thesis is focused on neurogenesis in the dentate gyrus in hippocampus, a pair structure located in the central part of the temporal lobe. The main aim is to describe the recent findings and research models as well as the assumed functions. The most recent theories find the role of hippocampal neurogenesis in pattern separation, memory resolution, contextual memory or memory consolidation. These hypotheses are quite variable due to the broad range of research methods and their interpretations, however, none of them seems to disprove the others. Key words: neurogenesis, functions, behavior, hippocampus, learning
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Effect of intestinal microflora on the activity of higher brain centers
Arnold, Tomáš ; Hock, Miroslav (advisor) ; Melkes, Barbora (referee)
Abstract Intestinal microflora consists of large bacterial community that resides in the intestines, especially the colon, and lives in symbiosis with the host. It consists mainly representatives of the four bacterial strains (Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria). It has already been shown that the proportional representation of the bacterial strains in time does not change much, but the research of the last decade have shown irrefutable effect between the change of diet and composition of the intestinal microflora. In addition, there is evidence of changes in the representation of bacterial strains in the course of development of certain intestinal pathologies such as inflammatory bowel disease. More and more are starting to emerge papers describing the influence of altered intestinal microflora respectively its representatives, on the activity and function of the CNS. This interaction of the digestive system and CNS seems to be bidirectional and mediated by several different pathways. Finally, it shows that dysbiosis of the intestinal microflora promotes anxiety and depression that can lead to the urge to prematurely terminate life. The aim of this work is to provide a comprehensive view of this relatively young, but also very interesting...
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Studies on molecular interactions of the mu-opioid and TRPV1 receptors
Melkes, Barbora ; Novotný, Jiří (advisor) ; Blahoš, Jaroslav (referee) ; Krůšek, Jan (referee)
In this work, we investigated the behavior of the -opioid receptor (MOR) and the transient receptor potential vanilloid 1 (TRPV1) ion channel in the plasma membrane and their mutual communication. Both these receptors are implicated in pain perception and analgesia. We observed that the lateral mobility of MOR was strongly affected by different biased opioid agonists. DAMGO and endomorphin-2 display opposite bias towards MOR. According to our results, they also have the opposite effects on the mobility of MOR. Morphine induced only small changes in the mobility of MOR. Moreover, cholesterol depletion and blockage of G protein signaling by pertussis toxin (PTX) affected the ability of different MOR agonists to alter MOR mobility in a unique manner. The effects of DAMGO and endomorphin-2 were compromised under these conditions. On the other hand, we observed increased movement of MOR after the addition of morphine. PTX alone did not affect receptor movement, but it completely disrupted the effect of cholesterol depletion on morphine induced changes the mobility of MOR. Next we studied the mobility of TRPV1. The TRPV1 agonist capsaicin changed the lateral mobility of TRPV1. Surprisingly, after adding the MOR antagonist naloxone, the apparent diffusion coefficient of TRPV1 but to a lower extent than...
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Immune mechanisms in inflammatory pain
Vašek, Daniel ; Krulová, Magdaléna (advisor) ; Melkes, Barbora (referee)
Pain is one of the five symptoms of inflammation. Activation and regulation of pain are affected both by the nervous system and the immune system. The production of inflammatory mediators decreases the threshold for activation of the ion channels of peripheral nociceptors, which then result in painful sensations caused by otherwise innocuous stimuli. Such mediators are cytokines, bradykinin, prostaglandins or various neurotrophic factors. This work aims to explain the function of immune cells in the production of these inflammatory and painful modulators. The study of activation and sensitization of nociceptors in inflammation is important for the understanding of the whole mechanism of inflammatory pain as well as for a comprehensive understanding of the neuroimmune system. Understanding inflammatory pain can lead to the development of specific drugs against it. Key words: inflammation, pain, inflammatory pain, immune system, neuroimmune system
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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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Effect of intestinal microflora on the activity of higher brain centers
Arnold, Tomáš ; Hock, Miroslav (advisor) ; Melkes, Barbora (referee)
Abstract Intestinal microflora consists of large bacterial community that resides in the intestines, especially the colon, and lives in symbiosis with the host. It consists mainly representatives of the four bacterial strains (Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria). It has already been shown that the proportional representation of the bacterial strains in time does not change much, but the research of the last decade have shown irrefutable effect between the change of diet and composition of the intestinal microflora. In addition, there is evidence of changes in the representation of bacterial strains in the course of development of certain intestinal pathologies such as inflammatory bowel disease. More and more are starting to emerge papers describing the influence of altered intestinal microflora respectively its representatives, on the activity and function of the CNS. This interaction of the digestive system and CNS seems to be bidirectional and mediated by several different pathways. Finally, it shows that dysbiosis of the intestinal microflora promotes anxiety and depression that can lead to the urge to prematurely terminate life. The aim of this work is to provide a comprehensive view of this relatively young, but also very interesting...
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Functions of the adult neurogenesis
Šejnová, Gabriela ; Stuchlík, Aleš (advisor) ; Melkes, Barbora (referee)
Neurogenesis in adult mammals was first discovered in the second half of the 20th century and its mechanisms, regulation and possible functions have been researched eversince. Scientists have so far been able to describe the process of neuronal development as well as some possible influences. However, the role of this phenomenon is still being discussed. This thesis is focused on neurogenesis in the dentate gyrus in hippocampus, a pair structure located in the central part of the temporal lobe. The main aim is to describe the recent findings and research models as well as the assumed functions. The most recent theories find the role of hippocampal neurogenesis in pattern separation, memory resolution, contextual memory or memory consolidation. These hypotheses are quite variable due to the broad range of research methods and their interpretations, however, none of them seems to disprove the others. Key words: neurogenesis, functions, behavior, hippocampus, learning
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Methadone Maintenance Treatment - The pharmacokinetics and the pharmacodynamics as a basis.
Pajorová, Júlia ; Hejnová, Lucie (advisor) ; Melkes, Barbora (referee)
The aim of this study was to summarize the pharmacokinetic and pharmacodynamic knowledge about methadone, and to compare it with morphine on both molecular and clinical level. Methadone and morphine are μ opioid agonists, and therefore their effect on the organism is similar. However, the existence of fundamental differences between them, is decisive for their use in clinical practice. It was discovered that on a molecular level, methadone has a higher efficiency to internalise μ receptors than morphine, moreover it's potential to form addiction and tolerance is lower. From a pharmacokinetic point of view, methadone in contrary to morphine has a much longer elimination half-life, which brings a lots of benefits and lots of disadvantages. One of the benefits is longer effect, which together with the lower potential for tolerance and addiction development, predetermined methadone to be used for maintenance therapy for patients addicted to opiates. Maintenance therapy is based on the replacement of an illegal drug (mainly heroine), for an opiate of similar nature, which on the other hand has more favourable effects on the patient (methadone). The purpose of it is to ease the development of withdrawal symptoms during therapy's first stages, and with gradual lowering of methadone dosage, to lead the...
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