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Curcumin in the treatment of traumatic spinal cord injury
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Martončíková, Marcela (referee)
Spinal cord injury is a very significant clinical as well as social problem with extensive consequences, affecting the patient and also his/her family. Great efforts have been devoted to searching for an effective treatment, which would improve their situation. This thesis evaluated the effects of the natural compound curcumin on spinal cord injury using an experimental balloon compression model. Male Wistar rats were randomized into two groups following the lesion induction, namely vehicle- or curcumin-treated. The behavioral recovery was evaluated using a set of locomotor and sensory tests and a histological and imunohistochemical analysis was performed. The qPCR method was used to observe the expression of some genes related to regeneration and immune response. It was demonstrated that curcumin improved locomotor recovery after the spinal cord injury, particularly in the early stages. Morphometric analysis of the gray and white matter sparing didn't confirm any differences between the two groups. Nevertheless, the glial scar formation was significantly reduced around the central part of the lesion in the curcumin treated group and also the NF-κB activity was substantially inhibited. The gene expression analysis demontrated downregulation of Gfap and Rantes genes and upregulation of the Irf5 gene...
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Cardioprotective effect of adaptations to hypoxia and cold: Connexin 43 and hexokinase 2
Kohútová, Jana ; Žurmanová, Jitka (advisor) ; Radošinská, Jana (referee) ; Barančík, Miroslav (referee)
Ventricular arrhythmias are the main cause of death worldwide. An increased incidence of arrhythmias in the heart of mammals is accompanied by a remodeling of the cellular distribution gap between the channels of mainly connexin 43 (Cx43). Recently has been demonstrated significant effect of mitochondria and their association with arrhythmogenesis. Various pathological conditions alter the expression and / or distribution of Cx43, depending on the phosphorylation status. but also on altering the association of hexokinase with mitochondria, which reduces the likelihood of apoptosis activation. Adaptation to intermittent hypobaric hypoxia potentiates endogenous pathways reducing the incidence of ventricular arteries, whereas continuous normobaric hypoxia does not have this effect. Another studied model is cold acclimatization, which has been known for several decades by known effects on human health. However, the heart study of these models in relation to Cx43 is missing. Our goal was to determine the expression of Cx43, phosphorylated Cx43 (p-Cx43) and hexokinase (HK1, HK2) and their distribution in cardiomyocytes. In addition, the expression of Cx43 upstream kinases, protein kinase A, protein kinase G, casein kinase 1 in normoxic and hypoxic left ventricles of rats, along with Cx43 distribution...
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Methods and consequences of some neurosurgical interventions in animal model and in human clinic. Pinealectomy and intracerebroventricular application.
Řezáčová, Lenka ; Tichý, Michal (advisor) ; Szárszoi, Ondrej (referee) ; Přibáň, Vladimír (referee)
Clinical surgical techniques of pinealectomy and intracerebroventricular (i.c.v) cannulation are still used in the clinic in indicated cases. In research, there is an effort to replace these classical surgical techniques by other means. However, these various new models often do not reflect the complexity of the functions taking place in the living organism as a whole. The thesis shows that these surgical techniques should be also a part of biomedical research in the future, as they still bring new important information. In the experiment, the pinealectomy can serve as a model of resection or depletion (removal of natural hormone secretion), while i.c.v. application of the active substance to the ventricles on the contrary as a model of addition or substitution. The practical part of the thesis is divided into 4 areas: A) pinealectomy - an animal models, B) pinealectomy - in the experiment, C) pinealectomy - in the clinical practice and D) intracerebroventricular application - in the experiment. The work describes in detail the surgical techniques and discuss possible consequences of pinealectomy in 6 animal species (and their comparison) and in humans. It also includes an experiment with pinealectomy in a rat and a clinical study in patients with pineal cyst and subsequent pinealectomy. The work...
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The role of beta1 adrenergic receptors in heart of cold acclimated rat
Liptáková, Andrea ; Žurmanová, Jitka (advisor) ; Nováková, Olga (referee)
During cold acclimation the heat production is shifted from shivering to non-shivering thermogenesis, which is mediated by adrenergic signaling. It has also been observed, that cold acclimation may increase the organismal resistence to pathological stimuli and may affect functional parameters of cardiovascular system. However, acute exposure to sever cold is often associated with detrimental effects on the body. We have recently shown that chronic exposure to cold increases the heart's resistance to ischemia-reperfusion injury without negative side effects when mild temperatures are used, however the mechanism of protection is not yet known. The aim of this work was to determine whether: i) if the sensitivity of the heart to ischemia changes already after the first day of cold exposure and does not show any negative effects, ii) if β1-adrenergic signaling plays a role in chronic regimen of cold-induced cardioprotection. The results of this work showed that i) one day of exposure to mild cold did not change the sensitivity of the heart to ischemia and ii) metoprolol treatment reduced the infarct size in the control group, but did not affect the heart of cold-adapted rats. Key words : Heart, rat, beta 1 adrenergic receptors, cold acclimation
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Intra-amniotic Inflammation in Women with Preterm Labor with Intact Membranes - Clinical and Experimental Aspects
Stráník, Jaroslav ; Kacerovská Musilová, Ivana (advisor) ; Šimetka, Ondřej (referee) ; Čečková, Martina (referee)
Preterm labor with intact membranes (PTL) is responsible for approximately 40% of all preterm deliveries. PTL is frequently complicated by intra-amniotic inflammation (IAI), characterized by the elevation of inflammatory mediators in the amniotic fluid. Based on the presence or absence of microbial invasion of the amniotic cavity (MIAC), two different clinical phenotypes of IAI are distinguished: i) intra-amniotic infection, when microorganisms are present in the amniotic fluid, and ii) sterile IAI, when there are no microorganisms in the amniotic fluid. The clinical severity of both phenotypes of IAI is underlined by their association with adverse neonatal outcomes. In addition to the presence or absence of MIAC, there are also differences between the phenotypes of IAI in terms of their intra-amniotic inflammatory status characteristics. The clinical part of this thesis has addressed these differences in women with PTL. The first specific aim of this clinical study was to determine the concentration of interleukin (IL)-6 in the cervical fluid of women with PTL complicated by intra-amniotic infection and sterile IAI. The second specific aim was to determine the concentration of IgGFc-binding protein (FcgammaBP) in the amniotic and cervical fluids of women with PTL complicated by intra-amniotic...
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Inflammation and cancer in germ-free vs. conventionally reared animals
Čaja, Fabián ; Vannucci, Luca Ernesto (advisor) ; Tlaskalová - Hogenová, Helena (referee) ; Smrž, Daniel (referee)
Inflammation is considered as one of the main defence mechanisms of the immune system against threats that occur in the body. When present in its acute form, minimal or no detectable subsequent damage of original affected tissue exists. The more pathological form, chronic inflammation, is associated with permanent damage of the tissue and typically a hallmark of various diseases such as ulcerative colitis or colon carcinogenesis. These two pathologies are evolving in the unique colon microenvironment, where intensive interaction between the host cells and bacteria is present. The aim of our study was to investigate the immunological (ELISA, FACS, RT-PCR) and structural (histology, confocal microscopy) changes in the colon mucosa of Wistar-AVN rats induced by dextran sodium sulphate (DSS) to produce colon colitis and by azoxymethane (AOM) to produce colon carcinogenesis. Conventional (CV) and also germ-free (GF) reared animals were used to investigate the effects of the mucosal inflammation activated by the administered inducers as well as the role of colon microbiota - as promoters of a continuous immune activation - in the modulation of immunity and collagen scaffold remodelling. Our results showed that even in the early period after the induction, both inducers produced a smouldering...
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The effect of stress on regulation and regeneration of glucocorticoids in animal models differing in response of hypothalamo-pituitary-adrenal axis
Vodička, Martin ; Pácha, Jiří (advisor) ; Svoboda, Jan (referee) ; Bendová, Zdeňka (referee)
Stress reaction is usually activated by the brain, when homeostasis is or perceived to be threatened. The stress signals are transmitted from the brain by two main branches; the sympathoadrenomedullary and the hypothalamo-pituitary-adrenal (HPA) axes and employ neural, humoral and immune pathways to cope with the stressor. Because of its potency, the stress reaction has to be precisely regulated. The HPA axis is regulated by feedback loops where its end product, corticosterone in laboratory rat and mouse, inhibits its activity. The effect of corticosterone does not depend only on the concentration of corticosterone but also on local metabolism of glucocorticoids via oxo-reduction catalyzed by the enzyme 11β -hydroxysteroid dehydrogenase 1 (encoded by the Hsd11b1 gene), which intracellularly regenerates active corticosterone from inactive 11-dehydrocorticosterone, or by extra-adrenal de novo steroidogenesis of glucocorticoids. We focused on analysis of stress response in experimental animals differing in HPA axis responsivity (Fischer 344 rats (F344) vs. Lewis rats (LEW) and germ-free (GF) vs. specific pathogen free mice (SPF)) with special emphasis on regulation of stress response, glucocorticoid regeneration and influence of gut microbiota. We found that stress modulated local regeneration of...
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The in vitro effects of selected substances on isolated rat aorta
Beránková, Anna ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Beránková Supervisor: PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The in vitro effects of selected substances on isolated rat aorta Flavonoids are a numerous group of secondary plant metabolites. Flavonoid compounds are substances widely extended in nature and many of them have a positive influence on human health, primarily for their vasodilatory, antioxidant and anti- inflammatory effects. Three substances were selected for this diploma theses: two substances of isoflavonoid group, genistin and genistein, and the end product of genistein metabolism, 4-ethylphenol. The aim of this work is examination of vasorelaxant effects of this substances in vitro. Vasorelaxing potential of tested substances was tested in vitro in isolated aortic rings of Wistar rat. The effect of increasing doses of individual substances in precontracted aortic rings with intact endothelium was measured. From the obtained values of vessel tension, the DRC curves and EC50 values were created. The results were evaluated. The results analysis shows, that genistein (EC50 2,903.10-5 M) had the most significant activity. Also genistin (EC50 4,045.10-4 M) and high doses of 4-ethylphenol (EC50 1,509.10-3 M) caused...
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The role of succinic acid in cardiac ischemic tolerance in rats
Kordač, Petr ; Neckář, Jan (advisor) ; Husková, Zuzana (referee)
Succinate is one of the intermediate in the Krebs cycle, which in recent years has been shown to interfere with other cellular events, some of which may affect cardiac ischemic tolerance. The aim of this project was to clarify its cardioprotective role in rat hearts subjected to acute ischemia-reperfusion. The myocardial resistance to acute ischemia (infarct size and incidence and severity of ischemic and reperfusion arrhythmias) was analyzed using the Langendorff method of isolated perfused heart at a constant flow with acute succinate administration. Local ischemia was induced by ligation of left anterior descending coronary artery. Acute administration of 1 mM succinate before 60 minutes of ischemia or before reperfusion only had a beneficial effect on reducing the infarct size by 25-30 % compared to the control group. At the same time, it had an adverse effect on the incidence and severity of ischemic and reperfusion arrhythmias. Key words: Succinate, heart, rat, heart-attack, ventricular arrhythmias
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The effect of morphine withdrawal on the catecholaminergic and serotonergic neurotransmitter system in rat brain
Nováková, Daniela ; Novotný, Jiří (advisor) ; Drastichová, Zdeňka (referee)
The aim of this diploma thesis is to study the effect of morphine withdrawal on catecholaminergic and serotonergic neurotransmitter system in rat brain. Theoretical part of this thesis summarizes basic information known about principles of neurotransmission with focus on the catecholaminergic and serotonergic system, metabolism of its components, their signaling, relevant receptors, their distribution, and especially their effect on morphine dependence and subsequent withdrawal. It also summarizes briefly principles of opioid signaling and outlines the findings yet known about neurochemical analysis of the transmitter systems mentioned above. Experimental part of this thesis is focused on the optimization of the method of high performance liquid chromatography with fluorescence detection and its subsequent use to determine basic components of catecholaminergic and serotonergic neurotransmitter system in samples of different part of brain of rats affected by intraperitoneal administration of morphine sulphate, and its subsequent withdrawal and correspondings unaffected control rats. The expression of selected catecholaminergic receptors in identical samples is also detected. This thesis succesfully implements gradient into the originally isocratic method of high performance liquid chromatography...
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