National Repository of Grey Literature 46 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Rat gut microbiome composition and metabolic faecal markers upon morphine withdrawal
Mičke, Bianka ; Novotný, Jiří (advisor) ; Pácha, Jiří (referee)
The primary purpose of this pilot study was a long-term monitoring of the gut microbiome composition and fecal markers of metabolism in rats following the completion of 10-day intraperitoneal administration of increasing morphine doses (from 10 to 50 mg/kg/day) and in the corresponding control groups of rats that didn't administrate morphine. This study involved the introduction of new methods for microbiome and metabolome research, statistical evaluation of results and interpretation of data, or hypothesis to explain the effects of morphine on the gut microbiome and fecal metabolome composition compared to the resulting data of similarly oriented studies. The actual experiment was conducted on male Wistar rats aged 2 months and weighing approximately 300 g, which were maintained on a standard chow diet. The analysis and evaluation of the resulting data showed that there were changes in the composition of the gut microbiome and fecal metabolome in the experimental group compared to the control group during the reporting period but the induced changes were rather temporary. Further studies should be performed using a significantly larger experimental and control group as well as higher time series granularity. Keywords: morphine, opioids, withdrawal, gut microbiome, faecal metabolome
Effect of stress on corticosteroid metabolism in peripheral tissues
Makal, Jakub ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
Stressor influence can lead to homeostatic disruption. To eliminate this threat, mechanism which compensates negative effects of stressor was evolved by organisms. It's called stress response. One of two major systems that moderate stress response of organism is hypothalamic- pituitary-adrenal axis (HPA axis). Effectors of the HPA axis are glucocorticoids, steroid hormones secreted from adrenal glands. Enzymes which metabolize glucocorticoids are located in target tissues for these hormones. They convert active glucocorticoids into their inactive forms, or vice versa. Untill now, two such enzymes have been described - 11beta-hydroxysteroid dehydrogenases type 1 and type 2. It was proved that expression and activity of these enzymes can change under the influence of stressor. These changes are tissue-specific and dependent on type of applied stressor.
Effect of stress on expression of glucocorticoid receptors and enzymes of glucocorticoid metabolism in specific structures of rat brain
Kvapilová, Pavlína ; Pácha, Jiří (advisor) ; Telenský, Petr (referee)
Stress response is trigerred by a number of factors, which, depending on the type of response they generate, involve different brain structures. These structures then relay the information to the paraventricular nucleus of hypothalamus (PVN), which is the main integration center for information about the imbalance of homeostasis induced by stressors. If it meets a sufficient number of excitatory signals, the PVN activates the hypothalamic pituitary adrenal axis, which ultimately triggers the secretion of stress hormones glucocorticoids, which then act back on the brain. This action is influenced by several factors, mainly the presence of local metabolism of glucocorticoids. Local metabolism is provided by the enzymes 11-hydroxysteroid dehydrogenases, which can locally activate or deactivate the hormone molecules and thus amplify or attenuate their effects.
Peripheral metabolism of glucocoricoids in immune cells
Ergang, Peter ; Pácha, Jiří (advisor) ; Kalous, Martin (referee) ; Teisinger, Jan (referee)
4 Abstract Glucocorticoids are hormones that regulate a variety of homeostatic processes including metabolism, cell proliferation, differentiation and immune functions, including inflammation. Acute inflammatory response is associated with an increase in glucocorticoid levels via the stimulation of pro-inflammatory cytokines and activation of the hypothalamo- pituitary-adrenal axis. Within target cells or tissues the glucocorticoid action depends not only on the plasma level of the hormone, its receptors and receptor-effector coupling, but also on the local metabolism of glucocorticoids. Two distinct types of this enzyme have been cloned and characterized. Type 1 (11HSD1) is a NADP+ (H)-dependent enzyme whose reductase activity predominates in intact cells. This enzyme activates cortisol and corticosterone from their 11-keto derivatives and thus increases the local concentration of active glucocorticoid. In contrast, type 2 (11HSD2) requires NAD+ as a co-substrate and possesses only dehydrogenase activity, thereby inactivating endogenous glucocorticoid hormones. We have demonstrated that inflammation (arthritis or experimental colitis) is accompanied by elevated 11-reductase activity and the expression of 11HSD1 mRNA, moreover in the case of colitis also with a decrease in the expression of 11HSD2....
Effect of stress on expression of 11β-hydroxysteroid dehydrogenase in rat brain
Kuželová, Andrea ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
This thesis examines the influence of stress on the activity of hippocampal CA1 area. The main task was to determine whether the stress load affects the changes of the local metabolism of glucocorticoids, and whether the levels of corticosteroid receptors in the CA1 hippocampus are modulated in response to stress. In order to answer these questions, the experiments were carried out using three different rat strains - Fisher, Lewis and Wistar which differ in their activities of hypothalamic-pituitary-adrenal axis. Our results demonstrate that stress has no effect on expression of MR mRNA. Conversely, stress reduces the levels of GR mRNA in CA1 area of the dorsal hippocampus. Moreover, we confirmed that the Lewis and Wistar rats didn't change metabolism of glucocorticoids after stress response. By the Fisher rats increased levels of 11β-HSD1 mRNA expression and therefore increased the metabolism of corticosterone.
Cholinergic regulation of ion transport in the large intestine
Hock, Miroslav ; Pácha, Jiří (advisor) ; Moravec, Jan (referee) ; Kolínská, Jiřina (referee)
anglicky Acetylcholine is one of the most important mediators of enteric nervous system involved in the regulation of ion transport in the large intestine. Although, recently, plenty of new evidences of various expression of ion transport proteins in distal and proximal colon was published, there still lacks an electrophysiological study comparing these parts of colon considering all that new findings. The aim of this study was thus to compare cholinergic regulation of ion transport in distal and proximal colon. We measured responses of distal and proximal colon in Ussing chambers by voltage-clamp method. The colonic epithelium was clamped to 0 mV and responses were recorded as changes of short-circuit current (SCC). Instead of acetylcholine we used its stable analogue carbachol. Data were processed and analyzed using a VBA code I wrote for this purpose for MS Excel 2007. We confirmed that carbachol acts directly on epithelial cells via muscarinic acetylcholine receptors in both, distal and proximal colon. These responses to carbachol were not influenced by inhibitors of Cl- channels situated in apical membrane (CFTRinh-172 and niflumic acid). Inhibition of basolateral influx of Cl- by serosal Ba2+ and furosemid reduced responses to carbachol in both, distal and proximal colon. Inhibitors of K+...
Analysis of the involvement of α2 - AMPK in the beneficial effects of n-3 polyunsaturated fatty acids on obesity - associated metabolic derangements
Jeleník, Tomáš ; Rossmeisl, Martin (advisor) ; Cahová, Monika (referee) ; Pácha, Jiří (referee)
It is well established that n-3 polyunsaturated fatty acids with long chain (n-3 LC-PUFA) have beneficial effects on the obesity-induced metabolic disorders in mice. However, in obese humans, the potency of these fatty acids to positively affect obesity and insulin resistance has been shown to be lower. The aim of the studies described in this thesis was to verify various approaches aimed at increasing efficiency of n-3 LC-PUFA and to study the involvement of 2 subunit of AMP-activated protein kinase (2-AMPK) in the mechanisms of action of these compounds. Firstly, various chemical derivatives of DHA were tested in mice. Substance-2, the -ethyl ester of DHA, completely prevented and even partially reversed the development of obesity, fat accumulation, impaired glucose tolerance, dyslipidemia and white adipose tissue inflammation, even though the dose was only 10 % of that normally used in mice for the treatment with n-3 LC-PUFA. Secondly, the combination of n-3 LC-PUFA and a low-dose of anti-diabetic rosiglitazone prevented, in additive manner, development of dyslipidemia and insulin resistance, reduced the accumulation of body fat and adipocyte hypertrophy, while inducing adiponectin in mice fed a high-fat diet. This treatment also reversed impaired glucose tolerance in obese mice. The major part...
Interactions between gut microorganisms and brain
Fajstová, Alena ; Pácha, Jiří (advisor) ; Hock, Miroslav (referee)
Intestinal microbiota communicates with brain via various cooperating pathways including neuronal, endocrine and immune. Pathogenic and commensal bacteria produce great amounts of neurotransmitters and various other metabolites which can interact with brain. Presence of bacteria can also induce immune system response which can influence brain through cytokines and other mediators. Last but not least the communication can be mediated through nerves, especially the vagus nerve. The brain can influence the intestines through sympathic and parasympathic efferent nerves and through hormones. Gut colonization by nonpathogenic commensal bacteria is crucial for proper brain development. If this doesn't happen in certain period psychiatric disorders such as depression or autism can occur later in life. Various pathological conditions might be ameliorated or fully reversed by administration of probiotic bacteria. Aim of this thesis is to briefly review factors influencing gut microbiota, its influence on the brain development and the role of probiotics in the therapy of intestinal and psychiatric diseases. Keywords: gut microbiome, brain, neuroendocrine regulation, probiotic, neurotransmitter

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