It is well established that low level Pb-exposure is associated with a wide range of cognitive and neurobehavioral dysfunctions in children. In fact, Pb-induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum - the anatomical sites which are crucial in modulating emotional response, memory and learning. Previously it was also shown that nitric oxide (NO) signaling pathway as well as glutamatergic neurotransmission are both involved in brain development, neurotoxicity and neurodegeneration processes whereas Pb2+ interfere with both. For this reason we investigated the effect of ontogenetic Pb2+ exposure on dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) of rats after amphetamine (AMPH) and/or 7-nitroindazole (7-NI) administration. Furthermore, the possible role of oxidative stress in Pb2+-induced neurotoxicity in prenatally Pb2+-treated rats was explored in the content of hydroxyl radical (HO•) species in mPFC after AMPH and/or 7-NI injection, assessed by HPLC analysis of 2.3-dihydroxybenzoic acid (2.3-DHBA) - spin trap product of salicylate. As shown, the results of this study suggest that Pb2+ exposure during intrauterine life did not substantially affect cortical dopaminergic neurotransmission in adult offspring rats evaluated by means of microdialysis of mPFC and the content of the cortical HO•. It is likely that striatum, nucleus accumbens or other dopamine rich brain areas are more intricately associated with Pb2+ precipitated behavioral, dopamine - dependent impairments observed in mammalians.

In the present study, we examined the possible effect of chronic treatment with glucocorticoids on the morphology of the rat brain and levels of endogenous agmatine and arginine decarboxylase (ADC) protein, the enzyme essential for agmatine synthesis. Seven-day treatment with dexamethasone, at a dose (10 and 50 μg/kg/day) associated to stress effects contributed by glucocorticoids, did not result in obvious morphologic changes in the medial prefrontal cortex and hippocampus, as measured by immunocytochemical staining with β-tubulin III. However, 21-day treatment (50 μg/kg/day) produced noticeable structural changes such as the diminution and disarrangement of dendrites and neurons in these areas. Simultaneous treatment with agmatine (50 mg/kg/day) prevented these morphological changes. Further measurement with HPLC showed that endogenous agmatine levels in the prefrontal cortex and hippocampus were significantly increased after 7-day treatments with dexamethasone in a dose-dependent manner. On the contrary, 21-day treatment with glucocorticoids robustly reduced agmatine levels in these regions. The treatment-caused biphasic alterations of endogenous agmatine levels were also seen in the striatum and hypothalamus. Interestingly, treatment with glucocorticoids resulted in a similar change of ADC protein levels in most brain areas to endogenous agmatine levels: an increase after 7-day treatment versus a reduction after 21-day treatment. These results demonstrated that agmatine has neuroprotective effects against structural alterations caused by glucocorticoids in vivo. The parallel alterations in the endogenous agmatine levels and ADC expression in the brain after treatment with glucocorticoids indicate the possible regulatory effect of these stress hormones on the synthesis and metabolism of agmatine in vivo.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12919号 / 論医博第2094号 / 新制||医||1009(附属図書館) / 32129 / (主査)教授 戸口田 淳也, 教授 妻木 範行, 教授 安達 泰治 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19568号 / 医博第4075号 / 新制||医||1013(附属図書館) / 32604 / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊佐 正, 教授 渡邉 大, 教授 影山 龍一郎 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第20813号 / 人健博第50号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 三谷 章, 教授 二木 淑子, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DGAM

京都大学 / 0048 / 新制・論文博士 / 博士(人間健康科学) / 乙第13171号 / 論人健博第5号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 十一 元三, 教授 木下 彩栄, 教授 伊佐 正 / 学位規則第4条第2項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第21422号 / 人健博第63号 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 稲富 宏之, 教授 澤本 伸克, 教授 伊佐 正 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21674号 / 医博第4480号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 安達 泰治, 教授 黒田 知宏, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The aim of this diploma thesis is to analyze the media construct of the European Union in chosen Czech mediae. The work applies to a concrete section of medial world using the method of discourse analysis and describes the structural means of the medial image of the European Union, emphasizing the ideological and political aspect of the analyzed material. The analysis is based on the certain period of 2018, when the presidential elections took place. This period was chosen due to the higher probability of occurrence of the required material. The material for discourse analysis was selected in the weekly magazines Echo and Respekt. The crucial criterion for the selection of these two periodicals was their explicit orientation towards conservative, alternatively liberal ideological orientation. The work describes the variability of the creation of media constructs. Due to the wide range of linguistic means, that can be used in discourse analysis, it was necessary to concretize the analysis into several partial linguistic phenomenons. The work is mainly structured in a form of metaphor due to the frequency and the influence. In the analysis, it was necessary to proceed to a more detailed categorization of metaphor so that it could be applied to specific textual material. At the same time, the most...

Every 37 seconds, someone in the United States dies from cardiovascular disease. Vascular calcification is one of the underlying causes of these fatal events. Medial calcification develops following arteriosclerosis, or hardening of the arteries. Medial calcification is characterized by the deposition of hydroxyapatite in the medial layer of the arteries after normal vascular smooth muscle cells undergo a phenotypic switch to resemble osteoblast-like cells. It is hypothesized that this switch is caused by the wingless related (WNT)-Signaling pathway. The WNT-Signaling pathway, upon activation, causes the upregulation of osteogenic markers for the development of osteoblast-like cells. Current treatments alleviate consequences of calcification but do not address the disease. Due to a lack of cures for calcification, a novel therapy for this disease is overdue. By studying human aortic smooth muscle cells and confirming the role of WNT-Signaling as it relates to calcification, a possible therapeutic target for calcification can be identified.