Submitted by Natalia Vieira (natalia.vieira@famerp.br) on 2016-05-19T21:52:28Z No. of bitstreams: 1 anacarolinadeabreu_dissert.pdf: 490120 bytes, checksum: 25e56f07305d458ef011d69e87061a78 (MD5) / Made available in DSpace on 2016-05-19T21:52:28Z (GMT). No. of bitstreams: 1 anacarolinadeabreu_dissert.pdf: 490120 bytes, checksum: 25e56f07305d458ef011d69e87061a78 (MD5) Previous issue date: 2015-12-14 / Since ancient times to nowadays, the Erectile Dysfunction has been considered a condition that has always affected men. It has been not only a reason for embarrassment, but also an issue of multifactorial cause related either to psychological or organic and drug factors. For this reason, a significant impact can be observed on the individuals quality of life and their partners while this is associated with low self-esteem, depression, difficult relationship and increased anxiety. As this issue is currently a bioethical matter, it is feasible and necessary to be solved. Its main focus is the principle of life protection; introduced into the Ethics of scientific progress and outlining the guiding and protective limits of the person. There is also the autonomy of the individual's will which has valued the man according to his own individuality as a human being with rationality and liberty. The majority of individuals are not well informed. They search also for easier or less embarrassing ways for treatment and solutions. As a result, it is up to them to choose, "searching for a skilled professional", or a searching for Websites, mysticisms and charlatan. Thus, this study by means of a search on databases such as Pubmed Index, Google and Google Scholar shows publications and data research approaching Erectile Dysfunction from 1930 to today. / Desde os tempos antigos até os dias de hoje, a Disfunção Erétil tem sido considerada uma condição que sempre afetou os homens. É não só um motivo para constrangimento, mas também uma questão de causa multifatorial e tem relação tanto a fatores, psicológicos, biológicos ou medicamentosos. Por esta razão, um impacto significativo pode ser observado na qualidade de vida dos indivíduos e suas parceiras e assim associada à diminuição da autoestima, depressão, difícil relacionamento e aumento da ansiedade. Como esta questão é atualmente de caráter bioético, torna-se oportuna e necessária para ser solucionada, esta nova ciência da vida. Seu foco principal é o princípio da proteção da vida; introduzido na ética do progresso científico e delineando os limites orientadores e protetores à pessoa. Há também a autonomia da vontade do indivíduo que tem valorizado cada um, segundo, a sua própria individualidade como um ser humano com racionalidade e a liberdade. A maioria dos indivíduos não está bem informada. Eles procuram formas mais fáceis ou menos embaraçosas para o tratamento e soluções. Como resultado, cabe-lhes escolher, “pela busca de um profissional capacitado", ou uma busca em sites, misticismos e popularismo. Assim, este estudo por meio de uma pesquisa em bases de dados indexadoras como Pubmed, Google e Google Scholar mostra publicações e dados de pesquisa sobre Disfunção Eréctil de 1930 até os dias atuais.

Cognitive impairment after stroke or transient ischemic attack (TIA) is a prototype of vascular cognitive impairment (VCI). 30% of subjects with poststroke cognitive impairment are detected Alzheimer’s disease (AD)-like amyloid-beta (Aβ) retention with reference to ¹¹C-Pittsburgh compound B (PiB) positron emission tomography (PET). Therefore, poststroke cognitive impairment provides a good clinical context for the study about contribution of comorbid Alzheimer’s and cerebrovascular disease (CVD) pathologies to cognition. In this thesis, there are four studies addressing the effect of Aβ on poststroke cognitive impairment. / The first study investigated the accuracy of diagnosing cognitive impairment subtype in subjects with stroke/TIA using current clinical diagnostic criteria with reference to ¹¹C-PiB PET. We found the agreement between the pre and the post-PET diagnoses was poor (Kappa=0.194). The overall accuracy of clinical diagnosis of pure VCI (pVCI) was 66.7%, while that of mixed (i.e., AD with CVD) VCI (mVCI) was 68.0%. / Dementia may occur after stroke/TIA within 3-6 months (early poststroke dementia [PSD]) or from 3-6 months onward (delayed PSD). In the second study, apart from age and history of diabetes mellitus, chronic small vessel disease (SVD) lesions including lacunes and white matter changes (WMC) predicted delayed PSD as they did for early PSD. With comparable levels of SVD, the presence of acute infarcts and AD-like Aβ retention were associated with the early dementia after stroke/ TIA. / So far, there is a lack of research on the long-term effect of Alzheimer’s pathology on cognitive impairment in the context of stroke/TIA. We hypothesized that comorbid AD-like Aβ deposition played a key role in progressive cognitive decline after stroke/TIA. To test this hypothesis, we conducted a 3-year longitudinal study as study 3. Over 3 years, there was significant difference between mVCI and pVCI on the changes of the Mini-Mental State Examination (MMSE) score over time. We observed a significant decline in MMSE in the mVCI group but not the pVCI group. The annual rates of decline in MMSE and Montreal Cognitive Assessment (MoCA) score were greater in the mVCI group compared to the pVCI group. Of all MoCA domains measured, memory, executive and visuospatial functions were related to Aβ deposition. / In study 4, we investigated the relative contribution of Aβ deposition and CVD lesions to neuropsychological profiles in subjects with cognitive impairment after stroke/TIA. We found that in mVCI, Aβ retention in deep region or parietal lobe was predominantly associated with memory or executive function, respectively. In pVCI, frontal WMC and global large acute infarcts could affect memory or executive function via brain atrophy. / The conclusion of these studies reported herein can be summarized as follows: First, the overall accuracy of clinical diagnosis for cognitive impairment subtypes after stroke/TIA was low. Second, subjects with AD-like Aβ deposition tended to have dementia early after stroke/TIA, and they were more likely to experience a continuous and more severe cognitive decline 3 years later. Finally, Aβ deposition could affect both memory and executive function directly as a predominant factor in subjects with mixed Alzheimer’s and CVD pathologies. / 中風或短暫性腦缺血發作後的認知障礙被普遍視為血管性認知障礙的一種原型。通過澱粉樣蛋白正電子發射計算機斷層掃描技術（¹¹C-PiB PET），30%的中風或短暫性腦缺血發作後認知障礙患者具有阿爾茲海默氏病型的澱粉樣蛋白(Aβ)沈積。因此，中風或短暫性腦缺血發作後認知障礙是一種研究共存的阿爾茲海默氏病和腦血管疾病對認知功能的影響的良好模型。該論文通過四個研究，闡述了Aβ對中風或短暫性腦缺血發作後認知功能的影響。 / 第一個研究通過藉助¹¹C-PiB PET,調查了臨床診斷中對中風或短暫性腦缺血發作後認知障礙的分型的準確性。我們發現，對不同認知障礙類型的臨床診斷準確率較低（Kappa=0.194）。其中，對血管性認知障礙的臨床診斷準確率為66.7％，對混合性(阿爾茲海默氏病和腦血管疾病混合型)認知障礙的臨床診斷準確率為68.0％。 / 通常，我們把於中風或短暫性腦缺血發作後3至6個月內發生的癡呆定義為早髮型中風或短暫性腦缺血發作後癡呆，3至6個月后發生的癡呆定義為晚髮型中風或短暫性腦缺血發作後癡呆。在第二個研究中，我們發現，慢性小血管病（腔隙性梗塞和腦白質病變）不僅可以導致早髮型中風或短暫性腦缺血發作後癡呆，而且和晚髮型中風或短暫性腦缺血發作後癡呆也有關聯。然而，如果在相同程度的小血管病損傷的情況下，具有急性缺血性損傷和阿爾茲海默氏型Aβ沈積的患者更易提早發生中風或短暫性腦缺血發作後癡呆。 / 迄今，尚無關於共存的阿爾茲海默氏病和腦血管疾病對認知功能的長期影響的研究。我們假設合併的阿爾茲海默氏病可以導致患者中風或短暫性腦缺血發作後認知功能持續下降。為了驗證這一假設，我們進行了一個為期3年的長期隨訪研究（研究三）。在三年的隨訪中，混合性認知障礙患者和血管性認知障礙患者的簡短認知檢測（MMSE）評分變化有著顯著不同：混合性認知障礙患者的MMSE評分顯著下降，而血管性認知障礙患者的MMSE評分則無明顯改變。而且，混合性認知障礙患者的MMSE和蒙特利爾認知評估量表（MoCA）評分每年下降的平均速度皆高於血管性認知障礙患者。此外，藉助MoCA，我們發現中風或短暫性腦缺血發作後認知障礙患者的記憶、執行能力和視覺空間能力的損傷都和Aβ沉積有關。 / 在第四個研究中，我們研究了Aβ和腦血管病損傷對中風或短暫性腦缺血發作後患者不同認知功能的影響。我們發現，在混合性認知障礙患者中，腦深部的Aβ沉積和記憶功能損害直接相關，腦頂葉的Aβ沉積則和執行功能損害直接相關。在血管性認知障礙患者中，額葉腦白質病變和全腦大型腦梗病灶則可通過腦萎縮的介導，影響記憶或執行功能。 / 總之，我們的研究發現: 1.目前關於中風或短暫性腦缺血發作後患者認知障礙分型的臨床診斷的準確性較低。2.具有阿爾茲海默氏型Aβ沉積的患者不僅易於在中風或短暫性腦缺血發作後早期發生認知障礙，而且其認知水平在長期隨訪中也會不斷下降。3. Aβ沉積可以作為主導因素直接影響混合性認知障礙患者的記憶和執行功能。 / Liu, Wenyan. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 164-187). / Abstracts also in Chinese; appendixes in Chinese. / Title from PDF title page (viewed on 12, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

1. Evaluate the mechanisms by which hyperglycemia and hypothyroidism occur in patients on certain targeted chemotherapy agents.2. Develop treatment recommendations for patients who develop these endocrine toxicities while on therapy.3. Establish appropriate monitoring guidelines for patient receiving certain targeted chemotherapy agents.

While cigarette smoking is a common-knowledge way to stay lean, it has long been known as a risk factor for diabetes and obesity. Here we establish that smoking causes fat gain and metabolic disruption in mice, effects which are exacerbated by a high-fat, high-sugar diet. We found that smoke exposure increases levels of ceramide—the lipid responsible for diet-induced insulin resistance—and that blocking ceramide production with the pharmacological inhibitor myriocin restored insulin sensitivity, stopped weight gain, and rescued mitochondrial respiration in vivo and in vitro.We also sought to assess the impact of the RAGE ligand HMGB1 on skeletal muscle metabolism. We found that respiration between vehicle and HMGB1-injected red gastrocnemius was comparable. In myotubes, adding myriocin treatment to the HMGB1 cells increased respiration above HMGB1 treatment alone. HMGB1 increased oxidative stress in cultured myotubes and increased the transcript levels of Spt2, the enzyme responsible for the rate-limiting step in ceramide synthesis, although transcript levels of markers of mitochondrial fission and fusion leave us unsure of HMGB1's impact on mitochondrial dynamics. HMGB1, even at an exceptionally low dose over only 2 weeks, did cause significant impairment in glucose and insulin tolerance tests. Considering HMGB1's accessibility as a therapeutic target, its involvement in metabolic disruption is worth pursuing further.

Vaskuläre Komplikationen wie Atherosklerose sind bei Diabetikern weit verbreitet. Eine erhöhte Produktion reaktiver Sauerstoffspezies trägt zu einer Dysfunktion des Endothels bei Diabetes und hohen Glukosespiegeln bei. Glutathion (GSH) ist das häufigste zelluläre Thiol und stellt ein bedeutendens Antioxidans des menschlichen Organismus dar. Das Multidrug Resistance Protein 1 (MRP 1) ist im Endothel der Haupttransporter von oxidiertem GSH. Blockiert man MRP 1, so wird unter oxidativem Stress der intrazelluläre GSH-Spiegel erhalten. In dieser Arbeit wird der Einfluss von MRP 1 auf die endotheliale Funktion und Produktion reaktiver Sauerstoffspezies bei Diabetes und erhöhten Glukosespiegeln anhand von MRP 1-/- -Mäusen und Wildtyp-FVB-Tieren untersucht. Acht Wochen nach Injektion von STZ wurde die endothelabhängige Vasorelaxation an den isolierten thorakalen Aorten bestimmt. Diabetische Wildtyp-Tiere wiesen eine signifikant verminderte endothelabhängige Vasorelaxation auf. In MRP 1-/- -Tieren hingegen kam es zu keiner Beeinträchtigung der Endothelfunktion. Die endothelunabhängige Vasorelaxation war nicht signifikant unterschiedlich. STZ-induzierter Diabetes führte zu einer signifikant erhöhten Produktion von Superoxidanionen sowie Wasserstoffperoxid in Wildtyp-Tieren. Diabetische MRP 1-/- -Mäuse hingegen zeigten keinen Anstieg der Produktion reaktiver Sauerstoffspezies. Erhöhte Glukosekonzentrationen führten in vitro in humanen aortalen Endothelzellen ebenso zur erhöhten Superoxidanion-Produktion. In Zellen, in denen MRP 1 mittels siRNA herunterreguliert war, zeigte sich keine Erhöhung von Superoxidanionen. In Wildtyp-Mäusen führte Diabetes zu einer Verminderung des vaskulären GSH-Spiegels, wohingegen bei MRP 1-/- -Tieren keine Veränderung auftrat. Diese Daten weisen auf die wichtige Rolle von MRP 1 bei der unter hohen Glukosekonzentrationen auftretenden endothelialen Dysfunktion hin. MRP 1 stellt somit einen neuen Ansatzpunkt in der Behandlung der durch Diabetes ausgelösten vaskulären Dysfunktion dar. / Vascular complications and atherosclerosis are common in patients with diabetes. An increased production of reactive oxygen species contributes to endothelial dysfunction in diabetes. A major cellular defense against reactive oxygen species is Glutathione. The multidrug resistance associated protein 1 is the main transporter of oxidized glutathione in endothelial cells. Blockade of MRP 1 prevents endothelial cell dysfunction induced by reactive oxygen species. Diabetes was induced in 12 week old male MRP 1-/- mice or corresponding FVB background wildtype mice by injection of streptozotocin. Eight weeks thereafter endothelium-dependent vasorelaxation was blunted in isolated thoracic aortae. In aortae from diabetic mice lacking MRP 1, endothelium-dependent vasorelaxation was only mildly impaired. STZ induced diabetes increased aortic superoxide and hydrogen peroxide production in wildtype animals, while in aortae from MRP 1-/- mice the reactive oxygen species production was nearly unchanged by diabetic conditions. Aortic levels of reduced glutathione were diminished in diabetic FVB. Glutathione levels did not change in diabetic MRP 1-/- mice. These data indicate that MRP 1 plays an important role for endothelial dysfunction and reactive oxygen species production in diabetes and under conditions of high glucose. MRP 1 therefore may represent a therapeutic target in treatment of diabetes induced vascular dysfunction.

Where is the importance in uncovering a link between the economic position and level of familial dysfunction in the short stories of Ernest Hemingway and F. Scott Fitzgerald? Furthermore, in composing these findings, what does this information have to offer in terms of bringing different insights to the works of these two writers who have already received so much attention from critics? In reading and researching the short stories of Hemingway and Fitzgerald, I find that published criticism has not sufficiently examined the connection between economic position and familial dysfunction. Trying to understand the psychology behind the characters’ lives and their consequential actions, however, requires us to look at this connection. One can articulate the effects and results that economic circumstances have in relation to the characters’ familial duties and responsibilities. / Thesis / Master

The aim of this study was to make an assessment of the role of the cognitive component in the development of sexual dysfunction. Past studies have largely focused on the impact of particular events on sexual dysfunction and have not assessed the role of the perception of these events. A number of theories on sexual dysfunction have been developed to explain the influence of cognitions, but these have not been empirically tested. This study investigated the role of the cognitive evaluation of sexual experiences among 30 sexually dysfunctional participants and 30 control participants who were matched on age, marital status and biological sex. The Cognitive Aspects of Sexual Dysfunction Measure (CASDM) was constructed to evaluate sexual dysfunction. This measure was designed to tap into the major events in participants’ lives and, more importantly, the participants’ perceptions of these events. The components assessed were the intergenerational (family of origin), individual, current life and relationship aspects of the person’s life. These factors were measured from the responses to questions regarding the participant's cognitions about past experiences, the effect of the past experience on the participant at the lime it occurred and the influence this experience had on the participant's sense of self now, their relationship now and sexual functioning now. The main findings in the intergenerational area were that past experiences were perceived by the sexually dysfunctional group to be having an impact on the self, relationships and their sexual functioning although there were no actual differences between the sexually functional and the sexual dysfunctional participants in the occurrence of the event. For the individual factors, there were differences between the sexually functional and sexually dysfunctional participants in both values and lifestyle, although these were not perceived to be having an impact on the self, relationship and sexual functioning. In the relationship area, anger was the major factor separating the sexually functional and sexually dysfunctional groups. Anger was high among the sexually dysfunctional participants and was perceived to be having an impact on self, the couple’s relationship and their sexual functioning. The importance of all these variables in providing a better understanding of the cognitive factors in sexual dysfunction was discussed. The findings demonstrate the importance of cognitions in influencing sexual functioning. Clinicians should not simply deal with the life experiences of sexually dysfunctional people when attempting to change their behaviour, but should focus on changing cognitions about the behaviours in relation to sexual functioning.

Purpose: The relationship between severity of voiding dysfunction and quality of life in children with daytime wetting was analyzed. Materials and Methods: The relationship between age, gender, severity of voiding dysfunction (measured by DVSS) and quality of life (measured by PinQ) in the child with daytime wetting was analyzed. Twenty-four children (4 males, 20 females) aged 5-10 years (x 8.17 years, SD 1.37) and their parents completed the DVSS and PinQ. Results: Parent and child total DVSS and total PinQ Scores had similar results with only a significant mean difference between the parent total DVSS scores based on gender. Only Gender with Parental Total DVSS Score (r = 0.462, p = 0.023) and Child Total DVSS Score with Parent Total DVSS Scores (r = 0.472, p = 0.020) were significant correlations. Conclusions: Results illustrate the importance of early recognition and intervention to minimize the impact daytime wetting has on the child.

Research on aging indicates that older adults do not, as a group, report decreased health-related quality of life (HRQOL) despite age-related declines in physical health status. Several cognitive adaptation strategies have been suggested to underlie HRQOL stability in this population. Studies of older cancer patients nevertheless show substantial variance in post-treatment HRQOL outcomes, although cognitive mechanisms for individual differences have received little attention. The current study expanded on a developmental adaptation of self-regulation theory in which aging influences both self-vulnerability and perceptions of disease. A model was tested in which older age was hypothesized to predict better HRQOL via less severe illness perceptions in men treated for localized (Stage I and II) PC. Results indicated that age was not directly associated with HRQOL. However, older age was indirectly associated with better HRQOL via less severe PC perceptions. Further, this indirection association helped account for the positive association between age and HRQOL that three risk factors (income, comorbid disease burden, and sexual function) were shown to suppress. Perceptions of PC may promote HRQOL stability by mitigating age-related declines in health and income status. Disease perceptions thus represent critical components of health assessments and interventions for PC survivors of all ages, but particularly for men facing difficulties adapting to complex health profiles or normative lifespan challenges.

The number of people having diabetes mellitus is increasing worldwide at an alarming rate. An unbalanced diet rich in carbohydrates and saturated fats, obesity and lack of physical activity, are being blamed. The worldwide prevalence of diabetes for all age-groups has been estimated to be 2.8% in 2000 and projected to be 4.4% by the year 2030. The pathogenesis of diabetes, especially the recent epidemic increase in type 2 diabetes, is still far from clear. Endothelial dysfunction, commonly defined as reduced endothelium-dependent relaxation due to reduced availability of the vasodilator mediator nitric oxide (NO), is a hallmark of diabetes mellitus. Methylglyoxal (MG) is a highly reactive dicarbonyl compound mainly formed as an intermediate during glycolysis. MG is also formed to a lesser extent from protein and amino acid metabolism. However, the relative contribution of various metabolic precursors to MG formation is not known. Levels of MG have been found to be elevated in diabetic and hypertensive conditions but it is not known whether MG is the cause or the effect of these pathological conditions. The aim of my project was (i) to quantify the amount of MG and oxidative stress produced from various substrates in cultured A10 vascular smooth muscle cells (VSMCs), (ii) to investigate the acute in vivo effects of a single dose of MG on glucose tolerance in male Sprague-Dawley (SD) rats, (iii) to investigate the effects of MG on endothelial function and (iv) to investigate the effects, and the underlying molecular mechanisms, of chronic administration of MG on glucose homeostasis in male SD rats. The results show that aminoacetone, a protein metabolism intermediate, is the most potent substrate for MG formation on a molar basis, whereas D-glucose and fructose are equipotent. I also established optimum sample preparation protocols for reproducible measurement of MG in biological samples by high performance liquid chromatography (HPLC). In normal SD rats a single acute dose of MG induced glucose intolerance, reduced adipose tissue glucose uptake and impaired the insulin signalling pathway, which was prevented by the MG scavenger and advanced glycation end product (AGE) breaking compound, alagebrium (ALT-711). MG and high glucose (25 mM) induced endothelial dysfunction in rat aortic rings and cultured endothelial cells by reducing endothelial nitric oxide synthase (eNOS) phosphorylation at Ser-1177, activity and NO production. MG and high glucose also increased oxidative stress and further reduced NO availability in rat aortic rings and cultured endothelial cells. Chronic administration of MG in normal SD rats by continuous infusion with a subcutaneously implanted minipump for 28 days (60 mg/kg/day), induced metabolic and biochemical abnormalities of glucose homeostasis and insulin regulation that are characteristic of type II diabetes. In MG treated rats, insulin stimulated glucose uptake in adipose tissue, and glucose stimulated insulin release from freshly isolated pancreas, were significantly reduced as compared to saline treated control rats. At a molecular level, insulin gene transcription was significantly impaired and apoptosis and DNA fragmentation were more prevalent in the pancreas of MG treated rats as compared to untreated control rats. All of these in vivo effects of MG were attenuated by the MG scavenger, alagebrium. Our data strongly indicate that MG is a causative factor in the pathogenesis of endothelial dysfunction and type 2 diabetes mellitus.