A Doença de Alzheimer é uma doença neurodegenerativa progressiva e de início tardio, que compromete principalmente as areas da cognição, julgamento e estabilidade emocional. Esta doença se caracteriza por dois tipos de lesões cerebrais características: emaranhados neurofibrilares e placas senis. Os emaranhados neurofibrilares são compostos por uma proteína do citoesqueleto (proteína tau) hiperfosforilada e agregada. As placas senis são formadas por agregados da proteína β-amilóide. A doença de Alzheimer é resultado dainteração de vários fatores ainda incompletamente elucidados; não obstante, o estresse oxidativo e os processos inflamatórios ocupam posição de destaque dentre esses fatores. Neste trabalho, avaliamos as atividades das enzimas eritrocitárias superóxido dismutase, catalase e glutationa peroxidase, assim como o conteúdo plasmático de glutationa total, vitamina C, α-tocoferol, β-caroteno, licopeno e coenzima Q10. A esses parâmetros antioxidantes foram contrapostas medidas de oxidação de lipídios e proteínas plasmáticas. Adicionalmente, efetuamos a avaliação das expressões monocitárias de HLADR e CD-11b, e das citocinas IL-6, IL-1α e TNF-α. Nossos resultados mostram que os pacientes de doença de Alzheimer possuem níveis circulantes de atocoferol inferiores aos pacientes controles, e possuem monócitos que apresentam maior expressão basal de HLA-DR e maior produção de IL-1α quando estimulados por LPS. Esses resultados fortalecem a hipótese inflamatória na doença de Alzheimer, de acordo com trabalhos recentes que apontam bons resultados com o a-tocoferol na sua prevenção e tratamento. / Alzheimer\'s disease is a late-onset, progressive degenerative disease that affects mainly the judgement, emotional stability and memory domains. This disease is characterized by two telltale cerebral lesions: neurofibrillary tangles and senile plaques. Neurofibrillary tangles are constituted by hyperphosphorylated cytoskeleton protein tau aggregates, while senile plaques are mainly composed by β-amyloid protein aggregates. Alzheimer\'s disease is the outcome of a complex interaction among several factors which are not fully understood yet; nevertheless it is clear thar oxidative stress and inflammatory pathways rate high among these factors. In this work, we evaluated the erythrocytic acitivities of superoxide dismutase, catalase and glutathione peroxidase, as well as the plasma levels of total glutathione, α-tocopherol, α-carotene, lycopene, and coenzyme Q10. These antioxidant parameters were confronted with plasmatic levels of protein and lipid oxidation products. Additionally, we measured the basal expression of monocyte HLA-DR and CD-11b, as well as the monocyte production of the cytokines IL1-α, IL-6 and TNF-α. Our results show that Alzheimer\'s Disease patients show lower plasmatic levels of α-tocopherol when compared to control patients, and have higher basal monocyte HLA-DR expression associated with higher IL-1α production when stimulated by LPS. These results lend support to the inflammatory theory of Alzheimer\'s disease, according to recent works that indicate good results of α-tocopherol administration in both its prevention and treatment.

Dissertation (Ph.D.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 98 pages. Includes vita. Includes bibliographical references.

Introdução: A formação de atelectasia durante a indução anestésica pode ser um dos fatores responsáveis pela ocorrência de complicações pulmonares pós-operatórias (CPP). A aplicação de pressão positiva expiratória ao final da expiração (PEEP), uso criterioso de altas frações inspiradas de oxigênio e a utilização de manobras de recrutamento alveolar no período intra-operatório são recursos utilizados para a prevenção de atelectasia em procedimentos anestésicos. O objetivo deste estudo foi avaliar o modelo de ventilação mecânica adotado em procedimentos anestésicos de longa duração e suas correlações com as complicações pulmonares pós-operatórias. Métodos: Foram avaliadas em estudo observacional as cirurgias com mais de cinco horas de duração. No início do procedimento anestésico, na sala de cirurgia e após o seu término, na unidade de terapia intensiva, os parâmetros ventilatórios utilizados foram anotados e correlacionados com os achados das radiografias torácicas e saturação periférica de oxigênio (SpO2) em ar ambiente. Resultados: Cento e vinte e um pacientes foram observados. O tempo total de anestesia 499,4 ± 159,8 minutos. O volume corrente (VC) determinado no período intraoperatório foi 8,09 ± 2,15 mL/kg e a PEEP utilizada de 3,05 ± 2,31 cmH2O. Houve diferença para a mediana da SpO2 em ar ambiente (96% [95-97] vs 95% [92-96], p <0,001) comparando os períodos pré e pós-operatório. A freqüência de pacientes que apresentaram atelectasia nas radiografias de tórax do período pós-operatório (38,8%) foi significantemente maior que a do período pré-operatório (0%), x2=32,259. Não foi encontrado correlação entre os achados e o tempo de anestesia (p=0,708); a PEEP intra-operatória (p=0,296); tempo de permanência com suporte ventilatório mecânico no pósoperatório (p = 0,146) e tabagismo (p = 0,563). Conclusões: No período intra-operatório o PEEP utilizado em procedimentos de longa duração é baixo. Ocorre queda na SpO2 e aumento na incidência de atelectasia no período pós-operatório em comparação com o pré-operatório. São necessários outros estudos para melhor avaliação dos fatores responsáveis / Introduction: The formation of the atelectasis during the induction of the anesthesia can be one of the factors involved in the occurrence of postoperative pulmonary complications (PPCs). The application of the positive end-expiratory pressure (PEEP), low inpiratory concentrations of oxygen and the alveolar recruitment maneuvers perform in the intraoperative period are approaches used in the prevention of atelectasis in the anesthesia procedures. The objective of this study was to evaluate, in prospective observational study, the pattern of mechanical ventilatory assistence during longer anesthesia procedures and its correlations with the PPCs. Methods: The surgeries procedures longer than five hours have been evaluated in observational study. At the beginning of the anesthesia procedure, in the operatory room and after its terminus, in the intensive care unit, the mechanical ventilation parameters were determined and correlated with the findings in the chest x-rays and peripheral oxygen saturation (SpO2) in room air. Results: One hundred twenty one patients have been observed. The total time of anesthesia was 499,4 ± 159,8 minutes. The tidal volume (VT) in the intraoperative period was 8,09 ± 2,15 mL/kg and the PEEP used was 3,05 ± 2,31 cmH2O. There was a difference for the median of the SpO2 in room air (96% [95-97] vs 95% [92-96], p <0,001) comparing the pre and postoperative periods. The frequency of patients who had presented atelectasis in the chest x-rays of the postoperative period (38,8%) was significantly higher than the preoperative period (0%), x2=32,259. No correlation was found among these findings and the anesthesia time (p=0,708); the intraoperative PEEP used (p=0,296); time with mechanical ventilatory support in the postoperative period (p = 0,146) and smoking habits (p = 0,563). Conclusions: In the intraoperative period, the PEEP is low in longer procedures. The SpO2 decreases and the incidence of the atelectasis increases in the postoperative period, when compared with the preoperative one. Other researches are required for better evaluation of the factors related for the development of the PPCs

A metionina sintase redutase (MTRR) catalisa a redução da cobalamina (Cbl) oxidada a metilcobalamina. Em presença de folato, a metionina sintase (MTR) utiliza a metilcobalamina como cofator na metilação da homocisteína (tHcy) a metionina. O objetivo deste estudo foi avaliar os efeitos dos polimorfismos MTR A2756G e MTRR A66G nas concentrações dos metabólitos marcadores de deficiência de Cbl e folato em gestantes e neonatos. Os genótipos dos polimorfismos MTR A2756G e MTRR A66G foram obtidos por PCR-RFLP. O genótipo MTR 2756AA foi relacionado aos maiores valores de tHcy em gestantes e MMA em neonatos. Gestantes com genótipos MTRR 66AG e GG e com menores concentrações de Cbl apresentaram maior risco de apresentar concentrações elevadas de tHcy. Neonatos com genótipos com MTRR 66AG e GG apresentaram menores valores de SAM. Os polimorfismos MTR A2756G e MTRR A66G interferem nas reações dependentes de Cbl e folato em gestantes e neonatos. / Methionine synthase reductase (MTRR) catalyzes the reductive reaction of oxidized cobalamin to methylcobalamin. When folate is present, methionine synthase (MTR) uses methylcobalamin cofactor at homocysteine to methionine methylation process. The aim of this study was to evaluate the effects of MTR A2756G and MTRR A66G polymorphisms on total homocysteine (tHcy), methylmalonic acid (MMA), S-adenosylmethionine (SAM) concentrations and SAM/SAH ratio in Brazilian pregnant women and their newborns. Genotypes of two polymorphisms were determined by PCR-RFLP. MTR 2756AA genotype was associated with higher tHcy and MMA levels in mothers and babies, respectivelly. Lower cobalamin concentrations associated with MTRR 66AG and GG genotypes increased risk to elevated tHcy levels in pregnant women. The SAM levels were lower in neonates with MTRR 66AG e GG genotypes. The polymorphisms MTR A2756G and MTRR A66G could affect cobalamin and folate dependent reactions in pregnant women and newborns.

An analysis of air quality data from British Columbia has identified the Lower Mainland and surrounding rural areas as one of the regions in Canada where the Canadian Maximum Acceptable Air Quality Objective of 0.082 ppm ozone for one hour is frequently exceeded. Ozone at this level has the potential for affecting crops in the Fraser Valley. Field experiments were undertaken to attempt to evaluate the effect of randomly fluctuating levels of ozone on the yield of two cultivars each of Brassica oleracea L. (broccoli), Phaseolus vulgaris L. (bean), Pisum sativum L. (pea), Daucus carota L. (carrot) in 1985 and on one cultivar each of Solanum tuberosum L. (potato) and Pisum sativum L. (pea) in 1986, using a zonal air pollution system. As there is no current consensus regarding the most appropriate numerical expression of pollutant exposure to use in vegetation response studies, a comparison of various exposure terms was also undertaken. Ozone was added in various proportions to ambient levels between 0700 and 2100 hours (PDT) throughout the growing season. Three levels of ozone addition were used in 1985 and 12 in 1986. In 1985, treatments were assigned to three blocks over which ozone was released. Each block was supplied with different total amounts of supplementary ozone, a fourth block serving as an ambient air control. In 1986, ozone treatments were randomly assigned to four sub-plots on each of the three blocks over which ozone was released, with each block receiving the same total amount of supplementary ozone. Different treatments were achieved by each sub-plot being subject to different rates of release and degrees of mixing. For both years the ozone concentration distributions achieved over the season were approximately log-normal. Additional analysis of the air quality data from the ambient air plot found other types of skewed distributions such as the three parameter Weibull, three parameter gamma and Johnsons SB (four parameter log-normal) provided better descriptions of the data. The distribution providing the best fit depended on the concentration averaging time, the daily time span over which the ozone concentrations are analyzed and the selection criterion used. In 1985, field observations indicated that there were numerous plot to plot differences for disease and soil factors, which were confounded with the ozone treatments applied. Without true replication of the treatments, differentiation between the effects due to ozone and those from abiotic and biotic causes was not possible, and hence no clear conclusions concerning ozone response could be drawn. In 1986, without the confounding of ozone and plot location, significant linear reductions in yield were found for pea and pod fresh weight using the number of days on which the concentration exceeded 25 ppb, during the vegetative growing period (D25²). A significant linear reduction in fresh potato tuber weight was found using the geometric mean of all geometric mean ozone concentrations computed between 1200 and 1259-h for the season (GH12) as the exposure statistic. A significant multiple linear regression was found for pea fresh weight using the D25¹, statistic together with the number of occurrences in which the concentration exceeded 25 ppb for two, three and four consecutive hours (2C25, 3C25 and 4C25 respectively) in an episode; and for pod fresh weight using D25, 2C25 and 3C25 as independent variates. From the results presented it seems clear that ozone at the concentrations dispensed here would have a significant negative impact on crops grown in the Fraser Valley. Based on the 1986 experiment the best case estimate indicates that yield reductions of 28% could be expected for peas and potatoes at 37 ppb ozone (expressed as the season-long 7-h mean, M7). The exposure statistics used in the present study in comparison with the season-long 7 and 12 hour means provided good fits with the data. They are easily calculated from ambient air quality data and present attractive alternatives to those exposure statistics currently in use, for assessing the potential impact of ozone on crops in the Fraser Valley and for use in the setting of air quality standards. / Land and Food Systems, Faculty of / Graduate

Indiana University-Purdue University Indianapolis (IUPUI) / Endodontic regeneration treatment of necrotic immature teeth has gained popularity in recent years. The approach suggests a biological alternative to induce a continuous root development. In this project, three in vitro experiments were conducted to investigate the effect of three medicaments used in endodontic regeneration on mechanical properties and chemical structure of radicular dentin. In the first experiment, we investigated longitudinally the effect of medicaments on the indentation properties of the root canal surface of immature teeth using a novel BioDent reference point indenter. A significant difference in the majority of indentation parameters between all groups was found after one-week and one-month application of medicaments (p<0.0001): triple antibiotic paste (TAP) > double antibiotic paste (DAP) > control > calcium hydroxide [Ca(OH)2]. The four-week exposure of dentin to TAP and DAP caused 43% and 31% increase in total indentation distance outcome, respectively. In the second experiment, we investigated longitudinally the effect of medicaments on the chemical structure of immature radicular dentin by measuring the phosphate/amide I ratios of dentin using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy. Phosphate/amide I ratios were significantly different between the four groups after one week, two weeks and four week application of medicaments (p<0.0001): Ca(OH)2-treated dentin > untreated dentin > DAP-treated dentin > TAP-treated dentin. In the third experiment, we investigated longitudinally the effect of medicaments on root fracture resistance and microhardness of radicular dentin. For the microhardness, the two-way interaction between group and time was significant (p<0.001). TAP and DAP caused a significant and continuous decrease in dentin microhardness after one and three month application, respectively. The three-month intracanal application of Ca(OH)2 significantly increased the microhardness of root dentin. The time factor had a significant effect on fracture resistance (p<0.001). All medicaments caused significant decrease in fracture resistance ranging between 19%-30% after three month application compared to one week application. The three medicaments used in endodontic regeneration caused significant change in the chemical integrity of the superficial radicular dentin and significantly affected the indentation properties of the root canal surface. Furthermore, the three month intracanal application of medicaments significantly reduced the fracture resistance of roots.

Indiana University-Purdue University Indianapolis (IUPUI) / Tobacco smoking is considered a major modifiable risk factor for periodontal disease. Tobacco contains about 6700 compounds and almost 4000 compounds of these have been identified in tobacco smoke. Nicotine is the addictive ingredient in tobacco and has been shown to affect multiple cellular processes. Cigarette smoke condensate (CSC) is the particulate matter of smoke. It is believed to be a powerful inducer of inflammatory responses. Neutrophils are the first line of host defense and are critical cells in the maintenance of periodontal health through their role in the control of bacteria, but they can also contribute to the progression of periodontal disease by the production and release of reactive oxygen species (ROS). Virulence factors from periodontal pathogens, such as Porphyromonas gingivalis (P. gingivalis), stimulate the respiratory burst of neutrophils. In this dissertation, three studies aimed at understanding the oxidative activity of neutrophils when stimulated with either nicotine, cigarette smoke condensate (CSC) or four other components of tobacco smoke (2-naphthylamine, hydroquinone, acrolein, and acetaldehyde) with or without P. gingivalis supernatant. The release of matrix metalloproteinase-9 (MMP-9) was also examined. ROS production increased significantly when the neutrophils were stimulated with nicotine. P. gingivalis induced the maximum ROS production when compared to all the other components examined. The combination of nicotine and P. gingivalis did not have an additive effect on ROS production. Nicotine significantly increased the MMP-9 release from the neutrophils. On the contrary, CSC inhibited ROS production at all the concentrations examined. The combination of CSC and P. gingivalis resulted in the inhibition of ROS production. MMP-9 release was also increased from the CSC-treated neutrophils. The four other tobacco smoke components examined affected ROS production and MMP-9 release differently. These projects demonstrated that CSC inhibited the ROS production from neutrophils, which can be attributed to several components in tobacco smoke that may include acrolein and hydroquinone. More research is needed to determine the mechanisms of inhibition and if other tobacco components are involved in ROS inhibition

BACKGROUND: Current guidelines give class I recommendations for uninterrupted use of dabigatran rivaroxaban as an alternative to vitamin K antagonist (VKA) in patients of atrial fibrillation (AF) who are undergoing catheter ablation. The recent randomized controlled trials have shown similar efficacy of novel oral anticoagulants when compared to VKA in these patients. We sought to perform a meta-analysis with a focus on subgroup analysis of novel oral anticoagulants. METHODS: We searched PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through August 2020. Six RCTs studies (n = 2260) comparing the use of NOACs versus VKA in patients with AF undergoing catheter ablation were included. The odds ratio (OR) with 95% confidence interval was computed and P < 0.05 was considered as a level of significance. Major adverse cardiac events (MACE) were considered as a primary endpoint. RESULTS: Our results showed a significant difference in MACE between NOACs and VKA [OR 0.57 (0.37-0.88); P = 0.01] and in major bleeding events [OR 0.55 (0.35-0.86); P = 0.009], which is mainly derived from the use of dabigatran. No significant difference in MACE or major bleeding events was found on the subgroup analysis of rivaroxaban and apixaban over VKA therapy. CONCLUSION: Uninterrupted use of NOACs is safe and effective alternative for the prevention of cerebral thromboembolism and reducing the risk of major bleeding in patients undergoing catheter ablation of AF. However, the individual subgroup analysis showed that only dabigatran is superior to VKA in terms of reducing MACE through a reduction in major bleeding. The rivaroxaban, apixaban and edoxaban are non-inferior to VKA therapy based on these results. Further studies are needed to generalize these recommendations in morbidly obese patients.

Objectives: Adherence to psychotropic medication is poor among individuals with bipolar disorder (BD). To understand treatment experiences and associated adherence among these individuals, we developed a novel construct of Clinical Net Benefit (CNB) using psychiatric symptoms, adverse effects and overall functioning assessments. We tested whether adherence differed across classes of CNB, whether individuals transitioned between classes over time, and whether these transitions were differentially associated with adherence. Methods: Data come from individuals aged 18+ during five years of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Latent class analysis identified groups of CNB. Latent transition analysis determined probabilities of transitioning between classes over time. Adherence was defined as taking 75%+ of medications as prescribed. Associations between CNB and adherence were tested using multiple logistic regression adjusting for sociodemographic characteristics. Results: Five classes of CNB were identified during the first two years (high, moderately high, moderate, moderately low, low), and four classes (removing moderately high) during the last three years. Adherence did not differ across classes or time points. Medication regimens differed by class; those with higher CNB taking fewer medications had lower odds of adherence while those with lower CNB taking more medications had higher odds of adherence compared with monotherapy. Probability of transitioning from higher to lower CNB, and lower to higher CNB was greatest over time. Conclusions: CNB is heterogeneous in individuals treated for BD, and movement between classes is not uncommon. Understanding why individuals adhere despite suboptimal CNB may provide novel insights into aspects influencing adherence.

HORMONAL CONTRACEPTION - USERS̕ KNOWLEDGE Student: Křiklánová, J. Tutor: Marešová, H. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic Introduction: Hormonal contraception is a broadly used and very reliable birth control method. Nonetheless, it is not entirely risk-free. This thesis deals with the awareness of those risks in women who are currently using hormonal contraception or have ever used it before. Aim of the thesis: The main aim was to determine the extent of the users' awareness of hormonal contraception and its risks, undesirable side effects and contraindications, as well as their source of information. Furthermore, the awareness of the environmental impact, the reasons for using hormonal contraception and user satisfaction were examined. Methodology: The research was carried out by means of online questionnaires, which were spread among current or former users of hormonal contraception regardless of age, educational background or place of residence. 148 completed questionnaires were gathered and the data which were obtained were statistically evaluated. Results: It was discovered that women feel informed (25 %) or rather informed (44,6 %) more often than uninformed; the most frequent source of information is patient...