Made available in DSpace on 2014-06-11T19:29:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T20:20:21Z : No. of bitstreams: 1 poiati_jr_me_botfm.pdf: 349678 bytes, checksum: 1fc38334d96bc4cfd845a4843dbc402b (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O novo conceito de pré-eclâmpsia precoce e tardia estabeleceu a hipótese de que essas duas entidades possam estar associadas a diferentes modelos de adaptação vascular. A tonometria de aplanação é capaz de avaliar, de forma não invasiva, diversas características vasculares e pode ser utilizada para estudar a fisiopatologia das diferentes formas de pré-eclâmpsia. Comparar as características vasculares de gestantes portadoras de pré-eclâmpsia precoce e tardia, determinadas por meio da tonometria de aplanação. Estudo transversal e analítico realizado em 85 gestantes portadoras de pré-eclâmpsia (PE) que, no momento do diagnóstico, foram estratificadas em PE precoce e tardia, de acordo com a idade gestacional da manifestação clínica da doença. O cálculo do tamanho amostral foi baseado no estudo de Khalil et al. (2009) e estimado em 33 pacientes por grupo. Considerou-se o nível de significância de 5% (α = 0,05) e o poder de 80% (β = 0,20). Foram avaliadas a pressão arterial periférica e central, a pressão de pulso periférica e central, o índice de amplificação, a pressão de aumento, o índice de viabilidade subendocárdica e a duração de ejeção. Todos os índices foram determinados por meio da tonometria de aplanação (SphygmoCor®). A análise estatística foi feita no programa SPSS 10.5. As variáveis foram representadas por média e desvio padrão, mediana e porcentagem. A média foi utilizada para variáveis com distribuição normal e a mediana para variáveis que não apresentaram distribuição normal. Para a comparação das médias dos grupos pré-eclâmpsia precoce e tardia foi utilizado o teste t de Student e, quando necessário, o teste de Mann-Whitney. Para comparação das proporções foi utilizado o teste de qui-quadrado. Foi considerado nível de significância de 5%. Considerando-se as características da população estudada verificou-se... / The new concept of early and late preeclampsia established the hypothesis that these two entities may be associated with different models of vascular adaptation. The applanation tonometry is able to evaluate, noninvasively, several vascular features and can be used to study the pathophyology of different forms of preeclampsia. To compare vascular characteristics of pregnant women with early and late preeclampsia, determined by applanation tonometry. Cross sectional and analytical study conducted in 85 pregnant women with preeclampsia (PE) that, at the time of diagnosis, were stratified into early and late PE, according to the gestational age of the clinical manifestation of the disease. The calculation of the sample size was based on the study of Khalil et al. (2009) and estimated at 33 patients per group. It was considered the significance level of 5% (α = 0.05) and 80% power (β = 0.20). It was also evaluated the peripheral and central blood pressure, peripheral and central pulse pressure, augmentation index, the augmentation pressure, subendocardial viability ratio and the ejection duration. All indexes were determined by applanation tonometry (SphygmoCor ®). Statistical analysis were done using SPSS 10.5. Variables were presented as mean and standard deviation, median and percentage. The mean was used for variables with normal distribution and median for variables that did not show normal distribution. For the comparison of the mean in the group with early and late preeclampsia it was used a student t test and, when necessary, the Mann-Whitney test. To compare proportions it was used the qui-quadrado test. It was considered a significance level of 5%. Considering the characteristics of the population studied it was verified that body mass index, proteinuria and gestational age were significantly different between the groups. As for the vascular features determined by applanation... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:30:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-03-02Bitstream added on 2014-06-13T20:21:28Z : No. of bitstreams: 1 lourenco_ncv_dr_botib.pdf: 289471 bytes, checksum: 1e3de2164fad680893ad0ff7aece51c7 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A pré-eclâmpsia é uma síndrome específica da gestação humana, caracterizada por hipertensão arterial e proteinúria após a 20ª. semana de gestação. É aceito que esta patologia tem origem na placenta. O fator de crescimento placentário (PlGF) tem importante papel no desenvolvimento vascular durante a invasão trofoblástica e, citocinas de perfil Th2 podem estar envolvidas na manutenção da gestação durante a interação materno-fetal.O presente trabalho avaliou a concentração de citocinas e de fatores pró e anti-angiogênicos em homogenato de placenta, obtido de gestantes normais e com pré-eclâmpsia, correlacionando esses parâmetros com a gravidade da doença e com a idade gestacional.Foram estudadas 70 gestantes, sendo 30 normotensas e 40 portadoras de pré-eclâmpsia. As gestantes com pré-eclâmpsia foram classificadas de acordo com o aparecimento das manifestações clínicas em pré-eclâmpsia precoce (< 34 semanas de gestação, n=13) e pré-eclâmpsia tardia (≥ 34 semanas de gestação, n=27). Um fragmento de placenta foi obtido imediatamente após o parto, homogeneizado em solução salina tamponada com fosfatos e submetido à centrifugação. O sobrenadante obtido foi empregado para determinação de fator de necrose tumoral-alfa (TNF-a), fator estimulador de colônias de granulócitos e macrófagos (GM-CSF), interleucina-10 (IL-10), fator de crescimento e transformação beta (TGF-b1), fator de crescimento placentário (PlGF) e Endostatina por ensaio imunoenzimático (ELISA). Outro fragmento placentário foi obtido para análise histopatológica. As diferenças entre os grupos de gestantes normais e com préeclâmpsia foram avaliadas por teste t de Student, com nível de significância de 5%.Os níveis de TNF-a, Endostatina e GM-CSF detectados na placenta de gestantes com pré-eclâmpsia foram significativamente maiores em relação às gestantes... / Preeclampsia is a human pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria after the 20th gestational week. It is widely accepted that this disorder is placental in origin. Placental growth factor (PlGF) plays an important role in the vascular development during trophoblast invasion and cytokines with Th2 profile may be involved in gestation maintenance and promoting a balance in maternal– fetal interaction. This study investigated the concentration of cytokines, angiogenic and anti-angiogenic factors in placental homogenate obtained from normotensive and preeclamptic pregnant women, and correlated these parameters with disease severity and gestational age.The subjects were 70 pregnant women of whom 30 were normotensive pregnant, and 40 were pregnant women with preeclampsia. The preeclamptic pregnant women were classified according to the onset of clinical manifestations in early-onset (< 34 weeks of gestation, n=13) and late-onset (≥ 34 weeks of gestation, n=27) preeclampsia. A tissue fragment of the placenta was obtained immediately after delivery, homogenized with phosphate-buffered saline solution and centrifuged. Separated supernatant was employed for determination of tumor necrosis factor alpha (TNF-a), granulocyte-macrophage colony-stimulating factor (GM-CSF) Interleukin-10 (IL-10), transforming growth factor beta (TGF-b1), placental growth factor (PlGF), and Endostatin, by enzyme-linked immunosorbent assay (ELISA). Another placental tissue segment was prepared for histopathological analysis. Differences between groups were evaluated by Student t unpaired test with significance set at p < 0.05.The levels of TNF-a, Endostatin and GM-CSF detected in placenta of preeclamptic women were significantly increased when compared with the normotensive pregnant women. On the other hand, the concentration of IL-10, TGF-b1 and PlGF have shown... (Complete abstract click electronic access below)

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 82-89).

Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T18:47:26Z : No. of bitstreams: 1 martins_rar_me_botfm.pdf: 360919 bytes, checksum: cbb7d98cabd32fdfd936feb6aba67c10 (MD5) / A pré-eclâmpsia é uma complicação grave da gestação, caracterizada por hipertensão e proteinúria. Os sintomas desta síndrome aparecem durante a segunda metade da gestação. A literatura sugere que a pré-eclâmpsia resulta de uma resposta inflamatória excessiva à gestação. O objetivo deste trabalho foi avaliar a atividade de monócitos de sangue periférico através da produção de citocinas, atividade fungicida e liberação de peróxido de hidrogênio por essas células em gestantes normais e com pré-eclâmpsia. Foram estudadas 25 mulheres não-grávidas e normotensas e 50 gestantes sendo 20 normotensas e 30 com pré-eclâmpsia. Monócitos foram cultivados com ou sem 10 ug/mL de lipopolissacáride (LPS) durante 24 h a 37oC e os níveis de fator de necrose tumoral alfa (TNF-a), de Interleucina-10 (IL -10) e de fator transformador do crescimento beta (TGF-b1) foram determinados no sobrenadante de cultura por ensaio imunoenzimático. A atividade fungicida foi avaliada pela recuperação de células viáveis de Candida albicans após plaqueamento e contagem de unidades formadoras de colônias em meio ágar Sabouraud. A liberação de peróxido de hidrogênio (H2O2) foi determinada antes e após estímulo dos monócitos com phorbol 12-myristate 13-acetate (PMA). Os resultados mostraram que os níveis endógenos de TNF-a, IL -10 e de TGF-b1 produzidos por monócitos, cultivados sem estímulo, foram significativamente mais elevados tanto em gestantes normais como nas com pré-eclâmpsia. Resultados semelhantes foram observados com relação à produção de IL-10 e TGF-b1 por monócitos após estímulo com LPS. A liberação de H2O2 após estímulo com PMA foi mais elevada em gestantes normais do que nas com pré-eclâmpsia. Além disso, monócitos de gestantes com... / Pre-eclampsia is a severe complication of pregnancy, characterized by hypertension and proteinuria. The symptoms of this syndrome appear during the second half of the pregnancy. The literature suggests that pre-eclampsia results from an excessive maternal inflammatory response to pregnancy. The objective of this study was to evaluate the activity of peripheral blood monocytes by cytokine production, fungicidal activity and hydrogen peroxide liberation in normotensive pregnant women and with pre-eclampsia. The study included 25 normotensive non-pregnant and 50 pregnant women being 20 normotensive and 30 with preeclampsia. Monocytes from these women were cultivated with or without 10 ug/mL lipopolysaccharide (LPS) during 24h at 37oC, and the levels of tumor necrosis factor-alpha (TNF-a), Interleukin-10 (IL -10) and transforming growth factor beta 1 (TGF-b1) were determined in culture supernatants by enzyme immunoassay. The fungicidal activity was determined by the recovery of viable Candida albicans after co-culture of yeasts with monocyte and plating in Sabouraud medium with enumeration of colony forming units. Hydrogen peroxide (H2O2) liberation was determined before and after monocyte stimulation with phorbol 12-myristate 13- acetate (PMA). The results showed that endogenous levels of TNF-a, IL-10 and TGF-b1 detected in supernatants of monocytes cultivated without stimulus were significantly higher in both normal and pre-eclampsia pregnant patients than in non-pregnant women. Similar results were observed in relation to IL -10 and TGF- b1 production after monocyte stimulation with LPS. Monocytes from normotensive pregnant women released higher levels of H2O2 after PMA stimulation than cells from patients with pre-eclampsia. Besides monocytes from women with preeclampsia produced lower levels of TNF-a suggesting an impairment in the... (Complete abstract click electronic address below)

Made available in DSpace on 2014-06-11T19:29:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-02Bitstream added on 2014-06-13T18:39:54Z : No. of bitstreams: 1 freitas_ma_me_botfm.pdf: 331447 bytes, checksum: 66d83c3fa149c9173a912ac0db893ee1 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Durante sua evolução a pré-eclâmpsia (PE) pode agravar-se pelo desenvolvimento dos sinais de eclâmpsia iminente (distúrbios do sistema nervoso central, visuais e gástricos). Os distúrbios visuais caracterizam-se por escotomas, fosfenas, embaçamento da visão e até amaurose. O exame de fundo de olho mostra alterações decorrentes do vasoespasmo, características da fisiopatologia da doença. As alterações no fluxo dos vasos orbitais caracterizam patologias e ampliam o entendimento dos diferentes comprometimentos vasculares. Em gestantes, portadoras de PE, estudos de dopplervelocimetria mostram que os vasos orbitais estão comprometidos, auxiliando no entendimento da fisiopatologia desta doença e na diferenciação entre as formas de hipertensão arterial. Considerando que os sinais e sintomas da PE desaparecem espontaneamente após a resolução da gestação, o presente estudo teve como objetivo identificar se, no puerpério imediato de mulheres que manifestaram PE grave, as alterações de parâmetros do Doppler da artéria oftálmica apresentam sinais de involução. Foi realizado exame dopplervelocimétrico da artéria oftálmica de 52 mulheres portadoras de PE grave em dois momentos: na gestação e no puerpério imediato (24 e 48 horas após a resolução da gestação). Com um equipamento Toshiba Nemio 17 e transdutor linear na freqüência de 10 MHz avaliaram-se os seguintes parâmetros: índice de resistência (IR), índice de pulsatilidade (IP), pico de velocidade sistólica (PVS), pico de velocidade diastólica (PVD), pico de velocidade diastólica final (PVDF) e razão entre picos de velocidade (RPV). A análise estatística foi realizada aplicando-se os testes de Wilcoxon e Mann-Witney. Os resultados obtidos foram considerados significativos quando apresentaram valores de p <0,05. Os índices de resistência e de pulsatilidade foram significativamente maiores após... / Considering that the signs and symptoms of PE disappear spontaneously after the resolution of pregnancy, the present study is to identify if within the puerperium immediate women with severe PE, the changes parameters of ophthalmic Doppler artery show involution signals. 52 women with severe PE underwent the Dopller examination of ophthalmic artery at two different times: right before the interruption of pregnancy and within puerperium immediate (24 and 48 hours after the resolution of pregnancy). A Toshiba equipment and transductor Nemio 17 linear with a 10 MHz frequency evaluated the following parameters: resistance index (RI), pulsatility index (PI), systolic velocity peak (SVP), diastolic velocity peak (DVP), final diastolic velocity peak (FDVP) and ratio peak (RP). The results were subjected to statistical analysis using Wilcoxon and Mann-Witney tests, and they were considered significant when presented values of p < 0.05. RI and PI were significantly greater after resolution of pregnancy, while SVP, DVP and FDVP were significantly smaller after the resolution of pregnancy. There was no significant difference between the RP measured before and after the resolution pregnancy. The comparison of the parameters of the ophthalmic artery Doppler velocimetry before the resolution of pregnancy in women with PE, according to the absence and presence of uterine artery’s protodiastolic notch, showed a significant statistical difference only in relation to the RI, which showed an increase in the presence of protodiastolic notch. There was a tendency of PI value to be bigger in the presence of protodiastolic notch in uterine artery. The changes on the ophthalmic artery Doppler velocimetry indexes in women with severe PE, showed significant different values within the puerperium immediate, indicating early vascular changes involution produced by this disease during pregnancy. Pregnant women with... (Complete abstract click electronic access below)

Monoamine oxidase (MAO) is an outer mitochondrial membrane bound enzyme responsible for the oxidative deamination of a wide variety of biogenic and xenobiotic amines. Altered MAO activity has been reported in a number of medical and psychiatric disorders. Although the tissue distribution of these enzymes has been extensively studied, the localization of MAO proteins and mRNAs at the cellular level in peripheral tissues, including placenta, has not been fully established. In addition the status of placental MAO in pre-eclampsia - a severe disorder of pregnancy has not been fully studied, despite evidence of increased levels of circulating serotonin. This study investigated (a) the distribution of monoamine oxidase (MAO)-A and -B mRNAs and proteins in human peripheral tissues, by in situ hybridisation and immunohistochemistry, respectively, and (b) compared MAO activity, MAO protein and MAO specific mRNA in normotensive and preeclamptic individuals. For the latter, quantitative analyses involving ELISAs and RT-PCR were also conducted. MAO-A and -B mRNAs and proteins were detected in all peripheral tissues, but to differing extents, with similar, strong labelling in kidney glomeruli, duodenal crypts and muscularis mucosae and hepatocytes. However the expression of MAO mRNA does not always reflect protein expression. For example moderate labelling of MAO-A and B specific mRNAs was detected in blood vessels whereas the expression of respective MAO proteins was very low. In contrast, cardiomyocytes showed a moderate labelling for both MAO proteins, but a very weak staining for respective mRNAs. In normotensive placenta both MAO-A and -B specific mRNAs were detected, mainly in the syncytiotrophoblastic layers. The immunohistochemical analysis located only MAO-A protein in these layers. No MAO-B protein was detected in this placental layer, despite the presence ofMAO-8 mRNA. Likewise MAO-A protein was located in the cytoplasm ofthe pre-eclamptic placentae, consistent with a mitochondrial location; no MAO-A protein was found in the nucleus. The results indicate that there was no statistical difference in the expression of MAO-A mRNA in relation to GAPDH or B-actin mRNA or in MAO-A protein/mg total protein. However, MAO-A activity/g fresh weight and the catalytic turnover (activity/molecule) were significantly reduced [77% and 59% reductions, respectively (P< 0.05)], in pre-eclamptic placentae. This study has therefore clearly shown that the expression of placental MAO-A specific mRNA and MAO-A protein are not specifically affected in pre-eclampsia, but that the catalytic efficiency of the expressed MAO-A enzyme in pre-eclamptic placentae is greatly reduced.

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