Introdução: A principal causa de mortes maternas no Brasil são as Síndromes Hipertensivas na Gravidez (SHG). Estudos têm focado nos fatores de risco para essas síndromes, entretanto são pequenos e localizados. Um estudo de maior abrangência poderia encontrar valores mais precisos e diferenças entre seus estratos. Objetivo: Estimar a frequência das SHG na região sudeste do Brasil. Descrever e analisar os fatores associados às síndromes hipertensivas na gravidez. Método: Este é um estudo transversal, parte integrante do Nascer no Brasil: Inquérito Nacional sobre Parto e Nascimento, cuja coleta de dados ocorreu entre Fevereiro de 2011 e Julho de 2012. A amostra do estudo foi composta por todas as mulheres entrevistadas pelo inquérito em toda a região Sudeste do Brasil, totalizando 10154 pares de mulheres e conceptos. Resultados: As mulheres tinham entre 10 e 54 anos, predominantemente pardas/mulatas/morenas, não possuíam ensino superior, pertenciam à classe econômica C, tiveram seus bebê em hospitais das capitais e possuíam companheiro(a). De todos os nascimentos, 52,1 por cento ocorreram por cesariana, e destas 69,2 por cento sem que a mulher entrasse em trabalho de parto. Quase metade (43,9 por cento) dos nascimentos aconteceram antes que a gestação completasse 39 semanas. 77,7 por cento das mulheres relatam ter um acompanhante ao seu lado em algum momento durante o trabalho de parto/parto. As SHG acometeram 17,6 por cento de todas as mulheres. Destas, 3,4 por cento possuíam hipertensão crônica e a incidência de eclâmpsia foi de 1,6 por cento. Após análise multivariada, permaneceram independentemente associadas às SHG as variáveis cor preta (OR 1,4), histórico pessoal de eclâmpsia (OR 2,8), primiparidade (OR 1,6), diabetes (OR 2,3), mulheres com sobrepeso (OR 1,8), obesidade (OR 4,4) e gestação múltipla (OR 2,9). As mulheres com baixo peso apresentaram associação protetora (OR 0,6) Conclusões: Pode-se concluir que o histórico pessoal de eclâmpsia, diabetes, obesidade e gestação múltipla foram as variáveis que apresentaram maior associação com as SHG / Introduction: The main cause of maternal deaths in Brazil is hypertensive syndromes in pregnancy (HSP). Studies have focused on risk factors for these syndromes, however most are small-scaled and localized. A population-based study on the other hand, could potentially find more accurate results and differences between strata. Objective: To describe and analyze the incidence of HSP and the occurrence of associated factors in the Southeast of Brazil. Method: This is a cross-sectional study, part of \"Birth in Brazil: National Survey into Labor and Birth\" a national epidemiological survey on birthing in Brazil. Data collection took place between February 2011 and July 2012. The study sample consisted of all women interviewed for the survey across the southeastern region of Brazil, totaling 10,154 pairs of women and fetuses. Results: The women were between 10 and 54 years of age, predominantly brown skinned, with no graduation, in economic class C, had their babies in the hospitals placed on the capital cities and had a partner. 52.1 per cent of births occurred by cesarean section, 36 per cent without the woman going into labor. Almost half (43.9 per cent) of births occurred before 39 weeks of completed gestation. 77.7 per cent of women reported having a companion only sometimes during labor/delivery. HSP occurred in 17.6 per cent of all women, 3.4 per cent had chronic hypertension and the incidence of eclampsia was 1.6 per cent. After multivariate analysis, the independent variables associated with HSP is black skin (OR 1.4), personal history of preeclampsia (OR 2.8), primiparity (OR 1.6), diabetes (OR 2.3), underweight (OR 0.6), overweight (OR 1.8), obesity (OR) and multiple gestations (OR 2.9). Conclusion: The population-based data shows that a personal history of eclampsia, diabetes, obesity and multiple pregnancies were the variables with greater association with HSP

Introdução: A principal causa de mortes maternas no Brasil são as Síndromes Hipertensivas na Gravidez (SHG). Estudos têm focado nos fatores de risco para essas síndromes, entretanto são pequenos e localizados. Um estudo de maior abrangência poderia encontrar valores mais precisos e diferenças entre seus estratos. Objetivo: Estimar a frequência das SHG na região sudeste do Brasil. Descrever e analisar os fatores associados às síndromes hipertensivas na gravidez. Método: Este é um estudo transversal, parte integrante do Nascer no Brasil: Inquérito Nacional sobre Parto e Nascimento, cuja coleta de dados ocorreu entre Fevereiro de 2011 e Julho de 2012. A amostra do estudo foi composta por todas as mulheres entrevistadas pelo inquérito em toda a região Sudeste do Brasil, totalizando 10154 pares de mulheres e conceptos. Resultados: As mulheres tinham entre 10 e 54 anos, predominantemente pardas/mulatas/morenas, não possuíam ensino superior, pertenciam à classe econômica C, tiveram seus bebê em hospitais das capitais e possuíam companheiro(a). De todos os nascimentos, 52,1 por cento ocorreram por cesariana, e destas 69,2 por cento sem que a mulher entrasse em trabalho de parto. Quase metade (43,9 por cento) dos nascimentos aconteceram antes que a gestação completasse 39 semanas. 77,7 por cento das mulheres relatam ter um acompanhante ao seu lado em algum momento durante o trabalho de parto/parto. As SHG acometeram 17,6 por cento de todas as mulheres. Destas, 3,4 por cento possuíam hipertensão crônica e a incidência de eclâmpsia foi de 1,6 por cento. Após análise multivariada, permaneceram independentemente associadas às SHG as variáveis cor preta (OR 1,4), histórico pessoal de eclâmpsia (OR 2,8), primiparidade (OR 1,6), diabetes (OR 2,3), mulheres com sobrepeso (OR 1,8), obesidade (OR 4,4) e gestação múltipla (OR 2,9). As mulheres com baixo peso apresentaram associação protetora (OR 0,6) Conclusões: Pode-se concluir que o histórico pessoal de eclâmpsia, diabetes, obesidade e gestação múltipla foram as variáveis que apresentaram maior associação com as SHG / Introduction: The main cause of maternal deaths in Brazil is hypertensive syndromes in pregnancy (HSP). Studies have focused on risk factors for these syndromes, however most are small-scaled and localized. A population-based study on the other hand, could potentially find more accurate results and differences between strata. Objective: To describe and analyze the incidence of HSP and the occurrence of associated factors in the Southeast of Brazil. Method: This is a cross-sectional study, part of \"Birth in Brazil: National Survey into Labor and Birth\" a national epidemiological survey on birthing in Brazil. Data collection took place between February 2011 and July 2012. The study sample consisted of all women interviewed for the survey across the southeastern region of Brazil, totaling 10,154 pairs of women and fetuses. Results: The women were between 10 and 54 years of age, predominantly brown skinned, with no graduation, in economic class C, had their babies in the hospitals placed on the capital cities and had a partner. 52.1 per cent of births occurred by cesarean section, 36 per cent without the woman going into labor. Almost half (43.9 per cent) of births occurred before 39 weeks of completed gestation. 77.7 per cent of women reported having a companion only sometimes during labor/delivery. HSP occurred in 17.6 per cent of all women, 3.4 per cent had chronic hypertension and the incidence of eclampsia was 1.6 per cent. After multivariate analysis, the independent variables associated with HSP is black skin (OR 1.4), personal history of preeclampsia (OR 2.8), primiparity (OR 1.6), diabetes (OR 2.3), underweight (OR 0.6), overweight (OR 1.8), obesity (OR) and multiple gestations (OR 2.9). Conclusion: The population-based data shows that a personal history of eclampsia, diabetes, obesity and multiple pregnancies were the variables with greater association with HSP

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2015-10-22T13:41:11Z No. of bitstreams: 2 Tese - Glaucimeire Marquez Franco - 2015.pdf: 1831506 bytes, checksum: fc557ab2fef5a0036ed0efa86a2a0880 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-10-22T14:44:44Z (GMT) No. of bitstreams: 2 Tese - Glaucimeire Marquez Franco - 2015.pdf: 1831506 bytes, checksum: fc557ab2fef5a0036ed0efa86a2a0880 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-10-22T14:44:44Z (GMT). No. of bitstreams: 2 Tese - Glaucimeire Marquez Franco - 2015.pdf: 1831506 bytes, checksum: fc557ab2fef5a0036ed0efa86a2a0880 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-03-07 / Introduction: Preeclampsia and eclampsia are important causes of maternal and perinatal morbidity and mortality worldwide Objectives: To evaluate the maternal brain centralization in pregnant women with specific gestational hypertension. Produce a systematic review article on the ophthalmic artery Doppler and uterine artery and the flow-mediated dilation. Develop an original article in order to assess the possible occurrence of maternal brain centralization in pregnant women with specific gestational hypertension. Establish normal values of the ratio of uterine artery to the ophthalmic artery (mean and standard deviation). Compare the ratio of uterine with the ophthalmic artery in normal and pathological group. Set the cut-off point, using the ROC curve for specific diagnosis of patients with hypertensive disease of pregnancy. Methods: A systematic literature review involved 260 indexed articles from Medline via PubMed and Virtual Health Library (VHL), published between 1989 and 2014. For the original article, we performed a case-control study of 178 pregnant women divided into two groups: a control group of normal patients (PN), a total of 83 normotensive pregnant women; and one case group of 95 patients with specific gestational hypertension. The analyzed parameters which formed part of the variables studied were: systolic velocity (VS), diastolic velocity (RV), the resistance index, systole-diastole relationship. In addition to these variables were also studied epidemiological variables of pregnancy, parity, abortion, weight, height, BMI, maternal age, gestational age. Results: Through the search strategy, were located 260 articles, of which 33 articles were eligible, with fifteen articles on the ophthalmic artery, eight articles on the brachial artery and eight articles on uterine artery. A total of 178 patients took part in study. The average age of normal pregnant women group of patients was 29.8 ± 4.7 and patients with specific gestational hypertension, of 26.14 ± 6.17. The mean gestational age of normal pregnant patients was 34.3 ± 3.5 weeks and the patients with specific gestational hypertension, of 32.40 ± 3.37. The mean body mass index (BMI) of healthy patients was 26.8 ± 5.6 and patients with specific gestational hypertension, of 30.55 ± 5.12. A normality curve systole-diastole compared with the respective cutoff was performed. A ROC curve was developed, with the cutoff point, considering the systolic velocity, diastolic velocity, systolic-diastolic ratio and the resistance index of the ophthalmic artery, respectively. Conclusion: The Doppler uterine artery and ophthalmic artery flow-mediated dilatation can be useful to identify patients at risk for allowing the monitoring of disease progression and perform effective interventions. It is observed that the possibility of maternal centralization in high-risk pregnancy as the PE is real, whereas in the average normal values and the standard deviation of the Doppler AU / AO-systole-diastole ratio were 0.43 ± 0 16. The cutoff point more sensitive, verified by the ROC curve, which defines maternal brain centralization in patients with hypertensive disorders of pregnancy, is 0.57 for the S / D for UD / AO, with 78% sensitivity and 13 % false positive and 77% specificity. / Introdução: A pré-eclâmpsia é um importante problema em obstetrícia, com altos índices de morbidade perinatal e mortalidade em todo o mundo, principalmente nos países em desenvolvimento. Objetivos: Avaliar a ocorrência de centralização cerebral materna em gestantes portadoras de doença hipertensiva específica da gestação. Produzir um artigo de revisão sistemática sobre Doppler da artéria oftálmica e da artéria uterina e sobre a dilatação fluxo-mediada da artéria braquial. Elaborar um artigo original para avaliar a ocorrência da centralização cerebral materna em gestantes portadoras de doença hipertensiva específica da gestação. Estabelecer a curva de normalidade da relação do Doppler da artéria uterina com o Doppler da artéria oftálmica. Comparar a relação do Doppler da uterina com o Doppler da artéria oftálmica no grupo normal e patológico. Definir o ponto de corte, através da curva ROC, para diagnóstico de pacientes com doença hipertensiva específica da gestação. Métodos: A revisão sistemática da literatura envolveu 260 artigos indexados das bases de dados Medline via PubMed e Biblioteca Virtual em Saúde (BVS), publicados entre 1989 e 2014. Para o artigo original, foi realizado um estudo caso controle com 178 gestantes distribuídas em dois grupos: um grupo-controle de pacientes normais (PN), num total de 83 gestantes normotensas; e um grupo casos de 95 pacientes com doença hipertensiva específica da gestação. As variáveis estudadas foram: a velocidade sistólica (VS), a velocidade diastólica (VD), o índice de resistência, a relação sístole-diástole. Além dessas variáveis foram estudadas paridade, aborto, peso, altura, IMC, idade materna, idade gestacional. Resultados: Por meio da estratégia de busca, localizaram-se 260 artigos, dos quais foram elegíveis 32 artigos, sendo dezesseis artigos sobre a artéria oftálmica, oito artigos sobre a artéria braquial e oito artigos sobre a artéria uterina. Um total de 178 pacientes fez parte do estudo. A média de idade das pacientes do grupo de gestantes normais foi de 29,8±4,7 e das pacientes com doença hipertensiva específica da gestação, de 26,14±6,17. A média da idade gestacional das pacientes gestantes normais foi de 34,3±3,5 semanas e das pacientes com doença hipertensiva específica da gestação, de 32,40±3,37. A média do índice de massa corporal (IMC) das gestantes normais foi de 26,8±5,6 e das pacientes com doença hipertensiva específica da gestação, de 30,55±5,12. Foi realizada uma curva de normalidade da relação sístole-diástole com o respectivo ponto de corte. Desenvolveu-se uma curva ROC com o ponto de corte, considerando a velocidade sistólica, a velocidade diastólica, a relação sístole-diástole e o índice de resistência da artéria oftálmica, respectivamente. Conclusão: O Doppler da artéria oftálmica e da artéria uterina e a dilatação fluxo mediada podem ser úteis para identificar pacientes em risco. Observou-se que a ocorrência de centralização materna em gravidez de alto risco como a pré-eclâmpsia (PE) é real, visto que na curva de normalidade a média e o desvio padrão do Doppler da AU/AO da relação sístole-diástole foram de 0,43 ± 0,16. O ponto de corte mais sensível, verificado por meio da curva ROC, que define centralização cerebral materna nas pacientes com doença hipertensiva específica da gestação, é de 0,57 para a S/D da UD/AO, com 78% de sensibilidade e 13% de falso positivo e 77% de especificidade.

Excessive release of syncytiotrophoblast vesicles (STBM) from the placenta into the maternal circulation may cause the inflammatory response, endothelial dysfunction and activation of the coagulation system characteristic of pre-eclampsia (PE). Consequently, other cell types including platelets, leukocytes, red blood cells (RBC) and endothelium may be activated to release cellular vesicles which exacerbate the disease. This thesis aimed to develop methodology for enumerating and phenotyping STBM and the other vesicle types to determine whether they could be used as biomarkers for PE. In vitro derived STBM and vesicles from the other cells of the vascular compartment were examined to select a suitable panel of antibodies to analyse these same vesicle types in plasma samples from non-pregnant (NonP), normal pregnant (NormP) and PE women. Our flow cytometer was shown to detect microvesicles ≥290nm, hence smaller nanovesicles and exosomes could not be detected by this method. Therefore, a novel technique for analysing both microvesicles and nanovesicles, Nanoparticle Tracking Analysis (NTA), was explored and was found to be able to detect vesicles as small as 70nm. The origins of the vesicles that change in pregnancy are not yet known. Flow cytometry and NTA were used in parallel to determine the size, number and phenotype of STBM and other cellular vesicles in NonP, NormP and PE women. Flow cytometry showed that majority of vesicles were derived from platelets, followed by RBC vesicles, leukocyte vesicles and STBM. NTA showed that the total number of vesicles in plasma was significantly elevated in NormP and late-onset PE women compared to NonP controls, and the vesicles were smaller in size. Similarly, flow cytometry showed differences in the composition of vesicles between pregnant and non-pregnant women, demonstrating that pregnancy affects vesicle release. However, no differences were found between NormP and PE women. This was probably due to the majority of samples studied being from late rather than early-onset PE. Thus, although this is the most comprehensive analysis of circulating vesicles in pregnancy to date, their use as biomarkers for PE remains an open question.

Eclampsia is a hypertensive disorder of pregnancy and a leading cause of maternal death. The primary explanation for eclampsia is that it represents a form of hypertensive encephalopathy (HTE) with neurological symptoms including headaches, nausea, vomiting, visual disturbances, and seizures. The etiology of HTE involves an acute increase in arterial blood pressure that exceeds the autoregulatory capacity of the brain leading to forced dilatation of cerebral vessels, decreased cerebrovascular resistance, hyperperfusion, blood-brain barrier (BBB) disruption, and vasogenic cerebral edema formation. Due to the central role of the cerebral circulation in mediating these symptoms, a better understanding of how pregnancy affects the cerebral circulation is important to the treatment and prevention of eclampsia. A central goal of this dissertation was to determine pregnancy’s effect on cerebral blood flow (CBF) autoregulation, edema formation, and BBB permeability during acute hypertension. Women with eclampsia often seize at lower blood pressures than HTE patients. We hypothesized that pregnancy may predispose the brain to eclampsia by lowering the pressure of autoregulatory breakthrough and enhancing cerebral edema formation. Using an in vivo model of HTE, we found that the pressure of autoregulatory breakthrough was not different between nonpregnant (NP) and late-pregnant (LP) rats; however, cerebral edema formation was significantly increased only in LP animals. Nitric oxide synthase inhibition significantly increased the upper limit of autoregulation in both NP and LP animals and attenuated cerebral edema formation in LP animals. BBB permeability during acute hypertension was not different between these groups. Magnesium sulfate (MgSO4) is widely used to treat eclampsia despite an unclear mechanism of action. A second goal of this dissertation was to determine the cerebrovascular effects of MgSO4 during pregnancy. Specifically, we investigated the effect of MgSO4 on in vitro resistance artery vasodilation and in vivo BBB permeability during acute hypertension. We hypothesized that dilation to MgSO4 would be greater in mesenteric than cerebral vessels. MgSO4 elicited concentration-dependent vasodilation in all arteries, as determined by measuring lumen diameter of isolated and pressurized arteries, however, mesenteric arteries were considerably more sensitive than cerebral arteries. In addition, there was no effect of pregnancy on MgSO4 sensitivity in mesenteric arteries, whereas pregnancy decreased sensitivity to MgSO4 in cerebral arteries. We further hypothesized that MgSO4 would decrease BBB disruption during acute hypertension, thereby protecting the brain in eclampsia. Using an in vivo model of HTE, we showed that MgSO4 treatment decreased BBB permeability during acute hypertension in LP rats, with the greatest effect observed in the posterior cerebrum. In conclusion, this dissertation determined CBF autoregulation and cerebral edema formation during pregnancy, and also the effect of MgSO4 on cerebral resistance artery vasodilation and BBB permeability during acute hypertension in LP rats. Although pregnancy did not influence autoregulatory breakthrough, cerebral edema formation was enhanced in LP animals and this may potentiate neurological symptoms in eclampsia. In addition, MgSO4-induced cerebral vasodilation is likely not a primary mechanism of eclampsia treatment, rather MgSO4 may limit edema formation by attenuating BBB permeability during hypertension.

Dissertation for MMed (Obstetrics and Gynaecology) and FCOG Part II / Hypertensive disorders in pregnancy are common and their incidence appears to be on the increase. Preeclampsia is a multi-organ, heterogeneous disorder of pregnancy associated with significant maternal, fetal and neonatal morbidity and mortality. Because preeclampsia is a progressive disorder, invariably delivery remote from term is often necessary to halt disease progression to benefit the mother and fetus. Objectives:  To determine the maternal outcomes in women with severe preeclampsia  To determine fetal and neonatal outcomes of infants born preterm Methods This was a prospective, descriptive study performed in three academic hospitals affiliated to the University of the Witwatersrand in Johannesburg. Data was collected from women with severe preeclampsia, who delivered between gestational ages of 26 weeks and 33 weeks, with a minimum neonatal weight of 500g as determined by sonography. Results: In the sample of 92 patients enrolled, there were two maternal deaths as a result of severe preeclampsia. Eclampsia and HELLP syndrome were the most frequently observed maternal complications at 34% and 49% respectively. Caesarean section was the most frequent method used to expedite delivery in 84% of women. Of the 97 babies delivered, 20% were confirmed intra-uterine fetal deaths, 7% demised during the early neonatal period and a there was a 40% very low birth weight rate. Conclusion: Despite interventions to reduce maternal and neonatal morbidity and mortality in our setting, our outcomes are similar to those observed in other parts of the world.

by Wong Wah-Kwan, Herman. / Thesis (M.Phil.)--Chinese University of Hong Kong. / Includes bibliographical references (leaves 69-79). / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Pregnancy-induced hypertension --- p.2 / Chapter 1.1a --- Definition of pregnancy-induced hypertension --- p.2 / Chapter 1.2 --- A brief history of pregnancy-induced hypertension --- p.5 / Chapter 1.3 --- The epidemiology of pregnancy-induced hypertension --- p.6 / Chapter 1.4 --- Prediction of pregnancy-induced hypertension --- p.8 / Chapter 1.5 --- Erythrocyte sodium-lithium countertransport --- p.14 / Chapter 1.5.1 --- The history and characteristics of SLC --- p.14 / Chapter 1.5.2 --- SLC in essential hypertension --- p.19 / Chapter 1.5.3 --- SLC in pregnancy --- p.26 / Chapter 1.5.4 --- SLC in other diseases --- p.27 / Chapter 1.6 --- Methods used in the study of erythrocyte SLC --- p.32 / Chapter 1.7 --- Aims of the projects --- p.34 / Chapter CHAPTER 2 --- MATERIALS & METHODS --- p.35 / Chapter 2.1 --- Anthropometric measurements --- p.36 / Chapter 2.1.1 --- Blood pressure measurements --- p.36 / Chapter 2.1.2 --- Physical measurements --- p.36 / Chapter 2.1.3 --- Gestational age --- p.36 / Chapter 2.2 --- Materials --- p.37 / Chapter 2.3 --- Method for the measurement of erythrocyte SLC --- p.37 / Chapter CHAPTER 3 --- PRECISION & INTRA-INDIVIDUAL VARIATION OF ERYTHROCYTE SLC IN MALES & FEMALES --- p.42 / Chapter 3.1 --- Assessment of the precision of the methods --- p.43 / Chapter 3.2 --- Method of study --- p.45 / Chapter 3.3 --- Statistics --- p.46 / Results --- p.47 / Chapter CHAPTER 4 --- PREDICTION OF PREGNANCY-INDUCED HYPERTENSION: SLC ACTIVITIES IN SECOND & THIRD TRIMESTERS --- p.54 / Chapter 4.1 --- Method of Study --- p.55 / Chapter 4.2 --- Results --- p.55 / Chapter CHAPTER 5 --- DISCUSSION --- p.63 / REFERENCES --- p.69

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Yim Ka Wing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 93-102). / Abstracts in English and Chinese. / Statement --- p.I / Abstract --- p.Ii / Acknowledgements --- p.Iv / Publications and awards --- p.Vii / General abbreviations --- p.Viii / Technical abbreviations --- p.Ix / Abbreviations of chemicals --- p.X / List of figures --- p.Xi / List of tables --- p.Xiii / Table of contents --- p.Xiv / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Pre-eclampsia --- p.3 / Chapter 2.1 --- Inadequate Uteroplacental Circulation --- p.5 / Chapter 2.2 --- Placenta Ischaemia --- p.7 / Chapter 2.3 --- Oxidative Stress --- p.7 / Chapter 2.4 --- Systemic Inflammatory Response --- p.9 / Chapter 2.5 --- The Continuum Theory of Clinical Syndromes --- p.12 / Chapter 2.6 --- Origin of Stimuli to Inflammatory Response --- p.13 / Chapter Chapter 3 --- Proteomic Analysis --- p.16 / Chapter 3.1 --- Methodology in Proteomic Research --- p.17 / Chapter 3.1.1 --- 2D-PAGE --- p.17 / Chapter 3.1.2 --- Mass Spectrometry --- p.18 / Chapter 3.1.2.1 --- Peptide Mass Fingerprinting --- p.18 / Chapter 3.1.2.2 --- Product-ion Data --- p.19 / Chapter 3.1.2.3 --- Matrix-assisted Laser Desorption/Ionization Tandem Time-of-Flight Mass Spectrometry (MALDI-TOF/TOF MS) --- p.19 / Chapter 3.1.3 --- Bioinformatics Tools --- p.20 / Chapter 3.2 --- Applications of Proteomic Analysis --- p.20 / Chapter Chapter 4 --- Materials and Methods --- p.21 / Chapter 4.1 --- Overview --- p.21 / Chapter 4.2 --- Patients --- p.23 / Chapter 4.2.1 --- Pre-eclampsia --- p.23 / Chapter 4.2.2 --- Recruitment --- p.23 / Chapter 4.3 --- Stage I: Comparative Proteomic Analysis --- p.24 / Chapter 4.3.1 --- Sample Processing --- p.24 / Chapter 4.3.2 --- Modified Bradford's Method --- p.24 / Chapter 4.3.3 --- Albumin Depletion --- p.25 / Chapter 4.3.4. --- Comparative Proteomic Analysis --- p.26 / Chapter 4.3.4.1 --- First Dimension: Isoelectric Focusing (IEF) --- p.28 / Chapter 4.3.4.2 --- Reduction and Alkylation --- p.29 / Chapter 4.3.4.3 --- Second Dimension: SDS-PAGE --- p.30 / Chapter 4.3.4.4 --- Gel Imaging --- p.31 / Chapter 4.3.5 --- 2D-PAGE Data Analysis --- p.32 / Chapter 4.3.5.1 --- Gaussian Spot --- p.32 / Chapter 4.3.5.2 --- Matchset --- p.33 / Chapter 4.3.5.3 --- Normalization --- p.33 / Chapter 4.3.5.4 --- Significance Analysis of Microarrays --- p.34 / Chapter 4.4 --- Stage II: Protein Identification --- p.35 / Chapter 4.4.1 --- Tryptic Peptide Fingerprinting --- p.37 / Chapter 4.4.1.1 --- Removal of Silver Ions --- p.37 / Chapter 4.4.1.2 --- Reduction and Alkylation --- p.38 / Chapter 4.4.1.3 --- In-gel Digestion --- p.38 / Chapter 4.4.1.4 --- Clean up of Peptides --- p.39 / Chapter 4.4.1.5 --- Mass Spectrometric Analysis --- p.39 / Chapter 4.4.2 --- Database search: Profound-Peptide Mapping --- p.40 / Chapter 4.4.3 --- Database search: Mascot-MS/MS Ion Search --- p.40 / Chapter 4.5 --- Stage III: Immunoassays --- p.41 / Chapter 4.6 --- Sample Size and Power Calculations --- p.42 / Chapter 4.7 --- Statistical Analysis --- p.42 / Chapter Chapter 5 --- Results --- p.43 / Chapter 5.1 --- Patients' Demographic Characteristics and Obstetric Outcomes for 2D-PAGE Analysis --- p.43 / Chapter 5.2 --- Plasma Protein Quantity --- p.45 / Chapter 5.3 --- 2D-PAGE --- p.47 / Chapter 5.4 --- SAM Analysis --- p.47 / Chapter 5.5 --- Spot # 5204 and Spot # 6210 --- p.50 / Chapter 5.6 --- Protein Identification --- p.54 / Chapter 5.6.1 --- Identification of Protein Spot # 5204 --- p.54 / Chapter 5.6.2 --- Identification of Protein Spot # 6210 --- p.61 / Chapter 5.7 --- Patients' Demographic Characteristics and Obstetric Outcomes for Immunoassays --- p.68 / Chapter 5.8 --- Immunoassays --- p.70 / Chapter Chapter 6 --- Discussion --- p.81 / Chapter 6.1 --- Role of ficolins and MBL in complement activation pathway --- p.82 / Chapter 6.2 --- Structure of ficolins and MBL --- p.83 / Chapter 6.2.1 --- H-ficolin --- p.85 / Chapter 6.2.2 --- L-ficolin --- p.86 / Chapter 6.3 --- Immune Response and Pre-eclampsia --- p.86 / Chapter 7 --- Conclusion --- p.89 / Appendix --- p.90 / References --- p.93

Introducción: La enfermedad Hipertensiva del Embarazo (EHE) -pre-eclampsia y eclampsia- provoca cambios en muchos órganos y sistemas del organismo, incluido los órganos de la visión, que son susceptibles de ser evaluados por examen de fondo de ojo. Algunos estudios reportan que el síntoma visual más común en la EHE es la visión borrosa, fotopsias, escotomas y diplopía, y los signos más frecuentemente hallados son anormalidades arteriolares, desprendimientos serosos de la retina, y neuropatía óptica isquémica. Materiales y Métodos: Se realizó un estudio observacional, analítico y retrospectivo, donde se evaluaron el fondo de ojo de 363 pacientes con diagnóstico de EHE del servicio de Gineco-Obstetricia del Hospital Nacional María Auxiliadora durante el periodo comprendido de junio del 2007 hasta mayo del 2010. El objetivo principal del estudio fue determinar la prevalencia de alteraciones en el fondo de ojo asociadas a hipertensión arterial inducida por el embarazo, así como determinar la asociación entre el grado de severidad de la Retinopatía y el Grado de Severidad de la Hipertensión Arterial. Resultados: Se evaluaron 363 pacientes con diagnóstico de EHE, con una edad media de 27.54 (Desviación típica =7.01 y Rango, 14 - 46) años. Ellas fueron tratadas en el departamento de Gíneco - Obstetricia del Hospital María Auxiliadora, a partir de junio de 2007 a mayo del 2010. La edad media de gestación fue de 37,0 ± 2,8 semanas (rango, 28-39). Basado en el examen oftalmoscópico del fondo de ojo, las pacientes fueron divididas en cuatro grupos, según el sistema de Keith-Wegener-Baker para retinopatía hipertensiva. De las 363 mujeres analizadas, 238 (65.56%) no presentaron alteración en el fondo de ojo, en 125 (34.44%) pacientes se encontró algún grado de Retinopatía Hipertensiva. 67 de ellas fueron clasificados como grado I, 33 de grado II, 16 de grado III y 9 de grado IV. 263 pacientes presentaron pre-eclampsia leve, 89 pacientes tuvieron pre-eclampsia severa y 11 tuvieron eclampsia. Discusión: Se observó una correlación estadísticamente significativa (Correlación de Spearman) entre el grado de retinopatía hipertensiva y la severidad de la hipertensión arterial. Así también se halló asociación estadísticamente significativa entre la presencia de sintomatología y la presencia de alteración en el fondo de ojo (Chi2, p <0,001). Conclusiones: Existe una correlación estadísticamente significativa entre el grado de severidad de la retinopatía hipertensiva y el grado de severidad del estado hipertensivo del embarazo. El examen de fondo de ojo en pacientes pre-eclámpticas y eclámpticas, provee datos clínicos importantes que permiten un seguimiento y tratamiento apropiado de las pacientes. Palabras Clave: Retinopatía Hipertensiva, Pre-eclampsia, Eclampsia / Tesis de segunda especialidad