Orientador: Maria Terezinha Serrão Peraçoli / Banca: José Carlos Peraçoli / Banca: Joélcio Francisco Abbade / Banca: Nilton Hideto Takiuti / Resumo: Silibinina é um flavonóide quimicamente definido e o principal componente ativo da silimarina, um complexo polifenólico obtido de frutos e sementes de Silybum marianum, que possui propriedades anti-inflamatória, hepatoprotetora e anti-carcinogênica. Objetivo: O objetivo deste trabalho foi avaliar os efeitos da silibinina sobre a performance reprodutiva de ratas prenhes Wistar e as anomalias e/ou malformações de seus fetos. Métodos: Foram utilizadas ratas Wistar prenhes estratificadas em quatro grupos experimentais: controle (n = 6), ratas tratadas com 50mg/kg/dia de silibinina (Grupo I, n = 6), ratas tratadas com 100mg/kg/dia de silibinina (Grupo II, n = 6) e ratas tratadas com 200mg/kg/dia de silibinina (Grupo III, n = 6). Os animais receberam tratamento por via oral (gavage). Durante toda a prenhez, o consumo de ração e a ingestão de água, bem como o ganho de peso corporal foram avaliados. No dia 21 de prenhez as ratas foram anestesiadas A cesárea foi realizada no 21º dia, quando os recém-nascidos foram mortos e processados para análise das variações e/ou malformações. Resultados: os grupos controle e tratados não apresentaram diferenças significativas em relação aos parâmetros fetais, não se observando sinais de toxicidade materna com as diferentes concentrações de silibinina empregadas. Conclusão: O tratamento com silibinina não determinou efeitos deletérios na performance reprodutiva das ratas, mesmo quando utilizada em altas doses (200 mg/Kg/dia). / Abstract: Silibinin is a chemically defined flavonoid and the main active component of silymarin, a polyphenolic complex from fruits and seeds of Silybum marianum, which has anti-inflammatory, hepatoprotective and anticarcinogenic properties. Objective: The aim of the present study was to evaluate the dose-dependent effect of silibinin treatment on maternal reproductive performance and on abnormalities and/or fetal malformations. Methods: Pregnant Wistar rats were distributed in four experimental groups: control, not treated with silibinin (n=6), rats treated with silibinin 50mg/kg/day (Group I, n = 6), rats treated with silibinin 100mg/kg/day (Group II, n = 6) and rats treated with silibinin 200mg/kg/day (Group III, n = 6). Silibinin was administrated by gavage from day 0 to 20 of pregnancy. During the period of pregnancy food and water intake, as well as weight gain were evaluated. On day 21 of pregnancy, the rats were anesthetized and submitted to cesarean section to analyse maternal reproductive performance and fetal malformations. Results: The control and silibinin-treated groups did not show significant differences in relation to the fetal parameters evaluated and no maternal toxicity effects of silibinin were detected in the concentrations employed. Conclusion: Silibinin treatment did not determined deleterious effect on the maternal reproductive performance and fetal outcome even when employed in high dose (200 mg/Kg). / Mestre

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

Orientador: Renato Passini Junior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-27T11:36:41Z (GMT). No. of bitstreams: 1 Politano_GabrielTilli_D.pdf: 2041428 bytes, checksum: b671b24f9261d0181d5efd46b02c080f (MD5) Previous issue date: 2009 / Resumo: Introdução: A doença periodontal, afecção que pode acometer os tecidos de sustentação dos dentes, induz à liberação local e sistêmica de mediadores inflamatórios. A pré-eclâmpsia, caracterizada pela hipertensão e proteinúria em gestantes, também parece ter sua etiopatogenia parcialmente relacionada ao sistema imunológico, com aumento dos níveis plasmáticos de algumas citocinas. Objetivos: Esta pesquisa teve os seguintes objetivos: revisar a literatura quanto à associação entre doença periodontal e pré-eclâmpsia, analisar a influência do Fator de Necrose Tumoral-alfa (TNFa) e da Interleucina-6 (IL-6) na pré-eclâmpsia e avaliar a associação entre a doença periodontal e o desenvolvimento de pré-eclâmpsia, incluindo a análise das citocinas inflamatórias sistêmicas neste processo. Método: inicialmente procedeu-se à revisão de literatura sobre a relação entre doença periodontal e pré-eclâmpsia, seguida de estudo do tipo caso-controle, realizado em 58 gestantes com pré-eclâmpsia (casos) e 58 gestantes normotensas (controles). Foi realizada a coleta do sangue periférico para avaliação laboratorial da expressão sistêmica do RNA mensageiro (RNAm) das citocinas inflamatórias IL-6 e TNFa por meio do exame de Reação de Polimerização em Cadeia em Tempo Real (PCR em Tempo Real). Todas as gestantes tiveram o periodonto avaliado para se estabelecer presença ou ausência de periodontite. Para avaliação da homogeneidade entre os grupos foram utilizados o teste exato de Fisher, teste de Mann-Whitney, teste T de Student e teste qui-quadrado. O teste de Mann-Whitney também foi utilizado para comparação dos dados periodontais e de citocinas entre os grupos. Foram calculados odds ratio bruto e ajustado, através da regressão logística, para os fatores de exposição. A correlação entre todas as variáveis periodontais e a expressão das citocinas foi realizada por meio do teste de correlação de Spearman. O Risco Atribuível Populacional foi avaliado através da Fórmula de Levin. Resultados: Gestantes com pré-eclâmpsia apresentaram maior expressão do RNAm do TNFa, mas não diferiram do grupo-controle em relação à IL-6. Os dados evidenciaram associação entre a periodontite e a pré-eclâmpsia [odds ratio ajustado = 3,73 (IC 95% 1,32 a 10,58)]. Não houve correlação entre a periodontite e a expressão do RNAm das citocinas TNFa e IL-6. Conclusão: Observou-se associação clínica significativa entre a periodontite e a pré-eclâmpsia; no entanto, não se pôde confirmar a atuação das citocinas inflamatórias neste processo. Além disso, a maior expressão do TNFa em gestantes com pré-eclâmpsia reforça o envolvimento do sistema imunológico na doença / Abstract: Introduction: Periodontitis, an infectious disease affecting the supporting structures of the teeth, leads to local and systemic liberation of various inflammatory mediators. Preeclampsia, a disorder that occurs only during pregnancy and the postpartum period is characterized by high blood pressure and the presence of protein in the urine and also seems to have an immunological etiology, with increased plasma levels of some cytokines. Objectives: the aim of the present study was to explore existing literature surrounding the association between periodontitis and preeclampsia as well as to evaluate the influence of Tumor necrosis factor-alpha (TNFa) and Interleukin-6 (IL-6). This work also aimed to evaluate the association between periodontitis and preeclampsia development, including the analysis of systemic inflammatory cytokines. Methods: A review of the literature on the relationship between periodontal disease and preeclampsia was initially performed, followed by a case-control analysis of 116 pregnant women, 58 with preeclampsia (cases) and 58 normotense pregnant women (controls). Peripheral blood samples were also collected for laboratorial analysis of IL-6 and TNFa messenger RNA (mRNA) systemic expression, through realtime polymerase chain reaction (Real Time PCR). All participants underwent a clinical periodontal examination in order to assess the presence or absence of periodontal disease. Crude and adjusted odds ratio were calculated by multivariate logistic regression for exposure factors. Student's t-test, MannWhitney U-test, Fisher's exact test and Chi-Square test were used to ensure homogeneity of the groups. Mann-Whitney U-test was also used for intragroup comparison regarding level of cytokines and periodontal data. Correlations between all periodontal data and cytokines expression were determined by Spearman rank test. Population attributable risks were estimated using Levin's Formula. Results: the results showed increased TNFa mRNA expression from pre-eclamptic women as compared with normal pregnant women. There were no statistically significant differences in IL-6 between case and control groups. There was an association between periodontitis and preeclampsia [adjusted odds ratio = 3,73 (IC 95% 1,32 to 10,58)]. There was no correlation between periodontitis and IL-6 and TNFa messenger RNA (mRNA) expression. Conclusion: There was a significant clinical correlation between periodontitis and preeclampsia; however, an immunologic correlation via inflammatory cytokines could not be determined in our study. In addition, the high expression of TNF-a mRNA in pregnant women emphasizes the immunological mechanisms involved in periodontal disease / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

Publicación a texto completo no autorizada por el autor / Describe los principales hallazgos de monitoreo electrónico fetal según los criterios del Colegio Americano de Ginecología y Obstetricia en gestantes con preeclampsia atendidas en el Instituto Nacional Materno Perinatal de enero a diciembre del 2012. Estudio de tipo observacional, descriptivo, retrospectivo de corte transversal. Se trabaja con un total de 96 gestantes con diagnóstico de preeclampsia que acuden a la unidad de medicina fetal para un monitoreo electrónico en el Instituto Nacional Materno Perinatal durante el periodo de enero a diciembre del 2012. En la evaluación de los datos cardiotocográficos se tiene en cuenta a 123 trazados, considerándose que 20 de las 96 gestantes tuvieron más de 2 trazados. Los datos son procesados en una base de datos de excel y se analiza con el programa estadístico SPSS v.21. Para las variables cualitativas se estiman frecuencias absolutas y relativas, para las variables cuantitativas se estiman medidas de tendencia central (media y desviación estándar). La edad promedio de las gestantes evaluadas es de 26.85 años, siendo la mayoría gestantes adultas (60.4%). El 61.5% de las gestantes tienen como nivel de instrucción secundaria completa, siendo la mayoría amas de casa (84.4%), con estado civil conviviente (67.7%). La mayor parte de las gestantes proceden del servicio de emergencia (69.8%). El 68% de las gestantes presenta preeclampsia leve y el 32% presenta preeclampsia severa; el 59% de las gestantes son sometidas a Test Estresante y el 41% a Test No Estresante. El 40.7% de los Test No Estresantes corresponden a trazados de gestantes con preeclampsia leve y el 40.5% a trazados de gestantes con preeclampsia severa. El 59.3% de los trazados del Test Estresante son de gestantes con preeclampsia leve y el 59.5% con preeclampsia severa. Para los trazados del Test No Estresante en gestantes con preeclampsia leve, la línea de base es normal en 100%, la variabilidad es de 6-25 en el 57.1%, aceleraciones presentes en el 85.7%, desaceleraciones variables en el 14.3%, irritabilidad uterina en el 25.7%, obteniendo como resultado un feto activo reactivo (FAR) (85.7%); al respecto de la preeclampsia severa el 100% tiene una línea de base normal; el 66.7% presenta una variabilidad ≤5, el 20% presenta desaceleraciones variables, las contracciones en el 13.3% son regulares y en el 13.3% se evidencia irritabilidad uterina, resultando un feto activo reactivo (86.7%). Al respecto de los trazados del Test Estresante en preeclampsia leve, el 100% tiene una línea de base normal, el 58.8% una variabilidad ≤5, aceleraciones presentes en el 78.4%, desaceleraciones variables en el 13.7%, contracciones regulares en el 90.2%, obteniendo un trazado negativo reactivo (NR). En el caso de trazados de preeclampsia severa, el 100% presenta una línea de base normal, una variabilidad ≤5 (59.1%), aceleraciones presentes en el 81.8%, desaceleraciones prolongadas en el 4.5%, contracciones regulares en el 90.9%, obteniéndose como resultado un trazado negativo reactivo (NR). Concluye que los hallazgos del monitoreo electrónico fetal en gestantes con preeclampsia, monitorizadas en la unidad de medicina fetal del Instituto Nacional Materno Perinatal durante el periodo de enero a diciembre del 2012 según los criterios de la ACOG son en su mayoría normales: línea de base normal en el 100% de casos, aceleraciones presentes en el 82.1% y ausencia de desaceleraciones en el 83.7%, obteniéndose como resultado final un feto reactivo en el 86% de los Test No Estresante y negativo reactivo en el 73% de los Test Estresante. La alteración más frecuentemente encontrada es la variabilidad mínima (≤5) en el 54.5%. / Tesis

Preeclampsia (PE), a life threatening pregnancy-related disorder, is characterized mainly by new onset of hypertension and proteinuria after 20 weeks of gestation. Currently, PE cannot be predicted prior to onset of symptoms and there is no cure for the disease. There is a clear value in having biomarkers able, early in a pregnancy, to identify women at risk for PE so that proper treatment therapies could be developed. Although a number of serum candidate markers have been proposed to be altered in PE patients, their use is limited due to poor sensitivity and specificity. Therefore, there is ongoing need for better set of novel biomarkers predicting PE. Consequently, for my first project, we used a serum proteomic approach involving reversed phase capillary-liquid chromatography-electrospray ionization-quadrupole-time of flight mass spectrometry (cLC-ESI-QTOF). Our approach focuses on the less abundant (nM or lower), lower molecular weight peptides and lipids predicting PE. We got previously collected sera from pregnant women at 12–14 weeks gestation. There were 24 controls, having term uncomplicated pregnancies and 24 cases, which developed PE later in the same pregnancy. Many statistically significant serum PE biomarker candidates were found comparing cases and controls. In addition, multimarker combinations having high detection sensitivity and specificity (AUC >0.9) were developed using logistic regression analysis. For my second project, serum lipidomic analysis of sera from pregnant women was undertaken to determine if useful PE lipid biomarkers exist. A discovery study involving a shotgun lipidomic approach was performed using sera collected at 12-14 weeks of pregnancy from 27 controls with uncomplicated pregnancies and 29 cases that later developed PE. Lipids were extracted using organic solvent and analyzed by direct infusion into a time-of-flight mass spectrometer. Statistically significant lipid markers were found and reevaluated in a second confirmatory study having 43 controls and 37 PE cases. The initial study detected 45 potential PE markers. Of these, 23 markers continued to be statistically significant in the second confirmatory set. Several multi-marker panels with AUC >0.85 and high predictive values were developed from these markers. My third project also involved the above mentioned approach for detection of novel lipid biomarkers for Alzheimer's disease. Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of age-related dementia. Currently, there are no methods to detect Alzheimer's at an early stage when treatment therapies could be applied. Therefore, there is need for detection of panel of biomarkers for detecting patients at risk to AD at an early stage. In the initial discovery set, sera from 29 different stage AD cases and 32 controls were analyzed using direct infusion mass spectrometry (ESI-TOF). This study yielded 89 potential lipid biomarkers which were evaluated in another confirmation study. Of these, 35 markers continued to be statistically significant in the second confirmatory set. Using the confirmed markers, several multi-marker panels with AUC > 0.87 were developed for any stage AD cases vs controls. Multi-marker panels with AUCs > 0.90 were developed for each specific CDR vs controls, including the earliest stage of AD. These lipidomic biomarkers are likely to distinguish AD cases regardless of the stage from controls. In conclusion, we successfully detected, validated and identified low molecular weight novel biomarkers for PE and lipid biomarkers for AD.

Preeclampsia is a devastating disorder of pregnancy characterized by high blood pressure, proteinuria, headache, renal glomerular endotheliosis, multi-organ system failure, and fetal and maternal demise. As reviewed in Chapter I, not much is known about the pathogenesis of preeclampsia, contributing to a lack of biomarkers and treatments for the disease. In Chapter II, we review arginine vasopressin, a circulating neuropeptide hormone with important fluid balance and cardiovascular actions. Vasopressin binds to numerous receptors throughout the body to elicit its effects and is associated with various disease states. In Chapter III, we discuss evidence for vasopressin as an etiology of preeclampsia. Specifically, that vasopressin secretion is elevated very early in pregnancies affected by preeclampsia and infusion of vasopressin into pregnant C57BL/6J mice causes physiological features similar to those seen in preeclampsia. In Chapter IV, we show that vasopressin administration during mouse pregnancy models specific subtypes of preeclampsia through time- and receptor-specific mechanisms. The role of angiotensin 1a receptors on vasopressin-producing cells in fluid homeostasis is shown in Chapter V and their role in metabolism is depicted in Chapter VI. Overall, we conclude that vasopressin is an important mediator of features of preeclampsia and that angiotensin 1a receptors on vasopressin-producing cells are important for normal fluid homeostasis.

Objetivo: Determinar el valor predictivo del Índice Cerebro Placentario y del flujo anormal del Ductus Venoso de Aranzio, medido por velocimetría Doppler, en pacientes con preeclampsia, en relación a un resultado perinatal adverso. Materiales y métodos: Estudio prospectivo, no experimental, longitudinal, de tipo correlacional. Se realizaron exámenes ultrasonográficos Doppler para determinar el Índice Cerebro Placentario y el flujo anormal del Ductus Venoso de Aranzio, en los 7 días previos al parto, en 160 pacientes con diagnóstico de preeclampsia severa admitidas en la Unidad de Medicina Fetal y Diagnóstico Prenatal del Servicio de Obstetricia de Alto Riesgo del Hospital Guillermo Almenara Irigoyen – EsSalud. El resultado perinatal adverso fue definido por los siguientes parámetros: Cesárea por SFA, APGAR menor 7 a los 5´, Líquido amniótico meconial, Oligohidramnios, pH de la arteria umbilical menor 7,2, Admisión en UCI neonatal, RCIU. Se utilizó estadística descriptiva para la variable dependiente y estadística inferencial mediante el estadístico chi cuadrado (x²) y prueba exacta de Fisher, con un nivel de significancia de 0,05; confiabilidad del 95%. Además se calculó la sensibilidad, especificidad y valores predictivos positivo y negativo de la variable independiente. Conclusiones: Se ha demostrado que la alteración del Índice Cerebro Placentario y del Flujo del Ductus Venoso de Aranzio medido por flujometría Doppler fetal, detecta a más del 65% de los recién nacidos con resultado perinatal adverso e hipoxia fetal y se asocia a la ocurrencia del mismo. Además esta es una prueba predictiva, estadísticamente significativa, de RCIU y de oligohidramnios, en pacientes con preeclampsia severa. El presente estudio se realizó con un muestreo no aleatorio, por ende, este hecho de no aleatoriedad, pudiera plantear problemas de validez externa. / Objective: To ascertain the value of cerebral-placental ratio and the abnormal fluxo of Aranzio´s Ductus Venous and for identifying newborns with neonatal morbidity in pregnancies complicated by severe preeclampsia. Study Design: A longitudinal and correlational study of 160 patients with severe preeclampsia (PA > 160/110, proteinuria 3+) was performed Doppler study done by one operador within 7 days before delivery. An abnormal cerebral-placental ratio and abnormal resistance and pulsabilility index of ductus venous were used to identificate fetal asphixia (cardiac insuficiency). The results belong 5 percentile were considered abnormal. These results were matched with perinatal results considered as abnormal. Results: Maternal characteristic were: age 33, parity 1, primigravid 45%, prenatal care 85%, gestational age at enrollment 35,1 weeks. The probability of detection IUGR is 65% and oligohydramnios 61,2%. Conclusion: The cerebral-placental ratio and abnormal fluxo of Aranzio´s Ductus venous identifies 65 % or more of the newborns with severe neonatal morbidity in pregnancies with severe preeclampsia. / Tesis

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

Placental dysfunction is implicated in the pathogenesis of preeclampsia. Chemical signals between the placenta and maternal circulation are a suspect cause of endothelial dysfunction and maternal hypertension. This study examined select lipid mediators of inflammation produced by the placenta. Patients were recruited from Virginia Commonwealth University’s pregnancy clinics and placentas were collected at delivery. Forty-eight-hour explant cultures of villous placental tissue were used to model lipid production. Electrospray ionization mass spectrometry was used to quantify concentrations of free lipids in the culture media. Bicinchoninic acid assays were performed to quantify protein in each culture for normalization of lipid data. After analysis, it was found that severity of preeclampsia was correlated with a unique lipid profile. Pro-inflammatory hydroxyeicosatetraenoic acids and sphingolipids were elevated. Aspirin usage in patients who developed preeclampsia was found to attenuate accumulation of isoprostane oxidative stress markers and thromboxane production while preserving omega-3-fatty acid and increasing prostacyclin levels.

Preeclampsia is a leading cause of maternal and infant morbidity and mortality worldwide. For the first aim, a systematic literature review and meta-analysis was performed to examine the associations between maternal lipid concentrations during pregnancy (HDL-C, LDL-C, non-HDL-C, total cholesterol, and triglycerides) with subsequent risk of preeclampsia. Data from the Study of Pregnancy-induced Hypertension in Iowa, a population-based, case control study of preeclampsia and gestational hypertension, was used to address the other two aims: 1) elucidate the independent contribution of physical activity, an important modifier of dyslipidemia, on the risk of preeclampsia, and 2) to evaluate the association between the genetic susceptibility for dyslipidemia and the risk of preeclampsia. Published reports examining lipid levels during pregnancy and preeclampsia have been inconsistent. Meta-analyses demonstrated that preeclampsia was associated with elevated total cholesterol, non-HDL-C, and triglyceride levels, regardless of gestational age at time of blood draw, and lower levels of HDL-C in the third trimester. A marginal association was also found with LDL-C levels. Statistical heterogeneity was detected in all analyses. Physical activity has been hypothesized to reduce the risk of preeclampsia, but previous studies have had a range of limitations resulting in mostly suggestive, though nonsignificant findings. After adjustments, increasing levels of LTPA (trend, p=0.02) and increasing amounts of time spent active each day (trend, p=0.03) were significantly associated with a reduced risks of preeclampsia (trend, p=0.02). Increasing amounts of time spent sitting per day was marginally associated with the risk of preeclampsia (trend; p=0.10), and those women who were active an average of more than 8.25 hours per day had the most significantly reduced risk of preeclampsia (adjusted OR 0.58, 95% CI 0.36, 0.95). In examining the effects of a woman's genetic susceptibility to dyslipidemia as a risk factor for preeclampsia, we found that the more risk alleles a woman has for dyslipidemic levels of HDL-C, the greater her risk for developing preeclampsia. While this relationship was of marginal statistical significance, these results are suggestive of a relationship that may help elucidate the pathogenesis of preeclampsia. Our findings demonstrate the contribution of maternal lipid concentrations during pregnancy on preeclampsia risk, and suggest a behavioral modification that could help counter that increased risk. Additionally, implications of HDL-C genetics in preeclampsia risk identify potential genetic and biologic pathways to be explored in the pathogenesis of preeclampsia.