Atividade de monócitos em gestantes normais e com pré-eclâmpsia

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia

Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms. We examined how three eNOS polymorphisms [T-786C, rs2070744; Glu298Asp, rs1799983; 27 bp variable number of tandem repeats (VNTR) in intron 4] affect plasma nitrite concentrations in 205 pregnant women [107 healthy pregnant (HP) and 98 PE]. Genotypes were determined and eNOS haplotypes were inferred using the PHASE 2.1 program. The plasma nitrite concentrations were determined using an ozone-based chemiluminescence assay. The Glu298Asp polymorphism had no effects on the plasma nitrite concentrations. Higher nitrite levels were found in HP women with the CC versus TT genotype for the T-786C polymorphism (277.9 +/- 19.5 versus 140.6 +/- 8.2 nM; P < 0.05). Lower nitrite levels were found in healthy women with the 4a4a versus 4b4b genotype for the VNTR polymorphism (95.1 +/- 3.3 versus 216.1 +/- 16.8 nM; P < 0.05). No effects of genotypes were found in PE women (all P > 0.05). The `C Glu b` haplotype was more frequent in the HP group than in the PE group (20 versus 5; P = 0.0044). This haplotype was associated with higher nitrite concentrations than the other haplotypes in healthy pregnancies (P < 0.05). No differences in nitrite concentrations were found among PE women with different eNOS haplotypes (P > 0.05). These findings indicate that eNOS polymorphisms affect endogenous NO formation in normal pregnancy, but not in PE, and that the `C Glu b` haplotype may protect against the development of PE by increasing endogenous NO formation.

Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension

Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions are associated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to pre-eclampsia (PE), and no studies on how they affect susceptibility to gestational hypertension (GH), we compared VEGF genotype and haplotype distributions in normotensive and hypertensive pregnancies. Genotypes and haplotypes for VEGF polymorphisms (C-2578A, G-1154A and G-634C) were determined in 303 pregnant women (108 healthy pregnant, HP; 101 with GH and 94 with PE). When white and non-white pregnant women were considered together, no significant differences were found in the distributions of VEGF genotypes or haplotypes (P > 0.05) in the three groups. However, with only white subjects, significant differences were found in genotypes distributions for two (C-2578A and G-634C) VEGF polymorphisms (both P < 0.05) between the HP and the PE groups. Importantly, the haplotype including the variants C-2578, G-1154 and C-634, which is associated with higher VEGF gene expression, was less common in the PE group compared with the HP group (4% versus 16%; P = 0.0047). However, we found no significant differences in VEGF haplotypes distributions when the HP and GH groups were compared (P > 0.05). These findings suggest a protective effect for the `C-2578, G-1154 and C-634` haplotype against the development of PE, but no major effects of VEGF gene variants on susceptibility to GH.

Aspectos imunológicos e parasitológicos em Biomphalaria tenagophila infectadas por Schistosoma mansoni e outros Digenea

Estudou-se o comportamento de amebócitos de Biomphalaria tenagophila infectadas por Schistosoma mansoni, por outros Digenea e a resistência à superinfecção, presente em infecções mistas. Foi verificada a atividade fagocitária dos amebócitos, o número destas células circulantes, a reação amebocitária nos tecidos, o perfil eletroforético da hemolinfa, além da reação de imunodifusão. Concluiu-se que moluscos infectados por outros Digenea apresentam resistência à superinfecção por S. mansoni, sendo que os amebócitos parecem não ter participação direta na destruição dos esporocistos de S. mansoni nesta eventualidade. Nos moluscos infectados observou-se maior número de amebócitos circulantes e aumento de capacidade fagocitária destas células.

Aspectos imunológicos do sistema enzimático fenoloxidase de Schistosoma mansoni

O sistema enzimático fenoloxidase (EC 1.10.3.1, EC 1.10.3.2) está amplamente distribuido entre os seres vivos, tendo sido descrito em diferentes espécies do reino animal e vegetal. Apesar de desempenhar um papel fundamental na formação da cápsula ou parede dos ovos de trematódeos, o sistema enzimático fenoloxidase (PO) tem sido pouco estudado nesses organismos. No presente trabalho são apresentados os resultados iniciais de imunizações de coelhos contra PO de fêmeas adultas de S. mansoni e tirosinase de cogumelo (Sigma). As análises imunológicas, realizadas através de imunodifusão dupla (teste de Ouchterlony) e imunoeletroforese, revelaram identidade imunitária parcial entre a PO de machos e fêmeas. Não se observou reação cruzada entre os antissoros de coelhos imunizados contra PO e aqueles com tirosinase, indicando que, embora os sítios catalíticos de ambas as enzimas devam ser semelhantes, já que atuam sobre os mesmos substratos, os determinantes antigênicos devem ser diferentes. Os resultados descritos no presente trabalho representam um primeiro passo no sentido da purificação das isoenzimas da fenoloxidase e sua posterior utilização ao estudo dos mecanismos moleculares envolvidos na esclerotização da parede dos ovos de S. mansoni.

Aspectos imunológicos da Leishmaniose Cutis Difusa

Um caso de Leishmaniose Cutis Difusa é estudado quanto aos seus aspectos imunológicos. A imunidade celular foi investigada com testes intradérmicos, sensibilização artificia! do DNCB e dosagem de fator de inibição do macrófago (MIF). Embora alguns antígenos injetados tivessem dado reação positiva, a leishmanina foi não reatora evidenciando uma anergia específica. As imunoglobulinas G e M estavam elevadas. 0 encontro de anticorpos circulantes por alguns autores associando ao fato de que o complemento C3 era baixo em nosso paciente, levou-nos a considerar o consumo deste que fixado a complexos Ag-Ac circulantes poderiam explicar os surtos de febre e artralgias. Por fim são considerados os pontos de vista de autores diferentes em relação ao fato de que a LCD seria causada por espécie diferente de leishmânia, ou por defeito imunológico do paciente, destacando-se o trabalho de Convit³ em favor desta útlima hipótese.

Panencefalite subaguda esclerosante: correlação entre aspectos imunológicos e histopatológicos

Foi realizado um estudo clínico, laboratorial, eletroencefalográfico, sorológico e virológico em 4 pacientes com o diagnóstico clínico de "panencefalite subaguda esclerosante". Em todos constatou-se uma elevada concentração de anticorpos contra sarampo, tanto no líquido céfalo-raquidiano como no soro sangüíneo, sendo que em 3 pacientes a concentração de anticorpos era mais elevada no líquido céfalo-raquidiano. Em dois destes pacientes foram feitas biópsias cerebrais, que evidenciaram um processo meningo-encefalítico crônico, com focos de neuroniofagia esparsos e infiltrados inflamatórios perivasculares de natureza linfoplasmocitária. Ao mesmo tempo fez-se uma revisão de 18 casos desta enfermidade, já publicados, agora no sentido de estudar mais detidamente a natureza da infiltração inflamatória meníngea e perivascular. O aspecto histopatológico resumia-se em infiltração linfoplasmocitária meníngea esparsa, contrastando com densos infiltrados inflamatórios perivasculares também linfoplasmocitários, muitas vezes com grande riqueza em "corpos de Russell". Em vista destes achados sugere-se a possibilidade de que os anticorpos contra sarampo, encontrados em elevada concentração no líquido céfalo-raquidiano destes pacientes, sejam produzidos nos infiltrados perivasculares do próprio tecido nervoso.

Aspectos imunológicos da infecção de seis linhagens isogênicas de camundongos por três diferentes cepas do Trypanosoma cruzi

Foram avaliados aspectos da imunidade humoral e celular em seis linhagens de camundongos isogênicos (BALB/c, B-10, C3H, A/J, AKR e DBA) infectados por três cepas do Trypanosoma cuzi, representantes dos três tipos de cepas da classificação de Andrade (cepas Peruana, 21SF e Colombiana). A imunidade celular, avaliada pelo teste de hipersensibilidade cutânea tardia contra antigenos do parasita, estava suprimida. A avaliação dos níveis de imunoglobulinas (imunodifusão radial), mostrou queda precose de IgG1 e elevação de IgM em praticamente todas as linhagens infectadas por qualquer das cepas estudadas. A elevação de IgG2a e/ou IgG2b foi mais intensa nas linhagens mais resistentes. Os níveis de anticorpos anti-T, cruzi (Imunofluorescência indireta e ELISA) não se correlacionam com a sobrevida dos animais. Apesar de diferenças entre as linhagens observou-se uma regularidade na resposta do hospedeiro e a manutenção dos padrões biológicos que caracterizam os tipos de cepa.

Comprender la experiencia de la mujer ingresada con pre-eclampsia y eclampsia

Introducción: La preeclampsia/eclampsia es una enfermedad del embarazo que puede producir cambios en el estado emocional de la mujer por su prolongado ingreso hospitalario. Objetivo: Conocer las experiencias vividas por las mujeres con preeclampsia/eclampsia durante el ingreso hospitalario. Los objetivos que se tendrán en cuenta serán conocer cómo se modifica el rol propio dentro de la organización familiar, conocer cómo impacta su ingreso respecto a suestado emocional, conocer cómo les afecta la estructura de la unidad a su estado emocional y conocer qué necesidades y/o cuidados terapéuticos reciben respeto al equipo sanitario. Ámbito: El estudio se realizará en el Hospital de la Vall d’ Hebrón de Barcelona. Metodología: Estudio fenomenológico. La muestra se escogerá intencionadamente que cumplirá con los criterios de inclusión (mujeres ingresadas por preeclampsia/eclampsia en launidad de materno infantil de la Vall d’ Hebrón de Barcelona), y se terminará hasta llegar al nivel de saturación teórico. Los datos se recogerán a través de entrevistas semi-estructuradas y de la observación participante. Consideraciones finales: Dada la baja incidencia que existe tanto a nivel nacional como internacional en estudios de este tipo, un estudio cualitativo que ayude a conocer las experiencias de las mujeres ingresadas por preeclampsia podría ayudar a mejorar la calidad y práctica asistencial enfermera.

Correlación de la prueba sin estrés en pacientes con embarazo complicado con pre-eclampsia y sus resultados perinatales [por] Imelda Balderas López

Tesis (Especialidad en Ginecología y Obstetricia). U. A. N. L.

Therapeutic patents for the treatment of pre-eclampsia

Pre-eclampsia (PE) is a pregnancy-specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths. In its mild form, PE most commonly presents with the features of maternal hypertension and proteinuria but can swiftly and unpredictably become severe with many extensive and life-threatening complications. The diverse symptoms of PE have made it a difficult disease not only to define, but also to identify a causative agent for the symptoms. It has therefore proved difficult to develop specific drugs that can be used to manage the condition. This review examines the patent literature to reveal current findings that exhibit the potential to target the effects of PE with the aim of either preventing or altering the course of this life-threatening disease of pregnancy.

Syncytiotrophoblast extracellular vesicles from pre-eclampsia placentas differentially affect platelet function

Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition.

Tumor necrosis factor-alpha in gestation and puerperium of women with gestational hypertension and pre-eclampsia

Problem High plasma levels of tumor necrosis factor-alpha (TNF-alpha) in pregnant women have been associated with the pathogenesis of pre-eclampsia (PE). This study evaluated TNF-alpha plasma levels and monocyte production in gestational hypertension (GH) and PE during gestation and at puerperium.Method of study This study included 128 women, of whom 20 were non-pregnant (NP) normotensive (NT), and 108 were pregnant: 36 NT, 27 with GH, and 45 with PE. Peripheral blood plasma was used for TNF-alpha and uric acid determination. TNF-alpha was determined in plasma and lipopolysaccharide (LPS)-stimulated and non-stimulated monocyte supernatants by L929 bioassay.Results Tumor necrosis factor-alpha and uric acid plasma levels were higher in PE than in GH pregnancies. In both hypertensive groups, these parameters positively correlated and were significantly more elevated than in NT and NP women. TNF-alpha plasma levels and monocyte production were higher in hypertensive than in NT women during gestation, and significantly decreased at puerperium. Although decreased, TNF-alpha release in LPS-stimulated PE monocytes, was still significantly higher than in the other pregnant groups.Conclusion In vivo monocyte activation in GH and PE pregnant women was characterized by in vitro TNF-alpha production. The fact that higher circulating concentrations of TNF-alpha and uric acid were observed in PE than in GH suggests an association with disease severity.

Polymorphisms of the adiponectin gene in gestational hypertension and pre-eclampsia

Adiponectin is a hormone involved in energy homeostasis by regulating glucose and lipid metabolism. In addition, the adiponectin gene (ADIPOQ) has polymorphisms that can modulate the circulating concentration of adiponectin. Abnormal adiponectin levels have been associated with pre-eclampsia (PE); however, the influence of genetic polymorphisms on the development of hypertensive disorders of pregnancy is unclear. The aim of this study was to examine whether ADIPOQ polymorphisms are associated with gestational hypertension (GH) and/or PE. We studied 401 pregnant women: 161 healthy pregnant (HP), 113 pregnant with GH and 127 pregnant with PE. ADIPOQ polymorphisms -11391G>A (rs17300539), -11377C>G (rs266729), 45T>G (rs2241766) and 276G>T (rs1501299) were genotyped by allelic discrimination assays using real-time PCR. Haplotypes were inferred using the PHASE 2.1 program. We observed that the genotypic frequencies of the -11377C>G polymorphism were different in PE compared with HP (P<0.0125), with the CT genotype being more commonly found in PE patients than in HP women (P<0.0125). However, allelic frequencies of this single-nucleotide polymorphism were similar between PE and HP (P>0.0125). No difference was observed when GH and HP groups were compared (both P>0.0125). In addition, we found no difference in genotype or allele distributions for the -11391G>A, 45T>G and 276G>T polymorphisms when we compared GH or PE with HP (all P>0.0125). In conclusion, we found a modest association between the CG genotype of the -11377C>G polymorphism and PE.Journal of Human Hypertension advance online publication, 27 June 2013; doi:10.1038/jhh.2013.53.