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.

Genes candidatos de suscetibilidade a pré-eclampsia: estudo de associação

Preeclampsia is a multifactorial disease of unknown etiology that features with wide clinical symptoms, ranging from mild preeclampsia to severe forms, as eclampsia and HELLP syndrome. As a complex disease, preeclampsia is also influenced by genetic and environmental factors. Aiming to identify preeclampsia susceptibility genes, we genotyped a total of 22 genetic markers (single nucleotides polymorphisms SNPs) distributed in six candidates genes (ACVR2A, FLT1, ERAP1, ERAP2, LNPEP e CRHBP). By a case-control approach, the genotypic frequencies were compared between normotensive (control group) and preeclamptic women. The case s group was classified according to the disease clinical form in: preeclampsia, eclampsia and HELLP syndrome. As results we found the following genetic association: 1) ACVR2A and preeclampsia; 2) FLT1 and severe preeclampsia; 3) ERAP1 and eclampsia; 4) FLT1 and HELLP syndrome. When stratifying preeclampsia group according to symptoms severity (mild and severe preeclampsia) or according to the time of onset (early and late preeclampsia), it was detected that early preeclampsia is strongly associated to risk preeclampsia, eclampsia and HELLP syndrome have different genetic bases, although FLT1 gene seems to be involved in preeclampsia and HELLP syndrome pathophisiology

O cuidado em saúde no ciclo gravídico-puerperal sob a perspectiva de usuárias de serviços públicos

O objetivo do trabalho foi apreender as representações sociais de puérperas sobre o cuidado em saúde no período pré-natal, no parto e no puerpério, em um contexto regional de serviços públicos de saúde do interior paulista. Seguindo a abordagem de pesquisa qualitativa, os dados foram colhidos por meio de entrevistas semi-estruturadas, realizadas em 2004, e organizados segundo o método do Discurso do Sujeito Coletivo, tendo o Programa de Humanização do Pré-natal e Nascimento (PHPN) como referencial teórico para discussão dos resultados. A perspectiva das puérperas sobre o cuidado em saúde no ciclo gravídico-puerperal evidenciou a importância das relações interpessoais, a essencialidade da qualidade técnica do atendimento e a propriedade da percepção de que o sujeito da atenção é a mulher e, como tal, dela deve participar efetivamente. Conclui-se que as diretrizes do PHPN devem ser incorporadas de forma mais ampla nas práticas de saúde voltadas à mulher, recomendando-se a adoção de indicadores específicos para avaliação das dimensões do cuidado evidenciadas por este estudo.

Feelings and Perceptions of Women in the Pregnancy-Puerperal Cycle Who Survived Severe Maternal Morbidity

Objetivou-se compreender a experiência relativa à morbidade materna grave, a partir de um grupo de mulheres que vivenciou esse problema. Adotaram-se os preceitos metodológicos da pesquisa qualitativa, sendo o Discurso do Sujeito Coletivo o referencial metodológico. Foram entrevistadas 16 mulheres que vivenciaram a morbidade materna grave. Os resultados foram discutidos a partir de quatro temas: descrevendo o desejo e o planejamento para ter um filho, percebendo seu problema de saúde, sua influência na gestação e para o concepto, passando pelo choque inicial no pós-parto e experienciando a situação de risco: desejos, frustrações e superação. Espera-se que este trabalho possa contribuir para qualificar a assistência de enfermagem, especialmente para reconhecer a diversidade e amplitude de necessidades que mulheres apresentam em situações de morbidade grave, durante o ciclo gravídico puerperal.

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.

Avaliação da assistência pré-natal e puerperal desenvolvidas em região do interior do Estado de São Paulo em 2005

Objectives: to evaluate the structure and process of the prenatal and puerperal care given by Direção Regional de Saúde (DIR) XI, at the city of Botucatu, State of São Paulo, Brazil. Methods: an evaluation of resources and activities developed during prenatal and puerperal care in twenty municipalities comprising DIR XI which had adhered the Prenatal and Birth Humanization Program until 2003. Interviews with city managers and analysis of 385 sampled patient charts taking into account recommendations by the Health Department. Results: structure analysis showed that caregiving was centered on medical work; basic equipment and instruments were available; 85.2% of patients began prenatal care with up to 120 days of pregnancy, and 75.9% had at least six prenatal consultations. The active search for absentees and strategies for early prenatal care initiation were observed in 30% and 50% of the municipalities, respectively. Process indicators showed that 3.6% of women had six prenatal consultations, one puerperal consultation, all basic exams and tetanus immunization. Recording of gestational age, arterial blood pressure and weight was of approximately 90%; 58.7% of the women underwent childbirth review and 31.5% were vaccinated. Conclusions: the performance of the set of activities is a challenge to prenatal care at DIR XI.

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.

Sentimentos e percepções de mulheres no ciclo gravídico-puerperal que sobreviveram à morbidade materna grave

Pós-graduação em Enfermagem (mestrado profissional) - FMB

O estado puerperal e suas interseções com a bioética

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Bioimpedância na gravidez: resistência e reactância de gestantes com pré-eclampsia

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O estado puerperal e suas interseções com a bioética

Lillian Ponchio e Silva discute aqui, com rigor e veemência, alguns pontos nevrálgicos do debate relativo ao altamente polêmico delito do infanticídio. O trabalho utiliza como fundamento a constatação de que a Bioética principalista não leva em conta os conflitos presentes no contexto social de países com grandes desigualdades. Esta última ciência pressupõe um sujeito livre de qualquer tipo de opressão e, assim, torna o infanticídio um crime essencialmente moral, sem levar em conta suas condicionantes sociais. Ao considerar somente algumas vozes e interesses, portanto, a Bioética principalista deixa à margem da pauta de discussão os indivíduos e grupos tradicionalmente oprimidos e vulneráveis. Para a autora, é preciso buscar uma maneira mais adequada de tratar o infanticídio e, ainda, tentar avançar na discussão de algumas questões específicas, como a análise do estado puerperal (expressão extremamente ambígua e muito contestada pelos médicos) e a tutela do bem jurídico no infanticídio, além do tratamento dispensado à mulher nessa situação.

Monocytes from Pregnant Women with Pre-Eclampsia are Polarized to a M1 Phenotype

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)