Revisão da leucina aminopeptidase no trabalho de parto pré-termo e na pré-eclampsia / Revision of the leucine aminopeptidase in preterm labor and in preeclampsia

Realizou-se um levantamento bibliográfico, com artigos de revisão, analisando e discutindo os trabalhos publicados sobre os efeitos da leucina aminopeptidase e aminopeptidase A no trabalho de parto pré-termo e na pré-eclampsia. A proposta deste trabalho sobre o tema é que grande parte das questões de saúde materna parece pueril, principalmente quanto ao atendimento voltado para os cuidados maternos, no qual, a cada 20minutos, morre uma mulher em decorrência de parto, no mundo todo. Por isso, tais doenças poderão receber mais atenção do que outras. Esse fato fez com que houvesse certa preocupação com o índice de natalidade e morbidade materna, bem como morbidade e mortalidade perinatal. Portanto, abordou-se sobre sua biologia geral, fisiologia de reprodução, síntese de evolução genética, habitação, alimentação, manejo, dor e eutanásia, técnicas de riscos desenvolvidos na experimentação animal, estudos de experimentos farmacológicos e toxicológicos observados dentro dos artigos de revisão. Embora tendências atuais preconizem a utilização de métodos alternativos (estudo in vitro), os modelos animais, como as ratas, apresentam como principal vantagem o fornecimento de informações sobre o organismo como um todo, fato que não é obtido com outros métodos, o que ainda possibilita o seu emprego em pesquisas científicas.

We have carried out a literature review, with review articles, analyzing and discussing the works that have already been published on the effects of leucine aminopeptidade and aminopeptidase A in pre-term labor and preeclampsia. The proposal of this work on the subject is that most of the issues of maternal health seems childish, especially for service oriented maternity care, where, every 20 minutes, a woman dies due to childbirth, worldwide. Therefore, such diseases may receive more attention than others. This led to worry about the birth rate and maternal morbidity and perinatal morbidity and mortality. Therefore, it was addressed their general biology, physiology of reproduction, synthesis of evolution, genetics, housing, feeding, pain and euthanasia techniques developed for animal experimentation risks, studies of pharmacological and toxicological experiments observed within the review articles. Although current trends have preconized the use of alternative methods (in vitro study), animal models, such as rats, have as main advantage the provision of information on the organism as a whole, a fact that is not achieved with other methods, which also allows its use in scientific research.

Insulin stimulation of Akt/PKB phosphorylation in the placenta of preeclampsia patients / Estimulação com insulina da fosforilação da Akt/PKB em placenta de pacientes com pré-eclâmpsia

CONTEXT AND OBJECTIVE: Preeclampsia is a multi-systemic disease and one of the most frequent severe health problems during pregnancy. Binding of insulin triggers phosphorylation and activates cytoplasmic substrates such as phosphatidylinositol 3 kinase (PI3K). Phosphorylation of membrane phosphoinositide 2 (PIP2) to phosphoinositide 3 (PIP3) by PI3K starts Akt/PKB activation. Defects in phosphorylation of the insulin receptor and its substrates have an important role in insulin resistance. Studies have shown that insulin resistance is associated with preeclampsia and its pathophysiology. The aim here was to investigate insulin stimulation of the Akt/PKB pathway in the placenta, in normal and preeclampsia parturients. DESIGN AND SETTING: Cross-sectional study in a tertiary public university hospital. METHODS: Placentas were collected from 12 normal and 12 preeclampsia patients. These were stimulated and analyzed using Western blot to quantify the Akt/PKB phosphorylation. RESULTS: The insulin stimulation was confirmed through comparing the stimulated group (1.14 ± 0.10) with the non-stimulated group (0.91 ± 0.08; P < 0.001). The phosphorylation of Akt/PKB did not differ between the placenta of the normal patients (1.26 ± 0.16) and those of the preeclampsia patients (1.01 ± 0.11; P = 0.237). CONCLUSIONS: In vitro insulin stimulation of the human placenta has been well established. There was no difference in Akt/PKB phosphorylation, after stimulation with insulin, between placentas of normal and preeclampsia patients. Nevertheless, it cannot be ruled out that the Akt/PKB signaling pathway may have a role in the pathophysiology of preeclampsia, since the substrates of Akt/PKB still need to be investigated.

CONTEXTO E OBJETIVO: Pré-eclâmpsia (PE) é uma doença multissistêmica das mais frequentes e graves durante a gestação. A ligação da insulina inicia a fosforilação e ativação de substratos citoplasmáticos, tais como fosfatidil-inositol 3 quinase (PI3K). A fosforilação do fosfoinositol 2 (PIP2) da membrana em fosfoinosiltol 3 (PIP3) pela PI3K inicia a ativação da Akt/PKB. Defeitos na fosforilação do receptor de insulina e seus substratos têm papel importante na resistência à insulina. Estudos demonstraram que resistência à insulina está associada com pré-eclâmpsia e sua patofisiologia. O objetivo foi investigar a via de estimulação com insulina da Akt/PKB em placenta de parturientes normais e com pré-eclampsia. TIPO DE ESTUDO E LOCAL: Estudo do tipo transversal em um hospital universitário público de nível terciário. MÉTODOS: Vinte e quatro placentas (12 normais, 12 com PE) foram coletadas, estimuladas e analisadas por Western blot para quantificar a fosforilação da Akt/PKB. RESULTADOS: A estimulação com insulina foi confirmada comparando os grupos estimulados (1,14 ± 0,10) e não estimulados (0.91 ± 0.08; P < 0.001). A fosforilação de Akt/PKB não foi diferente na placenta de pacientes normais (1,26 ± 0,16) e com PE (1,01 ± 0,11; P = 0,237). CONCLUSÕES: A estimulação in vitro da placenta humana com insulina foi bem estabelecida. Não houve diferença na fosforilação da Akt/PKB após estimulação em placentas de pacientes normais e PE. Contudo, não é possível descartar a participação desta via de sinalização na patofisiologia da PE, uma vez que os substratos da Akt/PKB ainda precisam ser investigados.

Endothelial nitric oxide synthase traffic inducer in the umbilical vessels of the patients with pre-eclampsia / 华中科技大学学报（医学）（英德文版）

The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) was examined in the umbilical vessels of the patients with pre-eclampsia (PE) to explore its possible role in the pathogenesis of PE. The NOSTRIN mRNA in umbilical tissues was determined by RT-PCR. The eNOS activity in umbilical vessels was spectrophotometrically detected. NO2-/NO3-, the stable metabolic end products of NO, was measured by using nitrate reductase. RT-PCR showed that the expression level of NOSTRIN was significantly higher in women with PE than in the normal group (P<0.01). The activity of eNOS was significantly decreased in PE group [(12.83+/-3.61) U/mg] than in normal group [(21.72+/-3.83) U/mg] (P<0.01). The level of NO2-/NO3- in PE patients (27.53+/-7.48) micromol/mg was significantly lower than that of normal group (54.27+/-9.53) micromol/mg (P<0.01). The significant negative correlation existed between the expression of NOSTRIN and the activity of eNOS in umbilical vessels of women with PE (r=-0.58, P<0.01). It was concluded that the level of NOSTRIN expression was increased in umbilical vessel of women with PE, indicating that it may be involved in the pathogenesis of PE.

Los niveles séricos de adenosin deaminasa y ácido úrico se correlacionan en pacientes gestantes con trastornos hipertensivos / Serum levels correlations of the enzyme adenosine deaminase (ADA) and uric acid in pregnant with hypertensive disorders

Objetivo: Evaluar los niveles séricos de la enzima adenosin-deaminasa (ADA) en pacientes gestantes normales y en pacientes con trastornos hipertensivos del embarazo, para determinar su relación con la gravedad del trastorno hipertensivo y con los niveles séricos de marcadores bioquímicos. Método: Se evaluaron pacientes con preeclampsia leve, preeclampsia grave, hipertensión gestacional y embarazadas sanas (n=10 por cada grupo). Se determinaron los niveles de ADA, ácido úrico, creatinina, amonio y enzimas hepáticas. Resultados: Se detectó una elevación en los niveles séricos de ADA en pacientes con preeclampsia y con hipertensión gestacional, en comparación con aquellas que cursaron con un embarazo normal. Los niveles ADA se correlacionaron positivamente con los niveles de ácido úrico y creatinina, más no con la severidad clínica. A su vez los niveles de ácido úrico se asociaron con la creatinina sérica y con la severidad clínica de los trastornos hipertensivos. Se encontró un incremento en los niveles de amonio en los pacientes con preeclampsia, el cual no se correlacionó con los otros marcadores bioquímicos, mientras que los niveles de TGO, TGP y LDH se encontraron significativamente elevados en la preeclampsia grave. Conclusión: Este estudio permite relacionar la actividad de ADA con los trastornos hipertensivos del embarazo, los niveles elevados de amonio con la preeclampsia y los niveles de ácido úrico, TGO, TGP y LDH con la severidad de los trastornos hipertensivos.

Objective: To evaluate serum levels of the enzyme adenosine deaminase (ADA) in normal pregnant and patients with hypertensive disorders induced by pregnancy, in order to determine their relationship with the severity of the hypertensive disorder and with serum biochemical markers. Method: We evaluated patients with mild preeclampsia, severe preeclampsia, gestational hypertension and healthy pregnancy (n=10 per group). We determined the serum levels of ADA, uric acid, creatinine, ammonia and liver enzymes. Results: In patients with preeclampsia and gestational hypertension we detected a rise in serum ADA as compared with those who had undergone a normal pregnancy. ADA levels were positively correlated with uric acid and creatinine serum levels, but not with clinical severity. Uric acid levels were associated with serum creatinine and the clinical severity of hypertensive disorders. We also found an increase in ammonia levels in patients with preeclampsia, which did not correlate with other biochemical markers, while the levels of SGOT, SGPT, and LDH were significantly elevated in severe preeclampsia. Conclusion: This study establishes a link between the activity of ADA with hypertensive disorders of pregnancy, high levels of ammonium with preeclampsia and uric acid, SGOT, SGPT and LDH levels with the severity of hypertensive disorders.

Some histochemical changes in the placentae of preeclampsia

The placenta has been implicated in the pathophysiology of preeclampsia. Preeclampsia is more common in multifetal gestations which have an increased placental mass compared to singleton pregnancies. Detecting the effects of preeclampsia on the availability of enzymes in the full term placenta. Two groups of placentae were taken from full term pregnant women immediately after labour, each consisting of ten placentae. The first group are placentae obtained from women having an uneventful pregnancy with no history of disease or complication [as a control group] while the second group consists of placentae obtained from women with a history of preeclampsia. The materials were obtained from Al-Batool and Al-Khansaa Teaching Hospitals in Mosul, between February and July [2006]. Significant histochemical changes were detected in the placentae of the second group when compared with those from the first group, such changes result from syncytial damage and destruction affecting the preeclamptic placentae, leading to the loss of alkaline phosphatase enzyme with an increase in the amount of the degenerating acid phosphatase enzyme

Síndrome Hellp no asociado a hipertensión arterial: a propósito de un caso en el Hospital Patrocinio Peñuela Ruíz / Syndrome hellpp not associated to arterial hypertension: concerning a case in the Hospital Patrocinio Peñuela Ruíz

El síndrome HELLP se presenta usualmente en pacientes con preclampsia; sin embargo, puede presentarse en ausencia de hipertensión arterial en el 20 por ciento de los casos. Se presenta caso de primigesta de 34 años, 35 semanas de gestación sin antecedentes importantes y control prenatal normal, quien acusa epigastralgia de aparición súbita, encontrándose cifras tensionales de 120/70 mmHG. Presenta cuadro convulsivo seguido de hipertensión arterial transitoria; se realiza cesárea segmentaria con post-operatorio inmediato en malas condiciones generales y cifras tensionales normales. Hallazgos de laboratorio que orientan hacia Síndrome HELLP clase 2 con insuficiencia renal aguda. En Unidad de Cuidados Intensivos desarrolla Síndrome de Dificultad Respiratoria del Adulto. Finalmente cae en asistolia, y la paciente fallece. En este caso, el Síndrome HELLP se presenta con sintomatología de pocas horas de evolución lo cual no es común encontrar. Destacamos el hecho que la hipertensión no fue un evento significativo. En la literatura investigada no encontramos casos similares reportados en el país.

The expression of cyclooxygenase-2 in human umbilical vein endothelial cell culture from preeclampsia.

We have shown the HUVEC from normal pregnancy contained COX-1 protein but not COX-2 protein and released 6-keto-PGF1 alpha 277 +/- 5 ng/ml (for 24 h). In contrast, HUVEC from preeclampsia contained both COX-1 and COX-2 protein and released significantly lesser amounts of 6-keto-PGF1 alpha (159 +/- 8 ng/ml for 24 h; p < 0.05). Thus, COX-2 is expressed in HUVEC from preeclampsia but not in normal pregnancy and affects the release of prostacyclin suggesting the involvement of COX-2 in the pathogenesis of preeclampsia. The development of selective inhibitors of COX-2 may have a potential role in prevention and treatment of preeclampsia.

Actividad de las enzimas reguladoras del metabolismo de los carbohidratos en la placenta preeclámptica / Pre-eclampsia placental carbohydrate metabolism regulating enzymes activity

La preeclampsia es una de las patologías más frecuente en el embarazo. La placenta juega un papel importanteen el desarrollo del cuadro. En el presente trabajo realizamos un estudio de las actividades de dos enzimas reguladoras [fosfofructoquinasa I (C.E.2.7.1.11) y glucosa 6-P deshidrogenasa (C.E.1.1.149)] en el metabolismo de los carbohidratos en el tejido placentario normal y en el preeclámptico a término. Se halla una marcada disminución de las actividades de ambas enzinas en los tejidos patológicos. Se discute los posibles mecanismos.