PD-1/PD-L1 regulates Treg differentiation in pregnancy-induced hypertension

Pregnancy-induced hypertension (PIH) causes significant maternal and fetal morbidity and mortality. A decreased number of regulatory T (Treg) cells is associated with the pathogenesis of PIH. The programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway is critical to normal pregnancy (NP) by promoting Treg cell development. However, the relationship between PD-1/PD-L1 and Treg differentiation in PIH has not been fully elucidated. In this study, venous blood was obtained from 20 NP and 58 PIH patients. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. The levels of Treg-related cytokines (TGF-β, IL-10, and IL-35) in serum and PBMCs were measured by ELISA. The percentage of Treg cells in PBMCs was assessed by flow cytometry. The mRNA levels of Treg-specific transcription factor Foxp3 in PBMCs, and PD-1 and PD-L1 in Treg cells were detected by qRT-PCR. The protein levels of PD-1 and PD-L1 in Treg cells were evaluated by western blot. The serum levels of TGF-β, IL-10, IL-35, and Foxp3 mRNA expression and CD4+CD25+ Treg cell percentage in PBMCs were decreased in PIH. Furthermore, a significant increase of PD-1 in Treg cells was found in PIH compared with NP. In addition, PD-L1 Fc, an activator of PD-1/PD-L1 pathway, increased Treg cell percentage, enhanced Foxp3 mRNA expression, and elevated levels of TGF-β, IL-10, and IL-35 in PBMCs. However, anti-PD-L1 mAb exerted a reverse effect. These findings revealed that PD-L1 Fc had a favorable effect on Treg cell differentiation, indicating a potential therapeutic value of PD-1/PD-L1 pathway for PIH treatment.

Inflammatory and oxidative stress airway markers in premature newborns of hypertensive mothers

Although oxidative stress and inflammation are important mechanisms in the pathophysiology of preeclampsia and preterm diseases, their contribution to the respiratory prognosis of premature infants of hypertensive mothers is not known. Our objective was to determine the levels of oxidative stress and inflammation markers in the airways of premature infants born to hypertensive and normotensive mothers, in the first 72 h of life, and to investigate whether they are predictors of bronchopulmonary dysplasia (BPD)/death. This was a prospective study with premature infants less than 34 weeks’ gestation on respiratory support who were stratified into 2 groups: 32 premature infants of hypertensive mothers and 41 of normotensive women, with a mean gestational age of 29 weeks. Exclusion criteria were as follows: diabetes mellitus, chorioamnionitis, malformation, congenital infection, and death within 24 h after birth. The outcome of interest was BPD/death. Malondialdehyde (MDA), nitric oxide (NO), and interleukin 8 (IL-8) were measured in airway aspirates from the first and third days of life and did not differ between the groups. Univariate and multivariate statistical analyses were performed. The concentrations of MDA, NO, and IL-8 were not predictors of BPD/death. Premature infants who developed BPD/death had higher levels of IL-8 in the first days of life. The gestational age, mechanical ventilation, and a small size for gestational age were risk factors for BPD/death. In conclusion, the biomarkers evaluated were not increased in premature infants of hypertensive mothers and were not predictors of BPD/death.

Análise da composição corporal materna pela impedância bioelétrica e sua aplicação na Obstetrícia / Maternal body composition analysis by bioelectrical impedance and its Obstetrical appliance

A análise da impedância bioelétrica é o método de avaliação da composição corporal, que é rápido e fácil de ser aplicado, permitindo a determinação da massa livre de gordura, da massa celular corporal e da água corporal total, extra e intracelular. Várias técnicas são descritas na literatura, com diferentes métodos de análise da impedância. É frequentemente utilizada na prática clínica em diversas situações como: adultos e idosos saudáveis. Porém, a análise deve ser ajustada de acordo com a raça, etnia, idade, sexo e alterações de massa livre de gordura e gordura corporal. Existem poucos estudos sobre sua aplicabilidade em mulheres grávidas, apesar de ser método de fácil aplicação para avaliar a composição corporal, além de não expor a gestante a radiações. Particularidades da gestação, tais como a hemodiluição, a alteração da geometria corporal e o acúmulo de líquido na cavidade amniótica são aspectos que podem influenciar os resultados da análise. Sua aplicabilidade na obesidade e na desnutrição demanda, algumas vezes, equações ajustadas para a população alvo. A origem da análise da impedância bioelétrica é fundamentada pelas propriedades elétricas dos tecidos que são relacionados ao seu conteúdo de água e eletrólitos. Apesar de a impedância bioelétrica ser método promissor na avaliação da composição corporal materna, é necessário que estudos obtenham informações mais precisas e validadas.(AU)

The bioelectrical impedance analysis is a method to evaluate body composition, easy and fast applied, allowing the determination of the fat-free mass, body cell mass and total body water, extra and intracellular. A lot of techniques are described in the literature, with different methods of impedance analysis. It is frequently used at clinical practice in healthy elderly and adults. However, the analysis may be adjusted with race, ethnic group, age, sex, fat free mass and body fat. There are few studies about applicability in pregnancies, despite of being an easy method to evaluate body composition and do not expose the pregnant woman to radiation. Pregnancy particularities as maternal hemodilution, body geometry change, and the fluid accumulation in amniotic cavity are aspects that may influence the results. Its applicability in obesity and malnutrition demand, sometimes, equations adjusted for target population. The origin of the bioelectrical impedance analysis is supported by electrical properties of the tissues that are related to their water and electrolytes content. The bioelectrical impedance is a promissory method to evaluate maternal body composition. However, more studies are needed to establish its accuracy and validity.(AU)

Endogenous ouabain in hypertensive disorder complicating pregnancy / 华中科技大学学报（医学）（英德文版）

Expression of endogenous ouabain in placenta and the concentrations of serum ET-1 and NO were examined in 30 patients with hypertensive disorder complicating pregnancy (HDCP) and 30 healthy pregnant women to investigate the effect of endogenous ouabain on HDCP. Compared with the healthy pregnant group, the expression of endogenous ouabain dramatically increased in the HDCP groups (P<0.01). There was a significantly positive correlation between the expression of endogenous ouabain with ET-1 (r=0.5567, P<0.01), while the correlation of endogenous ouabain and NO was significantly negative (r=-0.6895, P<0.01). As expected, the correlation between ET-1 and NO was negative (r=-0.7796, P<0.01). ET-1 concentrations of maternal and cord sera in HDCP groups were significantly higher in comparison with healthy pregnant group (P<0.01). On the contrast, NO concentrations were much lower in the maternal and cord sera of HDCP groups as compared with healthy pregnant group (P<0.01). Our data suggest that endogenous ouabain is directly involved in the nosogenesis of HDCP, with accompanying decreased NO and the elevated of ET-1.

Avaliação epidemiológica da ocorrência de insuficiência renal aguda na síndrome HELLP em um Hospital Geral no Oeste do Paraná / Epidemiological evaluation of acute renal failure occurrence in HELLP syndrome in General Hospital in West Paraná

Introdução: A síndrome HELLP é a mais frequente causa de insuficiência renal aguda gestacional e apresenta uma alta morbimortalidade maternal eperinatal. Métodos: Pacientes com síndrome HELLP foram identificadas em um estudo retrospectivo entre julho de 2002 e julho de 2005 no HospitalUniversitário do Oeste do Paraná. Resultados: Síndrome HELLP ocorreu em 12 casos (0,2%) de um total de 6000 partos. Insuficiência renal aguda foi diagnosticada em oito pacientes (66,7%), sendo que uma necessitou de diálise e evoluiu para óbito. Quanto aos recém-nascidos, o peso médio foi 1500+ 113 g, variando de 200 a 2940 g. Membrana hialina ocorreu em 25% dos casos; a taxa de mortalidade foi de 33,4%. Conclusões: Insuficiência renalaguda é freqüente na síndrome HELLP e contribui para a morbimortalidade materno-fetal.

Introduction: HELLP syndrome (HS) is the most frequent cause of obstetric acute renal failure and has a high maternal and perinatal morbidity and mortality rate. Methods: Patients with HELLP syndrome were identified in a retrospective study between July 2002 and July 2005 at the Hospital Universitário do Oeste do Paraná. Results: HS was diagnosed in twelve (0.2%) patients of 6000 deliveries. Acute renal failure (ARF) was found in eight (66.7%) patients with HS. Dialysis was required in one patient who had an unfavorable course. The mean body weight of the newborns was 1.500 + 113 g (200 to 2.940 g).The frequency of hyaline membrane disease was 25%; the mortalility rate was 33.4%. Conclusions: Acute renal failure is frequent in HS and can beassociated with higher maternal and perinatal morbidity and mortality.

Expression of TGF-betal in placenta of the patients with pregnancy-induced hypertension and its relationship with serum VCAM-1 / 华中科技大学学报（医学）（英德文版）

The expression of transforming growth factor-beta1 (TGF-beta1) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of TGF-beta1 and the amount of vascular cell adhesion molecule-1 (VCAM-1) in serum was studied. Immunohistochemistry ABC was used to detect the expression and distribution of TGF-beta1 in placental tissues in 40 PIH women and 20 normal pregnancy women. High resolution pathological image analysis system was used to determine the quality of TGF-beta1. The VCAM-1 in serum was examined by enzyme linked immunoabsorbent assay (ELISA). The results showed that TGF-beta1 could be express in syncytiotrophoblast. The levels of TGF-beta1 expression in placental tissues of the patients with moderate and severe PIH were significantly higher (P < 0.05), while the serum VCAM-1 was significantly lower than in normal group (P < 0.01). There was a significant positive correlation between the expression of TGF-beta1 in placental tissues and the serum VCAM-1 (r = 0.969, P < 0.01). It was concluded that the level of TGF-beta1 expression in PIH was increased and was positively correlated with the amount of serum VCAM-1, indicating that they might be involved in the pathogenesis of PIH.