Down-regulation of autophagy proteins is associated with higher mTOR expression in the placenta of pregnant women with preeclampsia

Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged organelles maintaining cellular integrity. It seems to be essential for cell survival during stress, starvation, hypoxia, and consequently to the placenta implantation and development. Preeclampsia (PE) is a multisystemic disorder characterized by the onset of hypertension associated or not with proteinuria and other maternal complications. Considering that the placenta seems to play an important role in the pathogenesis of PE, the objective of the present study was to evaluate protein levels of light chain protein (LC3), beclin-1, and the mammalian target of rapamycin (mTOR) in the placenta of pregnant women with PE. Placental tissues collected from 20 women with PE and 20 normotensive (NT) pregnant women were evaluated for LC3, beclin-1, and mTOR expression by qPCR and immunohistochemistry. The mRNA for LC3 and beclin-1 were significantly lower, while mTOR gene expression was significantly higher in the placenta of pregnant women with PE than in the NT group. Placentas of PE women showed significantly decreased protein expression of LC3-II and beclin-1, whereas mTOR was significantly increased compared with the NT pregnant women. There was a negative correlation between protein expression of mTOR and LC3-II in the placental tissue of PE women. In conclusion, the results showed autophagy deficiency suggesting that failure in this degradation process may contribute to the pathogenesis of PE; however, new studies involving cross-talk between autophagy and inflammatory molecular mechanisms might help to better understand the autophagy process in this obstetric pathology.

Effects of vitamin D-induced supernatant of placental explants from preeclamptic women on oxidative stress and nitric oxide bioavailability in human umbilical vein endothelial cells

The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.

Effect of maternal hydration on the increase of amniotic fluid index

The objective of this study was to determine the effect of maternal hydration with oral isotonic solution and water on the amniotic fluid (AF) index of women with normohydramnios. Women with a normal AF index and gestational age between 33 and 36 weeks without maternal complications were randomized into three groups [isotonic solution (Gatorade®), water, control]. The isotonic solution and water groups were instructed to drink 1.5 L of the respective solution and the control group was instructed to drink 200 mL water over a period of 2 to 4 h. AF index was measured before and after hydration by Doppler ultrasonography. The investigator performing the AF index measurement was blind to the subject’s group. Ninety-nine women completed the study without any adverse maternal effects. The median increase in AF index after hydration was significantly greater for the isotonic solution and water groups than for the control group. There was no significant difference between the isotonic solution and water groups. Hydration with isotonic solution and water caused a 10-fold (95 percentCI: 2.09-49.89) and 6-fold (95 percentCI: 1.16-30.95) increase in the chance of a 20 percent increase of AF index, respectively. Maternal hydration with isotonic solution or water increased the AF index in women with normohydramnios.

Studies of natural killer cells in pregnancy-induced hypertension

The number and activity of natural killer (NK) cells were studied in 20 patients with pregnancy-induced hypertension (PIH), 15 uncomplicated pregnant women and 16 healthy non-pregnant women. All the pregnant women were evaluated during the third trimester of gestation. Peripheral blood NK cells were detected with monoclonal antibodies by indirect immunofluorescence and cytotoxic activity was measured using a single-cell assau against K562 target cells, Hypertensive pregnant women had an increased number of circulating NK cells associated with a significant decrease of NK activity. The cytotoxic activity was significantly lower in normal pregnant and PIH women when compared with non-pregnant controls. The onset of immune NK cells in peripheral blood and the impairment of their cytotoxic activity in PIH patients may be associated with hormones and immunosuppresive substances produced by tissues occurring at the maternal-fetal interface

The oral glucose tolerance test is a poor predictor of hyperglycemia during pregnancy

1. In the order to assess the efficacy of the use of the diurnal plasma glucose profile rather than that of the glucose tolerance tes (GTT) to predict hyperglycemia during pregnancy, we compared the results of the two tests. A total of 192 pregnant women seen at the Prenatal Clinic of the Faculty of Medicine of Botucatu were submitted to the glucose tolerance test (GTT) and determination of diurnal plasma glucose profile. 2. On the basis of two blood tests (GTT) and diurnal plasma glucose profile). the subjects were divided into four groups: Group I-A, normal GTT and profile (79 patients, 41.2%); Group I-B, normal GTT and altered profile (63 patients, 32.8%); Group II-A, altered GTT and normal profile (18 patients, 9.4%) Group II-B, altered Gtt and profile (32 patients, 16,7%). 3. Large babies were delivered by 25.6% of Group I-A, 53.8% of GroupI-B28.6% of Group II-A and 51.9% of Group II-B patients. Group I-A patients are normoglycemic, Group I-B patients have intolerance to carbohydrates, protein and lipides, Group II-A patients have intolerance to high carbohydrate amounts, especially in the form of glucose, and Group II-B patients are diabetic. 4. We propose that Group I-A patients should receive no treatment, Group II-A patients should be adivised to avoid excess carbohydrate intake and Groups I-B and II-B patients should be places on a low-calorie diet and treated with insulin if necessary to obtain normal blood glucose levels. 5. Routine determination of blod glucose levels under fasting conditions represents a screening method for diabetes and values of > ou = 90 mg/dl identify a population at risk that should be submitted to GTT and determination of plasma glucose profile