Serum uric acid levels associated with biochemical parameters linked to preeclampsia severity and to adverse perinatal outcomes.

AIMS: Evaluating the association between serum uric acid levels and biochemical parameters linked to preeclampsia (PE) severity and to adverse perinatal outcomes. METHODS: Cross-sectional study. Information about gestational and biochemical parameters were collected before delivery, whereas perinatal outcomes were observed after it. Pregnant women were divided into hyperuricemia-HU (uric acid ≥ 6 mg/dL) or normouricemia (uric acid, 2.6-5.9 mg/dL) groups. Poisson regression models (prevalence ratio-PR; 95% confidence interval-95% CI), multinomial logistic regression (odds ratio-OR; 95% CI), and Pearson's correlation (correlation coefficient-r) were applied by taking into consideration p < 0.05 as significance level. RESULTS: The total sample comprised 267 pregnant women with PE. HU was observed in 25.8% of patients; it was associated with black pregnant women (p = 0.014) and with primiparity (p = 0.007). Uric acid levels were higher in early PE cases than in late PE cases (p = 0.013); however, there was no significant difference between mild and severe PE cases (p = 0.121). Uric acid recorded a positive correlation to urea (p < 0.001), creatinine (p = 0.002), glutamic-oxaloacetic transaminase (p < 0.001), glutamic-pyruvic transaminase (p = 0.005), ferritin (p = 0.002) and globulin (p = 0.002); as well as negative correlation to platelets (p = 0.035), lactic dehydrogenase (p = 0.039) and albumin (p > 0.001). HU was a factor associated with cesarean delivery (p = 0.030), prematurity (p = 0.001), low birth weight (p < 0.001) and small for gestational age (p = 0.020). CONCLUSION: High serum uric acid levels were associated with early-onset PE. Maternal features were correlated to biochemical parameters linked to PE severity and to adverse perinatal outcomes.

Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies.

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes.

OBJECTIVE: To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. METHODS: A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level (α = 0.05), with the chi-square test, the Wilcoxon-Mann-Whitney test, and the multinomial and Poisson regression tests. RESULTS: One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) (p ≤ 0.001), glutathione peroxidase (GPx) (p = 0.016), and malondialdehyde (MDA) (p = 0.028) and lower levels of IL-6 (p = 0.030) and TNF-α (p ≤ 0.001) than the other group, with some associations among these biomarkers with perinatal outcomes. CONCLUSION: The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.

Validation and reproducibility of a FFQ focused on pregnant women living in Northeastern Brazil.

OBJECTIVE: The aim of the current study is to assess the validity and reproducibility of a FFQ focused on pregnant women living in Northeastern Brazil. DESIGN: Three 24-hour-dietary recalls (24 hR) and two FFQ were applied at 15-d intervals between research stages in order to confirm the validity and reproducibility of the FFQ. Validity assessment was based on Pearson's correlation coefficient (PCC) or Spearman's correlation coefficient (SCC) between FFQ and the mean of three 24 hR (the 24 hR was used as reference standard), whereas reproducibility assessment was based on the intraclass correlation coefficient (ICC) among FFQ, and P < 0·05 was set as significance level. SETTING: Public health network of a capital city in Northeastern Brazil. PARTICIPANTS: Overall, 100 pregnant women were included in the study. RESULTS: The PCC or SCC adopted in the validity analysis recorded the recommended values (from 0·4 and 0·7) for energy (0·44; P < 0·001), carbohydrate (0·40; P < 0·001), vitamins B2 (0·40; P < 0·001), B5 (0·40; P < 0·001), E (0·47; P < 0·001), B12 (0·48; P < 0·001), phosphorus (0·92; P < 0·001), Mg (0·81; P < 0·001), Se (0·70; P < 0·001), cholesterol (0·64; P < 0·001), saturated (0·76; P < 0·001), polyunsaturated (0·73; P < 0·001) and monounsaturated fats (0·87; P < 0·001) and fibres (0·77; P < 0·001). Mg (0·72; P < 0·001), Fe (0·65; P < 0·001), lipid (0·56; P < 0·001) and energy (0·55; P < 0·001) presented ICC within the recommended reproducibility values. CONCLUSIONS: The FFQ developed in the current study is a useful tool to assess the usual food intake of pregnant women.

Premature birth, low birth weight, small for gestational age and chronic non-communicable diseases in adult life: A systematic review with meta-analysis.

BACKGROUND: Individuals who were born prematurely (PT), with low birth weight (LBW), or small for gestational age (SGA) appear to present a set of permanent changes that make them more susceptible to develop chronic non-communicable diseases (CNCD) in adult life. AIM: Investigating the association between PT birth, LBW or SGA at birth and CNCD incidence in adult life. METHODS: Systematic review with meta-analysis of studies available in three databases - two of them are official (PubMed and Web of Science) and one is gray literature (OpenGrey) - based on pre-established search and eligibility criteria. RESULTS: Sixty-four studies were included in the review, 93.7% of them only investigated one of the exposure variables (46.7% LBW, 35.0% PT and 18.3% SGA at birth), whereas 6.3% investigated more than one exposure variable (50.0% LBW and PT; 50.0% SGA and PT). There was association among all exposure variables in the following outcomes: cardiometabolic (CMD) and glycidic metabolism (GMD) disorders, changes in body composition and risk of developing metabolic syndrome (MS). Female sex was identified as risk factor in the exposure-outcome association. Eighteen (18) articles were included in the meta-analysis. There was positive association between LBW and incidence of CMD (OR: 1.25 [95%CI: 1.11; 1.41]; 07 studies), GMD (OR: 1.70 [95%CI: 1.25; 2.30]; 03 studies) and MS (OR: 1.75 [95%CI: 1.27; 2.40]; 02 studies) in adult life. PT was positively associated with CMD (OR: 1.38 [95%CI: 1.27; 1.51]; 05 studies). CONCLUSIONS: LBW and PT are associated with CMD and GMD development, as well as with the risk of developing MS in adult life.

Oxidative stress markers in preeclamptic placentas: A systematic review with meta-analysis.

INTRODUCTION: Oxidative stress (OS) is the basis of several diseases. Preeclampsia (PE) is a multisystemic syndrome, considered one of the major causes of maternal and fetal mortality. The placenta is considered the main anatomical pathogenetic substrate for the disease, being the placental OS a likely critical pathway in the pathogenesis of PE. This meta-analysis aimed to verify whether there is OS in the preeclamptic placenta and which markers are altered in this condition. METHODS: The search was conducted in the following databases: MEDLINE (via PubMed), Lilacs and Scopus. Relevant studies were identified until May 2020. The quality of the studies was evaluated according to the Newcastle-Ottawa scale. RESULTS: From the 3998 screened records, 43 were finally included in the systematic review, and 23 in the meta-analysis. The biomarkers evaluated were related to cell and macromolecules' damage, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), lipid peroxides, isoprostane, total oxidant status (TOS), carbonylated proteins and some of the reactive oxygen and nitrogen species (RONS), like hydrogen peroxide and nitric oxide. It was also related to antioxidant activity, both enzymatic, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase and total antioxidant status, and non-enzymatic, through quantification of reduced glutathione, vitamin C and E, zinc and copper. CONCLUSION: It was observed that there was OS in the preeclamptic placentas, based on results, like lower activity of some of the enzymes of the antioxidant system (SOD and GPx) as well as the increase in oxidative damage markers (MDA and lipid peroxide), corroborating literature data.

Pre-eclampsia is associated with later kidney chronic disease and end-stage renal disease: Systematic review and meta-analysis of observational studies.

OBJECTIVES: To assess whether there is a risk of kidney disease during the postpartum period of women who had preeclampsia (PE). STUDY DESIGN: Observational trials were searched in the PubMed, Science Direct, Clinical trials, Cochrane, LILACS and Web of Science databases. The data extracted from the studies were systematized, and the risk of bias was evaluated for each of them. Meta-analyses were performed with studies that evaluated chronic kidney disease (CKD) and end-stage renal disease (ESRD), pooling the natural logarithms of the adjusted risk measures and the confidence intervals of each study in a random effects model. RESULTS: Of the 4149 studies evaluated, 35 articles were included in the review, of which 3 of the CKD and 6 of the ESRD presented the necessary outcomes to compose the meta-analysis. A formal registration protocol was included in the PROSPERO database (number: CRD42019111821). There was a statistically significant difference between the development of CKD (hazard ratio (HR): 1.82, confidence interval to 95% (95% CI): 1.27-2.62, P < 0.01) and ESRD (HR: 3.01, confidence interval to 95% (95% CI): 1.92-4.70, P < 0.01) in postpartum women affected by PE. CONCLUSIONS: PE was considered a risk factor for the onset of CKD and ESRD in the postpartum period. Thus, more research is needed to clarify the underlying mechanisms of this association, and to assist in determining the most appropriate and effective clinical conduct to prevent and/or treat such complications.

Cross-Talk between Oxidative Stress and Inflammation in Preeclampsia.

The occurrence of hypertensive syndromes during pregnancy leads to high rates of maternal-fetal morbidity and mortality. Amongst them, preeclampsia (PE) is one of the most common. This review aims to describe the relationship between oxidative stress and inflammation in PE, aiming to reinforce its importance in the context of the disease and to discuss perspectives on clinical and nutritional treatment, in this line of research. Despite the still incomplete understanding of the pathophysiology of PE, it is well accepted that there are placental changes in pregnancy, associated with an imbalance between the production of reactive oxygen species and the antioxidant defence system, characterizing the placental oxidative stress that leads to an increase in the production of proinflammatory cytokines. Hence, a generalized inflammatory process occurs, besides the presence of progressive vascular endothelial damage, leading to the dysfunction of the placenta. There is no consensus in the literature on the best strategies for prevention and treatment of the disease, especially for the control of oxidative stress and inflammation. In view of the above, it is evident the important connection between oxidative stress and inflammatory process in the pathogenesis of PE, being that this disease is capable of causing serious implications on both maternal and fetal health. Reports on the use of anti-inflammatory and antioxidant compounds are analysed and still considered controversial. As such, the field is open for new basic and clinical research, aiming the development of innovative therapeutic approaches to prevent and to treat PE.

Intake of antioxidant nutrients and coefficients of variation in pregnant women with preeclampsia. / Ingestão e coeficiente de variabilidade de nutrientes antioxidantes por gestantes com pré-eclâmpsia.

INTRODUCTION AND OBJECTIVE: Oxidative stress appears to play a critical role in the pathogenesis of preeclampsia. Evidence suggests that adequate intake of antioxidants can modulate this condition. The objective of this study was to assess the intake of antioxidant nutrients and coefficients of variation in pregnant women with preeclampsia. METHODS: In a cross-sectional study in the public health network of the city of Maceió, Brazil, a dietary survey was performed consisting of 24-hour food recalls, with subsequent adjustment of nutrients using the estimated average requirement as the cutoff point, and a questionnaire on frequency of consumption of antioxidants. RESULTS: We studied 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP) with mean ages of 25.8±6.7 years and 24.1±6.2 years (p=0.519), respectively. A low mean intake of antioxidants (vitamin A, selenium, zinc and copper) was observed in both PWP and PWoP, although intakes of vitamin A (p=0.045) and selenium (p=0.008) were higher in PWoP. In addition, we observed high coefficients of variation in nutrient intakes in both groups, which were higher for vitamin C (p<0.001), vitamin A (p=0.006) and copper (p=0.005) in PWP. CONCLUSIONS: Consumption of antioxidant nutrients by pregnant women with preeclampsia is inadequate, with considerable daily variations in intake, which points to a need for nutrition education strategies aimed at improving intakes, because diet is without doubt a key factor in the modulation of oxidative stress caused by preeclampsia.

Maternal Factors and Adverse Perinatal Outcomes in Women with Preeclampsia in Maceió, Alagoas.

BACKGROUND: Preeclampsia has been associated with several risk factors and events. However, it still deserves further investigation, considering the multitude of related factors that affect different populations. OBJECTIVE: To evaluate the maternal factors and adverse perinatal outcomes in a cohort of pregnant women with preeclampsia receiving care in the public health network of the city of Maceió. METHODS: Prospective cohort study carried out in 2014 in the public health network of the city with a sample of pregnant women calculated based on a prevalence of preeclampsia of 17%, confidence level of 90%, power of 80%, and ratio of 1:1. We applied a questionnaire to collect socioeconomic, personal, and anthropometric data, and retrieved perinatal variables from medical records and certificates of live birth. The analysis was performed with Poisson regression and chi-square test considering p values < 0.05 as significant. RESULTS: We evaluated 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP). A previous history of preeclampsia (prevalence ratio [PR] = 1.57, 95% confidence interval [95% CI] 1.47 - 1.67, p = 0.000) and black skin color (PR = 1.15, 95% CI 1.00 - 1.33, p = 0.040) were associated with the occurrence of preeclampsia. Among the newborns of PWP and PWoP, respectively, 12.5% and 13.1% (p = 0.907) were small for gestational age and 25.0% and 23.2% (p = 0.994) were large for gestational age. There was a predominance of cesarean delivery. CONCLUSION: Personal history of preeclampsia and black skin color were associated with the occurrence of preeclampsia. There was a high frequency of birth weight deviations and cesarean deliveries.

[Risk factors associated among anemia in pregnancy women of network public health of a capital of Brazil Northeastern]. / Fatores de associados à anemia em gestantes da rede pública de saúde de uma capital do Nordeste do Brasil.

PURPOSE: To evaluate the factors associated with anemia among pregnant women receiving public health care in a capital city in Northeastern Brazil. METHODS: This was a cross-sectional study conducted on a sample of 428 patients obtained on the basis of the estimated prevalence of anemia during pregnancy (50%), a 95% confidence interval (95%CI), an error of 5% and a sample loss of 20%. Pregnant women who lived in the city and were served by the municipal public health network were considered to be eligible for the study. Socioeconomic, lifestyle, clinical and anthropometric data and dietary iron intake were obtained, and capillary hemoglobin was determined. Anemia was identified as a hemoglobin level <11 g/dL, and its association with risk factors was tested using multivariate Poisson regression analysis, with the results expressed as the Prevalence Ratio (PR) and 95%CI. RESULTS: The prevalence of anemia was 28.3% and was higher among women with more members in the household (PR=1.49; 95%CI 1.01-2.22; p=0.046) and those living with food insecurity (PR=1.43; 95%CI 1.00-2.04; p=0.047). CONCLUSION: The prevalence of anemia among pregnant women receiving care from the public health system of the city is a moderate public health problem, requiring the planning of effective measures for its control.

Molecular mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene on HL-60 leukemia cells.

The aim of this work was to investigate the mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene (1) on HL-60 human leukemia cells. While inactive against noncancerous cells, 1 provoked a concentration-dependent decrease in viable tumor cells, primarily via apoptosis, as evidenced by analysis of cell morphology, activation of caspases 3 and 7, increased DNA fragmentation, and externalization of phosphatidylserine. Necrosis was observed only at the highest tested concentration (4 µM). Compound 1 interfered with the cell cycle, causing an accumulation of cells in the G1 /G0 phase. Interaction of 1 with dsDNA and ssDNA was observed by differential pulse voltammetry and confirmed by hyperchromicity in the UV/Vis spectra of dsDNA, with an interaction constant of 2×10(4) M(-1). Both the organic analogue 1,1,2-triphenylbut-1-ene (2) and ferrocene were inactive against cancer and noncancer cell lines and did not react with DNA. These results reinforce the idea that the hybrid strategy of conjugating ferrocene to the structure of tamoxifen derivatives is advantageous in finding new substances with antineoplastic activity.

Biological evaluation of twenty-eight ferrocenyl tetrasubstituted olefins: cancer cell growth inhibition, ROS production and hemolytic activity.

The antiproliferative effects of twenty-eight tetrasubstituted olefins bearing a ferrocenyl group, including six never-reported compounds, were evaluated against SF-295 (human glioblastoma), HCT-8 (human colon cancer), MDA-MB-435 (human melanoma) and HL-60 (human promyelocytic leukemia) using the MTT test. IC(50) values were determined for twenty-three active compounds and of these, ten compounds had IC(50) values lower than 2 µM on one or more cell lines. Of all the compounds, only two produced significant amounts of ROS on HL-60 cells, and ROS production and growth inhibition could not be correlated. The ten most antiproliferative compounds were tested for their hemolytic activity on mouse erythrocytes. Five compounds showing high antiproliferative activity and low hemolytic activity were thus identified for further study.