Eucommia granules activate Wnt/ß-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats.

PURPOSE: Pre-eclampsia (PE) is a pregnancy-related complication. Eucommia is effective in the treatment of hypertensive disorders in pregnancy, but the specific effects and possible mechanisms of Eucommia granules (EG) in PE remain unknown. The aim of this study was to investigate the effects and possible mechanisms of EG in PE rats. METHODS: Pregnant Sprague Dawley rats were divided into five groups (n = 6): the control group, the model group, the low-dose group, the medium-dose group, and the high-dose group of EG. The PE model was established by subcutaneous injection of levonitroarginine methyl ester. Saline was given to the blank and model groups, and the Eucommia granules were given by gavage to the remaining groups. Blood pressure and urinary protein were detected. The body length and weight of the pups and the weight of the placenta were recorded. Superoxide dismutase (SOD) activity and levels of malondialdehyde (MDA), placental growth factor (PIGF), and soluble vascular endothelial growth factor receptor-1 (sFIt-1) were measured in the placenta. Pathological changes were observed by hematoxylin-eosin staining. Wnt/ß-catenin pathway-related protein expression was detected using Western blot. RESULTS: Compared with the model group, the PE rats treated with EG had lower blood pressure and urinary protein. The length and weight of the pups and placental weight were increased. Inflammation and necrosis in the placental tissue was improved. SOD level increased, MDA content and sFIt-1/PIGF ratio decreased, and Wnt/ß-catenin pathway-related protein expression level increased. Moreover, the results of EG on PE rats increased with higher doses of EG. CONCLUSIONS: EG may activate the Wnt/ß-catenin pathway and inhibit oxidative stress, inflammation, and vascular endothelial injury in PE rats, thereby improving the perinatal prognosis of preeclamptic rats. EG may inhibit oxidative stress, inflammation, and vascular endothelial injury through activation of the Wnt/ß-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

Improved neonatal outcomes in pregnancies with coexisting gestational diabetes and preeclampsia in normal birthweight neonates- insights from a retrospective cohort study.

INTRODUCTION: We aimed to assess neonatal and maternal outcomes in appropriate-for-gestational-weight (AGA) neonates of mothers with both gestational diabetes mellitus (GDM) and preeclampsia (PET). METHODS: Medical records of women diagnosed with GDM or PET were reviewed. Women with AGA neonates were divided into three groups- GDM, PET, and GDM + PET and maternal neonatal and placental outcomes were compared. The primary outcome was a composite of adverse neonatal outcomes, including intensive care unit admission (NICU), neurological morbidity, hypoglycemia, ventilation, respiratory distress syndrome (RDS), phototherapy, sepsis, blood transfusion, and neonatal death. Post-hoc analysis was performed to determine between-group significance. RESULTS: Composite adverse neonatal outcomes are significantly lower in women with multiple morbidities compared to women with confined PET (p = 0.015), and a similar trend is observed when comparing neonatal outcomes between women with GDM to those with GDM + PET, yet these results are underpowered (18.9 % vs. 12.8 % respectively, p = 0.243). Placentas of women with GDM + PET were larger, with a lower rate of placentas below the 10th percentile as compared to placentas of women with isolated PET (p < 0.001), but with similar rates of MVM lesions. DISCUSSION: While maternal and placental outcomes in patients of the GDM + PET group resemble the characteristics of the PET group, surprisingly, the neonatal outcomes in this group are significantly better compared to isolated morbidities. The paradoxical benefit attributed to the coexistence of GDM + PET may be explained by a balance of the opposing trends characterizing these morbidities-the reduced blood and nutrient supply characterizing PET vs. chronic overflow and abundance typical of GDM. CLINICAL TRIAL REGISTRATION: approval of local ethics committee WOMC-19-0152.

Cyclosporin A alleviates trophoblast apoptosis and senescence by promoting autophagy in preeclampsia.

INTRODUCTION: Abnormal extravillous trophoblast (EVT) function is closely related to preeclampsia (PE) and may be caused by inadequate autophagy, apoptosis, and senescence. Cyclosporin A (CsA) is an effective immunosuppressant that has been reported to stimulate autophagy and exert benign biological effects on EVTs. Therefore, we hypothesized that CsA may display therapeutic efficacy against PE by activating autophagy. METHODS: We established the nitro-l-arginine methyl ester (l-NAME)-induced preeclamptic mice model and a hypoxia-reoxygenation (H/R) model in vitro. The effects of CsA on autophagy were evaluated by western blotting (WB). The effects of CsA on apoptosis were analyzed by Hematoxylin-eosin (H&E) staining, cell apoptosis assay and WB. Senescence-associated ß-galactosidase (SA-ß-gal) staining, RT-qPCR and WB were used to examine the senescence level. RT-qPCR were used to detect the senescence-associated secretory phenotype (SASP) level. DCFH-DA fluorescent probe, dihydroethidium (DHE) staining and mitochondrial membrane potential (ΔΨm) were used to detect senescence-associated mitochondrial dysfunction (SAMD). RESULTS: CsA alleviated PE-like symptoms and reduced placental necrosis and senescence in mice injected with l-NAME. CsA ameliorated placental SASP and SAMD level induced by l-NAME. CsA also upregulated the expression of autophagic proteins in mouse placentas disrupted using l-NAME. In vitro, we found that CsA reversed H/R-induced apoptosis and senescence, as well as decreasing SASP and SAMD levels and upregulating autophagic proteins levels. Notably, 3-methyladenine (3-MA), an early phase inhibitor of autophagosome formation, abolished the protective effects of CsA against H/R. DISCUSSION: CsA may display some therapeutic effects against PE by activating autophagy in vivo and in vitro.

The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction.

Ghrelin and nesfatin-1 are enteroendocrine peptide hormones expressed in rat X/A-like and human P/D1cells of the gastric mucosa. Besides their effect on food intake, both peptides are also implicated in various other physiological systems. One of these is the reproductive system. This present review illustrates the distribution of ghrelin and nesfatin-1 along the hypothalamus-pituitary-gonadal (HPG) axis, their modulation by reproductive hormones, and effects on reproductive functions as well as highlighting gaps in current knowledge to foster further research.

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders.

Pregnancy is a challenging physiological process that involves maternal adaptations to the increasing energetics demands imposed by the growing conceptus. Failure to adapt to these requirements may result in serious health complications for the mother and the baby. The mitochondria are biosynthetic and energy-producing organelles supporting the augmented energetic demands of pregnancy. Evidence suggests that placental mitochondria display a dynamic phenotype through gestation. At early stages of pregnancy placental mitochondria are mainly responsible for the generation of metabolic intermediates and reactive oxygen species (ROS), while at later stages of gestation, the placental mitochondria exhibit high rates of oxygen consumption. This review describes the metabolic fingerprint of the placental mitochondria at different stages of pregnancy and summarises key signs of mitochondrial dysfunction in pathological pregnancy conditions, including preeclampsia, gestational diabetes and intrauterine growth restriction (IUGR). So far, the effects of placental-driven metabolic changes governing the metabolic adaptations occurring in different maternal tissues in both, healthy and pathological pregnancies, remain to be uncovered. Understanding the function and molecular aspects of the adaptations occurring in placental and maternal tissue's mitochondria will unveil potential targets for further therapeutic exploration that could address pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for regulating mitochondrial bioenergetics. This review will also describe the potential therapeutic use of compounds with a recognised effect on mitochondria, for the management of preeclampsia.

Role of Heat Shock Protein 70 (HSP-70) after Giving Nanoherbal Haramonting (Rhodomyrtus tomentosa) in Preeclamptic Rats.

BACKGROUND AND OBJECTIVE: Haramonting (Rhodomyrtus tomentosa) is an alternative herb to improve health because it has many biological activities and antioxidant. HSP-70 levels as biomarkers of preeclampsia affected the anti-apoptosis of damaged cells in the placenta. This study aimed to evaluate the role of HSP-70 expressions by investigating whether effect haramonting leaves in PE rats. MATERIALS AND METHODS: The study design was control (C): pregnant rats without treatment, PE: Preeclamptic rats, PE+E: PE rats were given 1 mL EVOO kg-1 b.wt./day orally (pregnancy 13-19), PE+H: PE rats were given nano herbal haramonting 100 mg kg-1 b.wt. (pregnancy 13-19 days). PE+E+H: PE rats were given EVOO 0.5 mL kg-1 b.wt. and nano herbal haramonting 50 mg kg-1 b.wt. (pregnancy 13-19 day). Surgery was performed by taking blood from the heart for the SGOT/SGPT parameters, creatinine and HSP70. RESULTS: A significant difference was observed in all groups with the value p<0.0001 and HSP-70 Expressions affect in preeclamptic rats after given this herbal. The value of SGOT, SGPT and creatinine can affect preeclamptic rats and can be as a biomarker of preeclampsia. A significant difference also in fetus weight (p<0.01) but an insignificant difference in placental weight (p>0.05). CONCLUSION: These findings indicate that Nano herbal haramonting and EVOO possess antioxidative effects and a promising drug for the future in the treatment of preeclampsia.

Effects of Nanoherbal Haramonting (Rhodomyrtus tomentosa) and Extra Virgin Olive Oil on Histology of Liver and Kidney of Preeclamptic Rats.

BACKGROUND AND OBJECTIVE: Preeclampsia (PE) is a life threatening disease prevailing in pregnant women in Indonesia. Impaired kidneys and livers function in PE has a high risk during pregnancy. This study aimed to determine the role of nanoherbal haramonting and Extra Virgin Olive Oil (EVOO) on kidney and liver safety in preeclampsia rats. Nanoherbal Rhodomyrtus tomentosa is a medicinal plant with antioxidant activity such as EVOO which acts as inhibitor of oxidation, reduces lipid peroxidation and increases the speed of epithelialization. MATERIALS AND METHODS: This study used pregnant rats (Ratus norvegicus) consisting of 5 treatments. Animal models of preeclampsia were made by injection of NaCl 6% 3 mL/day/kg b.wt., subcutaneously in pregnancy of 6-12 days and then given herbs in pregnancy at 13-19 days. The study group consisted of, C-: Normal pregnant rats, C+: PE rats, T1: PE rats were given EVOO, T2: PE rats were given nanoherbal haramonting and T3: PE rats were given EVOO and nanoherbal haramonting. Tissue histology was made by the paraffin method and staining Hematoxylin Eosin which was dissected on the 20th day of pregnancy. RESULTS: There was no significant difference in weight of the liver and kidneys after administration of EVOO and nanoherbal haramonting. The administration of this herb significantly decreased the narrowing of the kidney tubules and the glomerular diameters. Both of these herbs also repaired preeclamptic liver damage (p<0.05) in normal hepatocyte cells, parenchymal degeneration and necrosis. CONCLUSION: The EVOO and nanoherbal haramonting repaired preeclamptic liver and kidney damage.

Exploring the role of LC-PUFA metabolism in pregnancy complications.

Maternal nutrition during pregnancy plays a significant role in growth and development of the placenta and influencing pregnancy outcome. Suboptimal nutritional status during early gestational period compromises the normal course of pregnancy leading to adverse maternal and fetal outcomes. Omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFA) are important for the growth and development of the placenta. Maternal fatty acids and their metabolites influence the normal course of pregnancy by regulating cell growth and development, cell signaling, regulate angiogenesis, modulate inflammatory responses and influence various structural and functional processes. Alterations in LC-PUFA and their metabolites may result in inadequate spiral artery remodeling or placental angiogenesis leading to structural and functional deficiency of the placenta which contributes to several pregnancy complications like preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, and results in adverse birth outcomes. In this review, we summarize studies examining the role of fatty acids and their metabolites in pregnancy. We also discuss the possible molecular mechanisms through which LC-PUFA influences placental growth and development. Studies have demonstrated that omega-3 fatty acid supplementation lowers the incidence of preterm births, but its effect on reducing pregnancy complications are inconclusive.

The relationship among vitamin D, TLR4 pathway and preeclampsia.

Preeclampsia is a pregnancy-specific syndrome that has been the greatest cause of maternal and fetal morbidity and mortality. The impaired outcomes are related to maternal and the offspring healthy in the short and long-term. Although preeclampsia origins remain unclear, it is well known that there is impaired trophoblast invasion with culminant abnormal immune response. The early and late-onset preeclampsia have been studied, the subtypes have the same difference in the placentation and inflammatory features. Dietary compounds can stimulate or inhibit the activation of immune cells. Low vitamin D intake has been linked to impaired fetal development, intrauterine growth restriction, and preeclampsia. Vitamin D has been described as an anti-inflammatory effect. It can downregulate pro-inflammatory cytokines expression by the inhibition of the Nuclear Factor-ĸB pathway signaling cascade. High vitamin D levels could attenuate the immune response. On the other hand, vitamin D deficiency may contribute to increasing pro-inflammatory state. In preeclampsia, there is a reduced expression of vitamin D receptor and its metabolism is disrupted. In this review, we aimed to discuss the role of vitamin D as an anti-inflammatory agent in relation to the pro-inflammatory process of preeclampsia through the activation of the TLR4 pathway. Although there are limited studies showing the relation between vitamin D and lower risk of preeclampsia, the maternal status of vitamin D seems to influence the risk of PE development. Therefore, vitamin D supplementation in women may be a strategy to improve pregnancy outcomes.

Antibody against Na/K-ATPase Inhibitor Lowers Blood Pressure and Increases Vascular Fli1 in Experimental Preeclampsia.

BACKGROUND: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). We demonstrated that MBG induces fibrosis via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. We hypothesized that PE blockade of increased MBG with antibody would lessen the fibrosis of umbilical arteries and lower the blood pressure in rats with PE. METHODS: We tested 36 pregnant Sprague-Dawley rats in which 12 were made hypertensive by 1.8% Na supplementation (days 6-19 of gestation), 12 pregnant rats served controls. At day 19, PE rats received one intraperitoneal injection of polyclonal anti-MBG-4 antibody (0.5 ug/ml) for 4 hours. RESULTS: PE was associated with higher blood pressure (117 ± 2 vs. 107 ± 2 mm Hg; P < 0.01), plasma MBG levels (1.54 ± 0.34 vs. 0.49 ± 0.11 nmol/L; P < 0.01), protein excretion (26 vs. 12 mg/24 hours), sFlt-1 (3-fold), decrease in Fli1 (7-fold) and increase in collagen-1 in aorta (4-fold) vs. control rats (all P < 0.01). In 12 rats treated with polyclonal anti-MBG-4 antibody blood pressure dropped (93 ± 3 mm Hg) and Fli1 was decreased much less (2-fold; P < 0.01 vs. nontreated rats). CONCLUSIONS: These results demonstrate that in experimental PE elevated MBG level is implicated in umbilical fibrosis via suppression of Fli1.

Maternal omega-3 fatty acids and vitamin E improve placental angiogenesis in late-onset but not early-onset preeclampsia.

Abnormal placental vasculature is associated with preeclampsia. Preeclampsia is of two types, i.e., early- and late-onset preeclampsia (LOP), both having different etiologies. We have earlier demonstrated low levels of omega-3 fatty acids and vitamin E in women with preeclampsia. The current study examines the effect of maternal omega-3 fatty acids and vitamin E supplementation on angiogenic factors in a rat model of preeclampsia. Pregnant rats were divided into a total of five groups control, early-onset preeclampsia (EOP); LOP; EOP supplemented with omega-3 fatty acid and vitamin E and LOP supplemented with omega-3 fatty acid and vitamin E. Preeclampsia was induced by administering L-nitroarginine methylester (L-NAME) at the dose of 50 mg/kg body weight/day. The vascular endothelial growth factor gene expression and protein levels were lower (p < 0.01 for both) in animals from both EOP as well as LOP groups (p < 0.01). In the EOP group, the protein levels of VEGF receptor-1 were also lower (p < 0.01). Supplementation of omega-3 fatty acids and vitamin E to LOP improved the levels of VEGF and VEGF receptor-1 only in the LOP but not in the EOP group. In the EOP group, the gene expression of hypoxia inducible factor 1 alpha (HIF-1α) in the placenta was higher (p < 0.05) and supplementation normalized these levels. Our findings indicate that maternal supplementation of omega-3 fatty acids and vitamin E has differential effect on preeclampsia subtypes.

Colostrum of Preeclamptic Women Has a High Level of Polyphenols and Better Resistance to Oxidative Stress in Comparison to That of Healthy Women.

Preeclampsia is a common pregnancy complication. Abnormal development of the placenta is the prevailing cause theory of this complication. Women with preeclampsia suffer from acute oxidative stress and high lipid oxidation in plasma. The aim of this study was to compare levels of polyphenols and lipid peroxidation in colostrum of nursing mothers with and without preeclampsia. The study was conducted at the Department of Obstetrics and Gynecology at Soroka University Medical Center. The study group consisting of 18 women, who were diagnosed with preeclampsia, was compared to the control group: 22 healthy women. The total phenolic content in the colostrum was determined by using the Folin-Ciocalteu method. Lipid peroxidation was determined by measuring MDA, using the TBARS assay. Polyphenol concentrations were significantly higher (about 33%) in the colostrum of the study group compared with the control group (p = 0.00042). Lipid peroxidation levels (MDA) were significantly lower (about 20%) in the colostrum of the study group compared with the control group (p = 0.03). Negative correlation was found between MDA concentration and the polyphenol level (R = -0.41, p = 0.02). In conclusion, we showed in this study a potential compensation mechanism that protects the newborn of a mother with preeclampsia from the stress process experienced by its mother.

AP39, a Modulator of Mitochondrial Bioenergetics, Reduces Antiangiogenic Response and Oxidative Stress in Hypoxia-Exposed Trophoblasts: Relevance for Preeclampsia Pathogenesis.

Although the cause of preeclampsia, a pregnancy complication with significant maternal and neonatal morbidity, has not been fully characterized, placental ischemia attributable to impaired spiral artery remodeling and abnormal secretion of antiangiogenic factors are thought to be important in the pathogenesis of the disease. Placental ischemia could impair trophoblast mitochondrial function and energy production, leading to the release of reactive oxygen species (ROS). ROS have been shown to stabilize hypoxia-inducible factor (HIF)-1α, which, in turn, may induce transcription of antiangiogenic factors, soluble fms-like tyrosine kinase 1 (sFLT1), and soluble endoglin in trophoblasts. Herein, we tested whether the angiogenic imbalance and oxidative stress in the preeclamptic placenta may be prevented by improving mitochondrial function. First, to evaluate the cause-effect relationship between mitochondrial function and sFLT1 production, a human trophoblast primary cell culture model was established in which hypoxia induced mitochondrial ROS production and concurrent sFLT1 increase. Second, treatment with AP39, a novel mitochondria-targeted hydrogen sulfide donor, prevented ROS production, reduced HIF-1α protein levels, and diminished sFLT1 production. Finally, AP39, a modulator of mitochondrial bioenergetics enhanced cytochrome c oxidase activity, reversed oxidative stress and antiangiogenic response in hypoxic trophoblasts. These results suggest that placental hypoxia induces ROS production, HIF-1α stabilization, and sFLT1 up-regulation; these pathophysiological alterations can be attenuated by mitochondrial-targeted antioxidants.

Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia.

Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine whether melatonin could be a useful adjuvant therapy. In a xanthine/xanthine oxidase (X/XO) placental explant model, melatonin reduced oxidative stress (8-isoprostane) and enhanced antioxidant markers (Nrf2 translocation, HO-1), but did not affect explant production of anti-angiogenic factors (sFlt, sEng, activin A). In cultured HUVECs, melatonin mitigated TNFα-induced vascular cell adhesion molecule expression and rescued the subsequent disruption to endothelial monolayer integrity but did not affect other markers for endothelial activation and dysfunction. In a phase I trial of melatonin in 20 women with preeclampsia, we assessed the safety and efficacy of melatonin on (i) preeclampsia progression, (ii) clinical outcomes, and (iii) oxidative stress, matching outcomes with recent historical controls receiving similar care. Melatonin therapy was safe for mothers and their fetuses. Compared to controls, melatonin administration extended the mean ± SEM diagnosis to delivery interval by 6 ± 2.3 days reduced the need for increasing antihypertensive medication on days 3-4 (13% vs 71%), days 6-7 (8% vs 51%), and at delivery (26% vs 75%). All other clinical and biochemical measures of disease severity were unaffected by melatonin. We have shown that melatonin has the potential to mitigate maternal endothelial pro-oxidant injury and could therefore provide effective adjuvant therapy to extend pregnancy duration to deliver improved clinical outcomes for women with severe preeclampsia.

Placental histopathological lesions in correlation with neonatal outcome in preeclampsia with and without severe features.

OBJECTIVE: We aimed to compare pregnancy outcome and placental histopathology in women with preeclampsia (PE) with and without severe features. METHODS: The medical records and placental pathology reports of all pregnancies complicated by PE during 2008-2016, were reviewed. Results were compared between those with and without severe features (severe PE vs. mild PE groups), according to current ACOG guidelines. Placental lesions were classified to maternal/fetal vascular supply lesions, and maternal/fetal inflammatory responses. Small for gestational age (SGA) was defined as neonatal birth-weight ≤10th%. Composite adverse neonatal outcome was defined as one or more of the following: sepsis, transfusion, phototherapy, respiratory morbidity, cerebral morbidity, NEC, or death. RESULTS: The severe PE group (n = 284) was characterized by lower gestational age at delivery (p < 0.001), and higher rates of antenatal corticosteroid use (p = 0.003), and cesarean deliveries (p < 0.001) as compared to the mild PE group (n = 151). More placentas <10th% and more composite maternal vascular malperfusion (MVM) lesions were observed in the severe PE group as compared to the mild PE group (p < 0.001 for both). In multivariate analysis, composite placental MVM lesions were independently associated with severe PE (aOR = 1.75, 95%CI 1.4-4.9). Higher rates of SGA (p = 0.016), and composite adverse neonatal outcome (p = 0.002) characterized the severe PE group. In multivariate analysis, adverse neonatal outcome was independently associated with gestational age (aOR = 0.54, 95%CI 0.49-0.68), SGA (aOR = 1.75, 95%CI = 1.15-3.59), severe PE (aOR = 1.8, 95%CI = 1.13-3.54) and placental MVM lesions (aOR = 2.13, 95%CI = 1.05-4.39). CONCLUSION: More pronounced placental pathology and higher rate of adverse neonatal outcome characterize preeclampsia with severe features as compared with the milder form of the disease.

Ex Vivo Dual Perfusion of the Human Placenta: Disease Simulation, Therapeutic Pharmacokinetics and Analysis of Off-Target Effects.

In recent years ex vivo dual perfusion of the human placental lobule is seeing an international renaissance in its application to understanding fetal health and development. Here, we discuss the methods and uses of this technique in the evaluation of (1) vascular function, (2) transplacental clearance, (3) hemodynamic and oxygenation changes associated with pregnancy complications on placental structure and function, and (4) placental toxicology and post-perfusion evaluation of tissue architecture.

The Status of Biochemical and Molecular Markers of Oxidative Stress in Preeclamptic Saudi Patients.

PURPOSE: In the light of contradictory results and paucity of information, this comprehensive study examines the activities and levels of key antioxidants and oxidants/pro-oxidants in preeclamptic patients. METHODS: Antioxidants including glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase, catalase, reduced glutathione, selenium, zinc, copper and manganese, as well as marker oxidants/pro-oxidants including hydrogen peroxide, superoxide anions, malondialdehyde, protein carbonyls and oxidized glutathione were determined in plasma and placental tissues of nonpregnant, healthy pregnant and preeclamptic subjects. RESULTS: Data indicated that all plasma antioxidants underwent moderate but significant decreases (p< 0.05) in healthy pregnant women, , and much more significant ones (p< 0.0001) in preeclamptic patients, when both were compared to non-pregnant subjects. Furthermore, whereas all plasma antioxidants underwent significant decreases (p< 0.001) in preeclamptic patients compared to healthy pregnant subjects, their placental activities and levels were very significantly decreased (p< 0.0001). However, copper plasma and placental levels were unchanged in all study groups. In contrast, there were increases similar in magnitude and significance of all plasma and placental oxidants/prooxidants compared among the three study groups leading to equally significant decreases in the reduced/oxidized glutathione ratios. In addition, gene transcripts of all antioxidant enzymes underwent marked downregulation (p< 0.0001) in placental tissue of preeclamptic patients compared to healthy pregnant subjects. CONCLUSION: Data indicated a metabolic shift in favor of oxidative stress more pronounced in placental tissue of preeclamptic patients compared to healthy pregnant/non-pregnant subjects. We postulate that selenium, zinc and manganese supplements could be beneficial for alleviation of the noted oxidative stress in preeclamptic patients.

Theobroma cacao increases cells viability and reduces IL-6 and sVCAM-1 level in endothelial cells induced by plasma from preeclamptic patients.

This study aims to investigate whether an ethanolic extract of Theobroma cacao bean is able to increase cell viability and decrease IL-6 and sVCAM-1 in endothelial cells induced by plasma from preeclamptic patients. Endothelial cells were obtained from human umbilical vascular endothelial cells. At confluency, endothelial cells were divided into six groups, which included control (untreated), endothelial cells exposed to plasma from normal pregnancy, endothelial cells exposed to 2% plasma from preeclamptic patients (PP), endothelial cells exposed to PP in the presence of ethanolic extract of T. cacao (PP+TC) at the following three doses: 25, 50, and 100 ppm. The analysis was performed in silico using the Hex 8.0, LigPlus and LigandScout 3.1 software. Analysis on IL-6 and sVCAM-1 levels were done by enzyme linked immunosorbent assay (ELISA). We found that seven of them could bind to the protein NFκB (catechin, leucoanthocyanidin, niacin, phenylethylamine, theobromine, theophylline, and thiamin). This increase in IL-6 was significantly (P<0.05) attenuated by both the 50 and 100 ppm treatments of T. cacao extract. Plasma from PP significantly increased sVCAM-1 levels compared to untreated cells. This increase in sVCAM-1 was significantly attenuated by all doses of the extract. In conclusion, T. cacao extract prohibits the increase in IL-6 and sVCAM-1 in endothelial cells induced by plasma from preeclamptic patients. Therefore this may provide a herbal therapy for attenuating the endothelial dysfunction found in preeclampsia.

Health workers' knowledge on future vascular disease risk in women with pre-eclampsia in south western Nigeria.

BACKGROUND: Pre-eclampsia progressing to eclampsia is one of the major causes of maternal death in Nigeria. Since there is long term association of pre-eclampsia with cardiovascular disease, cerebrovascular disease, renal disease, short life expectancy and mortality, it is essential to obtain obstetric history for better counseling and long term monitoring. The study assessed the knowledge of health workers about the association of pre-eclampsia with future cardiovascular disease and offering any risk-reduction counseling to women with pre-eclampsia. METHODS: During a training workshop, a validated questionnaire on the association between pre-eclampsia and cardiovascular risk was distributed among health care workers working at the infant welfare and family planning clinics in Osun State. Data were analysed using descriptive and inferential statistics. RESULTS: One hundred and forty-six out of 150 health workers approached participated in the study (response rate 97.3%). Mean age of respondents was 35.6 ± 9.1 years. Median age of practice was 7 years, ranging from 1-40 years. They were medical doctors (60.3%), community health workers (26.7%) and nurses/midwives (13.0%). Most participants had good knowledge on future cardiovascular risk of pre-eclampsia. The medical doctors had better knowledge compared to nurses/midwives and community health workers (78.4 vs. 57.9 vs. 53.8%; p < 0.05). Below half (45.9%) offered risk-reduction counseling. CONCLUSION: Knowledge of the cardiovascular risk factors was lower among the nurses/midwives and community health workers. Risk reduction counseling was quite low across all the health workers. There is need for continuous medical education and possible review of the training curriculum of the lower cadres of health workers.

Effect of Docosahexaenoic Acid on Apoptosis and Proliferation in the Placenta: Preliminary Report.

INTRODUCTION: Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction (IUGR) and preeclampsia, with excessive apoptosis. One potential mechanism of action of docosahexaenoic acid (DHA) promoting a reduction in the risk of pathological pregnancy may be by influencing these processes in the placenta. MATERIALS AND METHODS: We investigated 28 pregnant women supplemented with a fish oil product containing 300 mg DHA starting from pregnancy week 20 until delivery (DHA group). The control group consisted of 50 women who did not receive such supplementation (control group). We determined the expression of Ki-67 and p21 as markers of proliferation and caspase 3 activity as a marker of apoptosis and DHA levels in umbilical cord blood. RESULTS: Caspase 3 activity was significantly lower in the DHA group in comparison to the control group. Umbilical cord blood DHA concentration was higher in the DHA group. The expression of the proteins p21 and Ki-67 did not differ significantly between the groups. CONCLUSIONS: We observed an association between DHA supplementation and inhibition of placental apoptosis. We did not find an association between DHA and proliferation process in the placenta.