Az angiogén faktorok szerepe praeeclampsiában

Preeclampsia is one of the most common and most serious complications of pregnancy and the management of this condition still challenges obstetricians. Despite intensive research the etiology of preeclampsia still remains unclear. At the beginning of the 2000s preeclampsia-related research was directed towards factors that influence angiogenesis. Most studies have been carried out on the placental growth factor and soluble fms-like tyrosine kinase-1. Most publications confirm the increased concentrations of antiangiogenic factors and decreased concentrations of proangiogenic factors in maternal blood samples in preeclampsia even before the onset of clinical symptoms. According to our current knowledge antiangiogenic proteins are responsible for the endothelial dysfunction in the symptomatic stage of the disease. Placental growth factor and soluble fms-like tyrosine kinase-1 may have important roles in the prediction and treatment of the disease. The point of care detection of placental growth factor and soluble fms-like tyrosine kinase-1 may be used to predict preeclampsia. Rapid tests are available to determine the serum levels of the two proteins. Removal of soluble fms-like tyrosine kinase-1 from maternal circulation is a potential treatment option for early onset preeclampsia. Orv. Hetil., 2014, 155(47), 1860-1866

Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study.

BACKGROUND: Hypertensive disorders of pregnancy and intrauterine growth restriction (IUGR) are leading causes of maternal and perinatal morbidity and mortality. Failure to detect intrauterine growth restriction in women at high risk has been highlighted as a significant avoidable cause of serious fetal outcome. In this observational study we compare fetal flow using Doppler ultrasonography with a new test for placental growth factor (PlGF) to predict fetal adverse events. METHODS: Eighty-nine women with hypertensive disorders of pregnancy (24 with chronic hypertension, 17 with gestational hypertension, 12 with HELLP syndrome, 19 with preeclampsia and 17 with superimposed preeclampsia) were enrolled. A single maternal blood sample to measure free PlGF (Alere Triage) taken before 35 weeks of pregnancy was compared to the last Doppler ultrasound measurement of fetal flow before delivery. PlGF was classified as normal (PlGF>/=100 pg/ml), low (12<PlGF<100) or very low (PlGF</=12 pg/ml). A positive test for abnormal fetal flow was defined as either signs of centralisation of the fetal circulation or diastolic block or reverse flow in the umbilical artery or descending aorta; this was a criterion for delivery. Fetal outcomes were intrauterine growth restriction and birth before 37 weeks of pregnancy. RESULTS: In total 61/89 women had a preterm birth and 22 infants had IUGR. Of those who delivered preterm, 20/20 women with abnormal fetal flow and 36/41 (87.8%) women with normal fetal flow had low or very low PlGF. Of those infants with IUGR, 22/22 had low or very low maternal PlGF and 10/22 had abnormal fetal flow. CONCLUSIONS: PlGF may provide useful information before 35th gestational week to identify fetuses requiring urgent delivery, and those at risk of later adverse outcomes not identified by fetal flow Doppler ultrasonography

Placental Protein 13 (PP13) – a placental immunoregulatory galectin protecting pregnancy

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure d

CB1-cannabinoid receptors are involved in the modulation of non-synaptic [3H]serotonin release from the rat hippocampus.

In the present study we investigated whether serotonin release in the hippocampus is subject to regulation via cannabinoid receptors. Both rat and mouse hippocampal slices were preincubated with [3H]serotonin ([3H]5-HT) and superfused with medium containing serotonin reuptake inhibitor citalopram hydrobromide (300 nM). The cannabinoid receptor agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55,212-2, 1 microM) did not affect either the resting or the electrically evoked [3H]5-HT release. In the presence of the ionotropic glutamate receptor antagonists D(-)-2-amino-5-phosphonopentanoic acid (AP-5, 50 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione-disodium (CNQX, 10 microM) the evoked [3H]5-HT release was decreased significantly. Similar findings were obtained when CNQX (10 microM) was applied alone with WIN55,212-2. This effect was abolished by the selective cannabinoid receptor subtype 1 (CB1) antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716, 1 microM) and 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide trifluoroacetate salt (AM251, 1 microM). Similarly to that observed in rats, WIN55,212-2 (1 microM) decreased the evoked [3H]5-HT efflux in wild-type mice (CB1+/+). The inhibitory effect of WIN55,212-2 (1 microM) was completely absent in hippocampal slices derived from mice genetically deficient in CB1 cannabinoid receptors (CB1-/-). Relatively selective degeneration of fine serotonergic axons by the neurotoxin parachloramphetamine (PCA) reduced significantly the tritium uptake and the evoked [3H]5-HT release. In addition, PCA, eliminated the effect of WIN55,212-2 (1 microM) on the stimulation-evoked [3H]5-HT efflux. In contrast to the PCA-treated animals, WIN55,212-2 (1 microM) reduced the [3H]5-HT efflux in the saline-treated group. Our data suggest that a subpopulation of non-synaptic serotonergic afferents express CB1 receptors and activation of these CB1 receptors leads to a decrease in 5-HT release.In VitroJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Biomarkers and the prediction of adverse Ooutcomes in preeclampsia: a systematic review and meta-analysis

To systematically review the performance of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio in predicting adverse outcomes in women with preeclampsia.Data sourcesWe performed a systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, Scopus, ClinicalTrials.gov, and Emcare databases from 1989 to March 2019 to identify studies correlating sFlt-1, PlGF, and the sFlt-1/PlGF ratio with the occurrence of adverse outcomes in women with preeclampsia.Methods of study selectionTwo independent reviewers screened 3,194 studies using Covidence. Studies were included if they examined the performance of sFLT-1, PlGF, or the sFLT-1/PlGF ratio in predicting adverse outcomes in women with suspected or confirmed preeclampsia.Tabulation, integration, and resultsWe extracted contingency tables with true-positive, false-positive, true-negative, and false-negative results. We calculated sensitivity, specificity, diagnostic odds ratios, and area under the summary receiver operating characteristic curve (area sROC) through a bivariate mixed-effects meta-analysis. Our literature search identified 3,194 articles, of which 33 (n=9,426 patients) were included. There was significant variation in the included studies with regard to the biomarkers and outcomes assessed. As such, few studies (n=4-8) were included in the meta-analysis component with significant heterogeneity between studies (I2=33-99). Nonetheless, both PlGF and the sFlt-1/PlGF ratio demonstrated area sROC values between 0.68 and 0.87 for the prediction of composite adverse maternal and perinatal outcomes, preterm birth and fetal growth restriction.ConclusionPlacental growth factor and the sFlt-1/PlGF ratio show prognostic promise for adverse outcomes in preeclampsia, but study heterogeneity limits their clinical utility.Sean Lim, Wentao Li, Jessica Kemper, Andrew Nguyen, Ben Willem Mol, Maya Redd