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soluble tyrosine kinase 1

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https://www.readbyqxmd.com/read/29749110/metformin-for-the-prevention-of-hypertensive-disorders-of-pregnancy-in-women-with-gestational-diabetes-and-obesity-a-systematic-review-and-meta-analysis
#1
REVIEW
Erkan Kalafat, Yavuz Emre Sukur, Abdulkadir, Basky Thilaganathan, Asma Khalil
OBJECTIVES: Metformin has been reported to reduce the risk of preeclampsia. It is also known to influence soluble fms-like tyrosine kinase-1 (sFlt-1) levels, which correlate significantly with the gestation of onset and severity of preeclampsia. The main aim of this systematic review and meta-analysis was to determine whether metformin use is associated with the incidence of hypertensive disorders of pregnancy (HDP). METHODS: MEDLINE (1947 - September 2017), Scopus (1970 - September 2017) and the Cochrane Library (since inception - September 2017) were searched for relevant citations in English language...
May 10, 2018: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29748248/bromodomain-protein-brd4-is-increased-in-human-placentas-from-women-with-early-onset-preeclampsia
#2
Stella Liong, Gillian Barker, Martha Lappas
Preeclampsia affects 5% of all pregnancies and is a serious disorder of pregnancy, characterised by high maternal blood pressure, placental hypoxia, fluid retention (oedema) and proteinuria. Women with preeclampsia are associated with exaggerated levels of pro-inflammatory cytokines, chemokines and anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFLT1). Studies in non-gestational tissues have described the bromodomain (BRD) and extraterminal family of proteins, in particular BRD4 to play a critical role in propagating inflammation and is currently a therapeutic target for treating cancer, lung inflammation and asthma...
June 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29739809/application-of-physiologically-based-pharmacokinetic-modeling-in-understanding-bosutinib-drug-drug-interactions-importance-of-intestinal-p-glycoprotein
#3
Shinji Yamazaki, Cho-Ming Loi, Emi Kimoto, Chester Costales, Manthena V Varma
Bosutinib is an orally available Src/Abl tyrosine kinase inhibitor indicated for the treatment of patients with Ph+ chronic myelogenous leukemia at a clinically recommended dose of 500 mg once daily. Clinical results indicated that increases in bosutinib oral exposures were supra-proportional at the lower doses (50 to 200 mg) and approximately dose-proportional at the higher doses (200 to 600 mg). Bosutinib is a substrate of CYP3A4 and P-glycoprotein and exhibits pH-dependent solubility with moderate intestinal permeability...
May 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29739273/angiogenic-dysregulation-in-pregnancy-related-hypertension-a-role-for-metformin
#4
Nerolen Soobryan, Saravanakumar Murugesan, Arunagiri Pandiyan, Jagidesa Moodley, Irene Mackraj
In the face of escalating maternal and fetal health threats, hypertensive pregnancy disorders (HPDs) is one of the leading cause of maternal and fetal morbidity and mortality. The range of HPDs include white-coat hypertension, chronic hypertension, gestational hypertension, mild-to-moderate and severe preeclampsia and eclampsia. Current evidence implicates an imbalance of circulating anti- and angiogenic factors in HPDs emanating from the placental vasculature, impacting on angiogenesis. Delivery of the fetus is thus far the only curative measure, albeit with increased risk...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29718107/the-intervention-effect-of-aspirin-on-a-lipopolysaccharide-induced-preeclampsia-like-mouse-model-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway
#5
Guanlin Li, Liyang Ma, Li Lin, Yan-Ling Wang, Huixia Yang
Preeclampsia is a severe pregnancy-related disorder, and patients usually present with high circulating inflammatory factor production as well as excessive activation of the nuclear factor-κB (NF-κB) pathway. Administration of aspirin (ASP) is effective for the prevention of preeclampsia, we proposed that ASP might affect placental function by regulating the NF-κB pathway. Systemic lipopolysaccharide (LPS) (20 μg/kg) was used to induce preeclampsia-like pregnant mouse model and low-dose ASP (15.2 mg/kg) were further treated...
April 27, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29716747/mechanisms-of-the-effect-of-magnesium-salts-in-preeclampsia
#6
Delia I Chiarello, Reinaldo Marín, Fulgencio Proverbio, Paula Coronado, Fernando Toledo, Rocio Salsoso, Jaime Gutiérrez, Luis Sobrevia
Preeclampsia is a heterogeneous pregnancy-specific syndrome associated with abnormal trophoblast invasion and endothelial dysfunction. Magnesium (Mg2+ ) level may be normal or decreased in women with preeclampsia. However, the use of Mg2+ salts, such as Mg2+ sulphate, are useful in reducing the pathophysiological consequences of preeclampsia with severe features and eclampsia. Although the mechanism of action of this Mg2+ salt is not well understood, the available evidence suggests a beneficial effect of Mg2+ for the mother and foetus...
April 24, 2018: Placenta
https://www.readbyqxmd.com/read/29709439/vasodilator-effects-and-putative-guanylyl-cyclase-stimulation-by-2-nitro-1-phenylethanone-and-2-nitro-2-phenyl-propane-1-3-diol-on-rat-aorta
#7
Thiago Brasileiro de Vasconcelos, Helder Veras Ribeiro Filho, Saad Lahlou, José Geraldo de Carvalho Pereira, Paulo Sérgio Lopes de Oliveira, Pedro Jorge Caldas Magalhães
Compounds containing a nitro group may reveal vasodilator properties. Several nitro compounds have a NO2 group in a short aliphatic chain connected to an aromatic group. In this study, we evaluated in rat aorta the effects of two nitro compounds, with emphasis on a putative recruitment of a soluble guanylate cyclase (sGC) pathway to induce vasodilation. Isolated aortic rings were obtained from male Wistar rats to compare the effects induced by 2-nitro-1-phenylethanone (NPeth) or 2-nitro-2-phenyl-propane-1,3-diol (NPprop)...
April 27, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29708884/serum-sflt-1-plgf-ratio-has-better-diagnostic-ability-in-early-compared-to-late-onset-pre-eclampsia
#8
Theng Theng Chuah, Wan Shi Tey, Mor Jack Ng, Edward T H Tan, Bernard Chern, Kok Hian Tan
BACKGROUND: To establish gestational specific cutoffs for the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio as a diagnostic tool for pre-eclampsia (PE) in an Asian population. METHODS: 82 subjects (48 PE patients and 34 controls) were recruited. sFlt-1 and PlGF were analysed on the Roche Cobas e411 analyzer and their ratio was calculated. Diagnostic performance was evaluated using receiver-operating characteristics (ROC) curves...
April 28, 2018: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/29702562/positive-and-negative-regulation-of-angiogenesis-by-soluble-vascular-endothelial-growth-factor-receptor-1
#9
REVIEW
Cristina M Failla, Miriam Carbo, Veronica Morea
Vascular endothelial growth factor receptor (VEGFR)-1 exists in different forms, derived from alternative splicing of the same gene. In addition to the transmembrane form, endothelial cells produce a soluble VEGFR-1 (sVEGFR-1) isoform, whereas non-endothelial cells produce both sVEGFR-1 and a different soluble molecule, known as soluble fms-like tyrosine kinase (sFlt)1-14. By binding members of the vascular endothelial growth factor (VEGF) family, the soluble forms reduce the amounts of VEGFs available for the interaction with their transmembrane receptors, thereby negatively regulating VEGFR-mediated signaling...
April 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29694830/celastrol-attenuates-symptoms-of-preeclampsia-in-rats-by-inhibiting-matrix-metalloproteinase-9
#10
Sha Xiao, Ming Zhang, Zhenzhen He, Deling Wang
Preeclampsia is reported in pregnant women around the world and often causes maternal/fetal mortality and morbidity. In the current study, we assessed the efficacy of celastrol on a rat preeclampsia model induced by Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME). Pregnant rats were administered L-NAME to establish preeclampsia. A total of 48 animals were randomly assigned into 4 groups (n=12 each): control, control plus celastrol treatment (control+celastrol), preeclampsia, and preeclampsia plus celastrol...
April 22, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29689494/angiogenic-factors-in-pregnancies-of-women-with-antiphospholipid-syndrome-and-systemic-lupus-erythematosus
#11
Karoline Mayer-Pickel, Christina Stern, Katharina Eberhard, Uwe Lang, Barbara Obermayer-Pietsch, Mila Cervar-Zivkovic
OBJECTIVES: An imbalance of angiogenic placental factors such as endoglin, soluble fms-like tyrosine kinase 1(sFlt-1) and placental growth factor (PlGF) has been implicated in the pathophysiology of preeclampsia. This study aimed to evaluate serum levels of sFlt-1, PlGF and endoglin in women with primary and secondary antiphospholipid Syndrome (APS) and systemic lupus erythematosus (SLE) longitudinally through pregnancy. MATERIAL AND METHODS: Serum levels of sFlt-1, PlGF and endoglin were measured prospectively at 4-week intervals (from gestational weeks 12-36) in 17 women with primary APS (PAPS), 18 women with secondary APS (SAPS), and 23 women with SLE...
April 18, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29686016/neurofilament-as-neuronal-injury-blood-marker-in-preeclampsia
#12
Katrina Suzanne Evers, Andrew Atkinson, Christian Barro, Urs Fisch, Marc Pfister, Evelyn A Huhn, Olav Lapaire, Jens Kuhle, Sven Wellmann
Preeclampsia has been shown to be associated with changes in cerebral structure and cognitive function later in life. Nf (neurofilaments) are specific scaffolding proteins of neurons, and their quantification in serum has been proposed as a biomarker for neuroaxonal injury. We performed a prospective, longitudinal, single-center study at the University Hospital of Basel to determine serum Nf concentrations in pregnant women with singleton pregnancies and with high risk of preeclampsia or with early signs of preeclampsia...
April 23, 2018: Hypertension
https://www.readbyqxmd.com/read/29683202/placental-inflammation-in-pre-eclampsia-by-nod-like-receptor-protein-nlrp-3-inflammasome-activation-in-trophoblasts
#13
G S Stødle, G B Silva, L H Tangerås, L M Gierman, I Nervik, U E Dahlberg, C Sun, M H Aune, L C V Thomsen, L Bjørge, A-C Iversen
Pre-eclampsia is associated with increased levels of cholesterol and uric acid and an inflamed placenta expressing danger-sensing pattern recognition receptors (PRRs). Crystalline cholesterol and uric acid activate the PRR Nod-like receptor protein (NLRP)3 inflammasome to release interleukin (IL)-1β and result in vigorous inflammation. We aimed to characterize crystal-induced NLRP3 activation in placental inflammation and examine its role in pre-eclampsia. We confirmed that serum total cholesterol and uric acid were elevated in pre-eclamptic compared to healthy pregnancies and correlated positively to high sensitivity C-reactive protein (hsCRP) and the pre-eclampsia marker soluble fms-like tyrosine kinase-1 (sFlt-1)...
April 23, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29674208/increased-serum-levels-of-sflt-1-plgf-ratio-in-preeclamptic-women-with-onset-at-32-weeks-compared-with-%C3%A2-32-weeks
#14
Hirotada Suzuki, Chikako Hirashima, Shiho Nagayama, Kayo Takahashi, Tatsuo Yamamoto, Shigeki Matsubara, Akihide Ohkuchi
OBJECTIVE: Our first aim was to construct gestational-age-specific reference ranges of serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio at 19-38 weeks of gestation. Our second aim was to compare the serum levels of sFlt-1, PlGF, and the sFlt-1/PlGF ratio in 81 women with PE which occurred at <32, 32-33, 34-35, and ≥36 weeks. METHOD: Serum levels of sFlt-1 and PlGF were measured by automated immunoassays (Elecsys sFlt-1 and Elecsys PlGF)...
March 19, 2018: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29674192/predictive-value-of-sflt-1-plgf-sflt-1-plgf-ratio-and-papp-a-for-late-onset-preeclampsia-and-iugr-between-32-and-37-weeks-of-pregnancy
#15
C Birdir, L Droste, L Fox, M Frank, J Fryze, A Enekwe, A Köninger, R Kimmig, B Schmidt, A Gellhaus
OBJECTIVES: The aim of this study was to investigate, whether maternal serum levels of sFlt-1, PlGF and PAPP-A at third trimester of pregnancy are associated with late-onset PE and intrauterine growth retardation (IUGR) after 34 weeks of pregnancy. METHODS: This was a prospective study measuring the maternal serum levels of soluble tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 32-37 weeks of pregnancy: 730 patients were enrolled and 676 had neither intrauterine growth restriction (IUGR) nor preeclampsia (PE) or pregnancy induced hypertension (PIH) throughout the pregnancy...
April 11, 2018: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29668708/dectin-1-2-induced-autocrine-pge2-signaling-licenses-dendritic-cells-to-prime-th2-responses
#16
Maria M M Kaisar, Manuel Ritter, Carlos Del Fresno, Hulda S Jónasdóttir, Alwin J van der Ham, Leonard R Pelgrom, Gabriele Schramm, Laura E Layland, David Sancho, Clarissa Prazeres da Costa, Martin Giera, Maria Yazdanbakhsh, Bart Everts
The molecular mechanisms through which dendritic cells (DCs) prime T helper 2 (Th2) responses, including those elicited by parasitic helminths, remain incompletely understood. Here, we report that soluble egg antigen (SEA) from Schistosoma mansoni, which is well known to drive potent Th2 responses, triggers DCs to produce prostaglandin E2 (PGE2), which subsequently-in an autocrine manner-induces OX40 ligand (OX40L) expression to license these DCs to drive Th2 responses. Mechanistically, SEA was found to promote PGE2 synthesis through Dectin-1 and Dectin-2, and via a downstream signaling cascade involving spleen tyrosine kinase (Syk), extracellular signal-regulated kinase (ERK), cytosolic phospholipase A2 (cPLA2), and cyclooxygenase 1 and 2 (COX-1 and COX-2)...
April 18, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29629873/a-maternally-sequestered-biopolymer-stabilized-vascular-endothelial-growth-factor-vegf-chimera-for-treatment-of-preeclampsia
#17
Omar C Logue, Fakhri Mahdi, Heather Chapman, Eric M George, Gene L Bidwell
BACKGROUND: Preeclampsia is a hypertensive syndrome that complicates 3% to 5% of pregnancies in the United States. Preeclampsia originates from an improperly vascularized and ischemic placenta that releases factors that drive systemic pathophysiology. One of these factors, soluble fms-like tyrosine kinase-1, is believed to sequester vascular endothelial growth factor (VEGF), leading to systemic endothelial dysfunction and hypertension. With the goal of targeting soluble fms-like tyrosine kinase-1 while simultaneously preventing fetal exposure to VEGF, we fused VEGF to elastin-like polypeptide, a biopolymer carrier that does not cross the placental barrier (ELP-VEGF)...
December 8, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29610266/causative-effects-of-genetically-determined-high-maternal-fetal-endothelin-1-on-preeclampsia-like-conditions-in-mice
#18
Feng Li, Masao Kakoki, Marcela Smid, Kim Boggess, Jennifer Wilder, Sylvia Hiller, Carol Bounajim, Scott E Parnell, Kathleen K Sulik, Oliver Smithies, Nobuyo Maeda-Smithies
Endothelin-1 (ET-1) is implicated in the pathophysiology of preeclampsia. An association between an EDN1 gene polymorphism with high ET-1 and preeclampsia was reported in humans, but their cause and effect relationships have not been defined. We examined the pregnancy effects in mice with a modified Edn1 allele that increases mRNA stability and thus ET-1 production. Heterozygous Edn1 H/ + females showed no obvious abnormalities before pregnancy, but when mated with wild-type (WT) males developed a full spectrum of preeclampsia-like phenotypes, including increased systolic blood pressure, proteinuria, glomerular endotheliosis, and intrauterine fetal growth restriction...
May 2018: Hypertension
https://www.readbyqxmd.com/read/29569955/placental-growth-factor-reverses-decreased-vascular-and-uteroplacental-mmp-2-and-9-and-increased-mmp-1-and-7-and-collagen-i-and-iv-in-hypertensive-pregnancy
#19
Zongli Ren, Ning Cui, Minglin Zhu, Raouf A Khalil
Preeclampsia is a complication of pregnancy manifested as maternal hypertension (HTN-Preg) and fetal growth restriction (IUGR), with unclear mechanism. Placental ischemia increases antiangiogenic soluble fms-like tyrosine-kinase-1 (sFlt-1) relative to angiogenic placental-growth-factor (PlGF); however, the molecular targets are unclear. To test the hypothesis that placental ischemia-induced changes in sFlt-1 and PlGF target vascular and uteroplacental matrix metalloproteinases (MMPs), we tested if raising sFlt-1/PlGF ratio by infusing sFlt-1 (10 µg/kg/day) in pregnant (Preg) rats increases blood pressure (BP) and alters MMPs, and if correcting sFlt-1/PlGF by infusing PlGF (20 µg/kg/day) in Preg rats with reduced uterine perfusion pressure (RUPP) improves BP and reverses the changes in MMPs...
March 23, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29568742/therapeutic-effect-of-long-term-epidural-block-in-rats-with-pregnancy-induced-hypertension
#20
Nianjiao Han, Yang Li, Youjing Dong
Background: Pregnancy induced hypertension (PIH) causes a variety of systemic disorders that negatively affect the maternal placenta and fetal growth. Epidural sympathetic block elicits symptoms of decreased blood pressure. This study was designed to determine the therapeutic effect of long-term epidural block in rats with PIH. Methods: Forty healthy pregnant Sprague Dawley rats were randomized into four groups with each group consisting of 10 rats. On gestation day (GD) 14, rats in control group underwent a sham procedure; rats in RUPP group were operated on to obtain reduced uterine perfusion pressure (RUPP); rats in RUPP plus normal saline (NS) group were also subjected to the RUPP procedure and underwent epidural block with 25  μ l normal saline twice daily until delivery; rats in RUPP plus epidural block (EB) group were treated as those in RUPP plus NS group except that an epidural block with 25  μ l of 0...
2018: BioMed Research International
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