Publications by authors named "Pecks U"

65 Publications

2D Versus 3D in Laparoscopic Surgery by Beginners and Experts: A Randomized Controlled Trial on a Pelvitrainer in Objectively Graded Surgical Steps.

J Surg Educ 2017 Sep - Oct;74(5):867-877. Epub 2017 Feb 16.

Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein Campus Kiel, Kiel, Germany. Electronic address:

Background And Objective: Progress in endoscopic surgery in the past few decades has led to the application of 3-dimensional (3D) procedures in operating rooms. This permits patient- and surgeon-friendly operations and also maximizes the superiority of laparoscopy over laparotomy. In this study, we compare 2-dimensional (2D) and 3D endoscopy techniques with regard to time, efficiency, optics, and handling by users with different degrees of experience at 4 difficulty levels.

Design: A randomized controlled trial on a pelvitrainer in objectively graded surgical steps for students and postgraduates.

Setting: The trials took place at the Kiel School of Gynaecological Endoscopy, a training unit of the Kiel University Department of Obstetrics and Gynecology, a tertiary academic medical center.

Participants: The 277 study participants, divided into students, residents, and specialists, worked on pelvitrainers with 2 different optical systems, the 2D full HD and the 3D mode. The following 4 exercises were performed with each optical system: (1) grasping and transferring of pins, (2) cutting predetermined marks, (3) vaginal closure with prevention of prolapse, and (4) sacrocolpopexy. The duration and success of the tasks were measured and compared. A self-assessment questionnaire was completed by the participants.

Results: Overall, the 3D-system permitted a greater improvement in working speed, superior optical visualization, and better endoscopic handling in all groups, independent of surgical experience. All students improved in speed (exercises: 1-3) and made significantly fewer mistakes (exercise 2) on 3D compared with 2D. Residents made progress in time (exercises: 1-4) and task performance (exercise 3). Specialists improved significantly in the more challenging tasks 3 and 4. Subjectively, 68.8% of participants preferred 3D for performing laparoscopy.

Conclusion: Systematic training programs on pelvitrainers can improve endoscopic skills not only in beginners but also in experienced surgeons. The 3D system offered distinct advantages over 2D imaging and was well accepted by surgeons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsurg.2017.01.011DOI Listing
June 2018

Serum cholesterol acceptor capacity in intrauterine growth restricted fetuses.

J Perinat Med 2017 Oct;45(7):829-835

.

Aim: Intrauterine growth restriction (IUGR) is an independent risk factor for the development of cardiovascular diseases later in life. The mechanisms whereby slowed intrauterine growth confers vascular risk are not clearly established. In general, a disturbed cholesterol efflux has been linked to atherosclerosis. The capacity of serum to accept cholesterol has been repeatedly evaluated in clinical studies by the use of macrophage-based cholesterol efflux assays and, if disturbed, precedes atherosclerotic diseases years before the clinical diagnosis. We now hypothesized that circulating cholesterol acceptors in IUGR sera specifically interfere with cholesterol transport mechanisms leading to diminished cholesterol efflux.

Methods: RAW264.7 cells were used to determine efflux of [3H]-cholesterol in response to [umbilical cord serum (IUGR), n=20; controls (CTRL), n=20].

Results: Cholesterol efflux was lower in IUGR as compared to controls [controls: mean 7.7% fractional [3H]-cholesterol efflux, standard deviation (SD)=0.98; IUGR: mean 6.3%, SD=0.79; P<0.0001]. Values strongly correlated to HDL (ρ=0.655, P<0.0001) and apoE (ρ=0.510, P=0.0008), and mildly to apoA1 (ρ=0.3926, P=0.0122) concentrations.

Conclusions: Reduced cholesterol efflux in IUGR could account for the enhanced risk of developing cardiovascular diseases later in life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpm-2016-0270DOI Listing
October 2017

Size Does Not Make the Difference: 3D/4D Transperineal Sonographic Measurements of the Female Urethra in the Assessment of Urinary Incontinence Subtypes.

Biomed Res Int 2016 21;2016:1810352. Epub 2016 Nov 21.

Clinic for Gynaecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.

The objective was to evaluate the usefulness of transperineal ultrasound in the assessment of the urethral length and urethral lumen by 3D/4D transperineal sonography to discriminate between female patients with subtypes of urinary incontinence. A total of 150 female patients underwent an examination because of urinary incontinence. 41 patients were diagnosed with urgency urinary incontinence (OAB), 67 patients were diagnosed with stress urinary incontinence (SUI), and 42 patients were in the control group (CTRL). Three diameters of the urethral lumen (proximal (U1), medial (U2), and distal (U3)) and the urethral length were measured. By the assessment of the urethral lumen, the presence of the urethral funneling was evaluated. We found a significant difference in the urethral length and urethral lumen U2 of OAB and SUI versus CTRL. The urethral length was significantly greater ( < 0.05) and the urethral lumen was significantly wider ( < 0.05) in the patients with urinary incontinence. The incidence of the urethral funneling was significantly higher ( < 0.05) in the study groups with urinary incontinence than in the control group. Our results have shown the urethral changes obtained by ultrasound in patients with urinary incontinence, but they are still insufficient to distinguish between subtypes of urinary incontinence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/1810352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136624PMC
February 2017

Fetal gender and gestational age differentially affect PCSK9 levels in intrauterine growth restriction.

Lipids Health Dis 2016 Nov 14;15(1):193. Epub 2016 Nov 14.

Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Kiel, Germany.

Background: Maternal and fetal Low Density Lipoprotein-Cholesterol (LDL-C) concentrations are compromised in intrauterine growth restriction (IUGR). Generally, LDL-C catabolism is under control of PCSK9 by binding to the LDL-receptor leading to its degradation. Hence, we hypothesized a role for PCSK9 in the modulation of lipid metabolism and placental transport in IUGR.

Methods: 172 women, 70 IUGR and 102 controls were included in the study. Maternal and fetal serum PCSK9 levels and lipid profiles including LDL-C were measured. Placental LDL-receptor and PCSK9 expressions were estimated by tissue microarray immunohistochemistry, and analyzed by two blinded observers using an immunoreactivity score. Non-parametric tests and multivariate regression analyses were used for statistical estimations.

Results: PCSK9 levels in the maternal and fetal compartment independently predicted LDL-C levels (maternal compartment: adjusted R  = 0.2526; coefficient b  = 0.0938, standard error s =0.0217, r = 0.4420, t-value = 4.323, p < 0.0001; fetal compartment: adjusted R  = 0.2929; b  = 0.1156, s =0.020, r = 0.5494, t-value = 5.81, p < 0.0001). We did not find significant differences in maternal PCSK9 concentrations between IUGR and controls. However, we found lower fetal serum PCSK9 concentrations in IUGR than in controls (IUGR median 137.1 ng/mL (95% CI 94.8-160.0) vs. controls 176.8 (154.6-202.5), p = 0.0005). When subgrouping according to early onset, late onset IUGR, and fetal gender differences remained consistent only for male neonates born before 34 weeks of gestation. In the placenta we found no correlation between PCSK9 and LDL-receptor expression patterns. However, the LDL-receptor was significantly upregulated in IUGR when compared to controls (p = 0.0063).

Conclusions: Our results suggest that PCSK9 play a role in impaired fetal growth by controlling fetal LDL-C metabolism, which seems to be dependent on gestational age and fetal gender. This underlines the need to identify subgroups of IUGR that may benefit from individualized and gender-specific pharmacotherapy in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-016-0365-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109703PMC
November 2016

Endoscopic removal of a retained surgical sponge in a young Syrian refugee after Caesarean section: a case report with discussion of cultural and political consequences.

Patient Saf Surg 2016 26;10:22. Epub 2016 Oct 26.

Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus 24, 24105 Kiel, Germany.

Background: Inadvertently retained sponges and instruments still constitute a major but preventable complication in surgery. Given the high geographic mobility of patients, the fluctuation of physician-patient contact, and communication problems due to language barriers, the conscientious use of structured safety protocols in clinical routine is an essential aspect of quality in health care.

Case Presentation: We report the case of a 24-year-old refugee from Syria who presented at our gynecological outpatient department with a tumor in the lower abdomen, suspected to be a lump in the ovary or the uterus. Language barriers hindered exact recording of the patient's medical history. We knew she had undergone three Caesarean sections several years ago. The diagnostic laparoscopy unexpectedly revealed a tumor suspected to be a retained surgical sponge. The lesion was removed completely and the patient discharged from the clinic five days later.

Conclusion: In ambiguous cases, the diagnostic and therapeutic potential of minimally invasive surgery ensures safe and effective treatment of the patient, a short hospital stay, and low rates of complications. Especially in cases of language and/or cultural barriers, structured safety protocols should be a part of clinical routine in order to prevent unnecessary complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13037-016-0111-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080713PMC
October 2016

Proteoform profiling of peripheral blood serum proteins from pregnant women provides a molecular IUGR signature.

J Proteomics 2016 10 22;149:44-52. Epub 2016 Apr 22.

Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Schillingallee, Germany. Electronic address:

Intrauterine growth restriction (IUGR) is an important cause of perinatal morbidity and mortality and contributes substantially to medically indicated preterm birth; preventing fetal death. Molecular profiling of the mothers' peripheral blood was desired to monitor the health conditions of the fetuses. To develop such a minimally invasive assay, we applied a protein affinity fractionation method to peripheral blood serum samples from pregnant women belonging to either the IUGR or to the control group. Proof-of-principle was shown by relative quantitation analysis of mixtures of intact proteoforms using MALDI-ToF mass spectrometry. The two best differentiating proteins and proteoforms, respectively, were apolipoprotein C-II and apolipoprotein C-III. Together with three robustly expressed protein proteoforms proapolipoprotein C-II, apolipoprotein C-III, and apolipoprotein C-III, which served as landmarks for relative quantitation analysis, they constituted the maternal IUGR proteome signature. Separation confidence of our IUGR proteoform signature reached a sensitivity of 0.73 and a specificity of 0.87 with an area under curve of 0.86 in receiver operator characteristics.

Significance: Identification of IUGR newborns in the case room is required as children are severely diseased and need specialized care during infancy. Yet, at time of birth there is no readily applicable clinical test available. Hence, a molecular profiling assay is highly desired. It needs to be mentioned that current clinical definitions and recommendations for IUGR are unfortunately misleading and are not universally applicable. The most commonly adopted definition is an abdominal circumference (AC) or estimated fetal weight measurement <10th percentile. Although both, the American College of Obstetricians and Gynecologists (ACOG) and the Royal College of Obstetricians and Gynecologists (RCOG) agree that at this cut-off the risk of perinatal morbidity and mortality increases, this definition does not take into account the individualized growth potential of each fetus. In particular its sole use fails to identify larger fetuses that have not achieved their growth potential and may be at risk of adverse outcomes. Also, this definition, when solely applied, will result in the misdiagnosis of IUGR for some constitutionally small fetuses. It needs to be pointed out that the above mentioned criteria can only be determined during pregnancy in case mothers report from early on during pregnancy. We have developed a test that relies on mass spectrometric analysis of the mother's serum protein composition (IUGR signature) which can be determined just ahead of delivery and at date of delivery, respectively using a minimal invasive blood sampling approach. With this manuscript we describe the use of a mass spectrometric profiling method of 30 peripheral blood samples from pregnant women prior to giving birth of either unsuspicious newborns or IUGR-affected infants. We report for the first time that maternal blood sample analysis via affinity mass spectrometry differentiates IUGR infants from controls with high confidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jprot.2016.04.027DOI Listing
October 2016

The effects of Nrf2 deletion on placental morphology and exchange capacity in the mouse.

J Matern Fetal Neonatal Med 2017 Sep 3;30(17):2068-2073. Epub 2016 Oct 3.

a Department of Anatomy and Cell Biology , RWTH Aachen University Hospital , Aachen , Germany.

Objectives: Intrauterine growth restriction (IUGR) is defined as a pathological decreased fetal growth. Oxidative stress has been connected to the restriction in the fetal growth. The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is a potent activator of the cellular antioxidant response. The effect Nrf2 on fetal-placental development has not yet been sufficiently investigated. Here, we evaluated the placental and fetal growth in Nrf2 knockout (Nrf2-KO) and Nrf2-wild type mice (Nrf2-WT) throughout pregnancy.

Methods: Heterozygote Nrf2 (Nrf2) mice were paired to get Nrf2-KO and Nrf2-WT in the litters. Placentae and embryos from both genotypes were collected and weighed on days 13.5, 15.5 and 18.5 post coitum. The absolute volumes of the labyrinth zone and the total volume of the placenta were determined using the Cavalieri principle.

Results: On E 18.5 the fetal weight in Nrf2-KO was significantly reduced versus Nrf2-WT indicating a decrease in placental efficiency. A significant reduction in both total and labyrinth-volume in the placenta of Nrf2-KO mice was observed.

Conclusion: This data points out the necessity of functional Nrf2 for fetal and placental growth. A deficiency in Nrf2 signaling may negatively affect nutrient transfer capacity which is then no longer able to meet fetal growth demands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2016.1236251DOI Listing
September 2017

Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies.

Geburtshilfe Frauenheilkd 2016 Jul;76(7):799-808

Department of Nephrology, Hypertension and Clinical Pharmacology and Department of Clinical Research, Inselspital University Hospital Bern, Bern, Switzerland.

Objective: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies.

Methods: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations.

Results: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = - 0.47, ρ = - 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR.

Discussion: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the changes were most obvious in pregnancies complicated by IUGR and only minor changes were observed in pregnancies where patients had impaired liver function, our data suggests that placental rather than maternal hepatic function strongly determines lipid and steroid levels in pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0042-107078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001571PMC
July 2016

[Influences on Placental Growth Factor (PlGF) and Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Concentration Levels at the Time of First Trimester Screening].

Z Geburtshilfe Neonatol 2016 Aug 2;220(4):166-72. Epub 2016 May 2.

Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel.

Introduction: The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are significantly altered in preeclampsia with elevated sFlt-1 levels and low PlGF in the continuation of pregnancies. Furthermore, patients with preeclampsia reveal significantly low PlGF levels in the first trimester.

Material And Method: We performed a retrospective study including 161 patients during the first trimester screening between 11+0 and 13+6 weeks of gestation. In addition, we analyzed sFlt-1 und PlGF in maternal serum with a Roche Elecsys(®) System.

Results: The mean values for sFlt-1 were 1 247,11±545,84 pg/ml and 47,00±22,62 pg/ml for PlGF. There is a positive correlation between sFlt-1 and PAPP-A MoM (rS=0,681, p<0,001), and PlGF and PAPP-A MoM (rS=0,465, p<0,001), respectively. There was a negative correlation between sFlt-1 and maternal body mass index (rS=-0,225, p=0,005). Overweight patients had significantly lower sFlt-1 values than patients with normal weight (p=0,003). PlGF and the crown-rump-length of the fetus showed a positive correlation (rS=0,27, p<0,001), whereas PlGF and the Pulsatility Index of the uterine arteries were negative correlated (rS=-0,235; p=0,012). Patients with a preexistent diabetes mellitus had significantly low sFlt-1 und PlGF (p<0,05) values. Smokers had significantly elevated PlGF-values (p<0,001).

Conclusion: sFlt-1 and PlGF are influenced by various factors during the first trimester of pregnancy which can be relevant for correct interpretation. Further prospective studies may be necessary to validate our results. The aim should be to establish sFlt-1 and PlGF MoM values to allow for integration into a screening for preeclampsia in the first trimester.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0042-104801DOI Listing
August 2016

Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer.

J Transl Med 2015 May 7;13:146. Epub 2015 May 7.

Department of Gynecology and Obstetrics, University Medical Center RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.

Background: Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells' increased demands for membrane, energy, and protein production.

Methods: We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition's impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and (18) F-fluoromethylcholine uptake measurement, respectively.

Results: Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold-100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin's half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower (18) F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy.

Conclusions: FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-015-0511-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504229PMC
May 2015

Off-label use of misoprostol for labor induction in Germany: a national survey.

Eur J Obstet Gynecol Reprod Biol 2015 Apr 12;187:85-9. Epub 2014 Dec 12.

Faculty of Medicine, Gynaecology and Obstetrics, RWTH Aachen University Hospital, Aachen, Germany.

Objective: Misoprostol is safe and effective for labor induction in viable pregnancies. Little is known about the prevalence of off-label use of misoprostol, and the reasons for using or not using misoprostol for labor induction. As such, a national survey was conducted in Germany to assess reliable data about the use of misoprostol in clinical practice.

Study Design: A prospective study was performed in 2013 using a standardized survey questionnaire. All registered departments of obstetrics and gynecology in Germany were targeted.

Results: Out of 783 questionnaires, 542 (69%) were returned. Three hundred and fifty-five (66%) respondents reported that they use misoprostol for labor induction in viable term pregnancies, and 183 (34%) respondents reported that they never use misoprostol for this indication. The most common reasons given for using misoprostol in labor induction were: effectiveness (40%), good patient acceptance (35%), established/well proven in clinical practice (35%) and cost-effectiveness (32%). The most common reasons given for not using misoprostol were lack of licence (off-label use, 69%) and uncertainty of the legal situation (27%).

Conclusion: Although misoprostol is not licensed in Germany for obstetric indications, the vast majority of respondents (66%) reported that they use misoprostol for labor induction. The main reasons for not using misoprostol for labor induction in Germany are legal concerns rather than lack of scientific evidence. Cost-effective medications with evidence-based effectiveness and safety should be supported by a clear statement from national medical societies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2014.11.026DOI Listing
April 2015

Fulminant puerperal sepsis due to anaplastic large-cell lymphoma (ALCL) with therapy-refractory cerebral edema.

Arch Gynecol Obstet 2014 Jul 23;290(1):191-3. Epub 2014 Feb 23.

Department of Obstetrics and Gynecology, University Hospital Aachen, Pauwelsstr. 30, 52074, Aachen, Germany,

Introduction: Lymphoma is among the five most frequent malignancies during pregnancy while anaplastic large-cell lymphoma (ALCL) is rare, accounting only for 2-3 % of all adult-onset non-Hodgkin lymphomas.

Case Report: A 23-year-old gravida 1, para 1 presented with puerperal mastitis and septicemia following secondary cesarean section. Mastitis had been present for a week prior to delivery. A CT scan for further diagnostics revealed numerous prominent lymph nodes. Cerebrospinal fluid testing, bone marrow and lymph node biopsy confirmed diagnosis of ALCL. Systemic and intrathecal chemotherapy was initiated, stabilizing the patient's clinical situation. 30 days postpartum (pp.), a cerebral edema was diagnosed responsible for cerebro-venous hypoperfusion. Immediate ventricle drainage and further therapeutic measures revealed no improvement. The patient died 33 days pp.

Conclusion: Puerperal septicemia seemingly caused by mastitis still needs rapid further evaluation if the patient's clinical presentation quickly declines despite antibiotic therapy. Immediate initiation of chemotherapy after confirmation of ALCL is required to increase the therapeutic benefit due to the poor prognosis of ALCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-014-3171-2DOI Listing
July 2014

Oxidatively modified LDL particles in the human placenta in early and late onset intrauterine growth restriction.

Placenta 2013 Dec;34(12):1142-9

Introduction: Reduced serum LDL concentrations have been observed in pregnancies complicated by intrauterine growth restriction (IUGR) as compared to healthy pregnant women. Since increased oxidative stress has been suggested to play a major role in IUGR we now hypothesized that the lower LDL concentrations are accompanied by an accumulation of oxidized LDLs in the placenta.

Methods: Fifteen placentas of near term and preterm born IUGR, and a gestational age matched control group (CTRL n = 15) were analyzed. Placental minimal modified LDL and fully oxidized LDL particles were measured by ELISA, and by immunohistochemistry, and were related to maternal and fetal serum lipid profiles.

Results: We found fully oxidized LDL but not minimal modified LDL being increased in the preterm subgroup of IUGR (n = 10) as compared to preterm CTRL (n = 10; p < 0.05). An increased staining intensity of trophoblasts in preterm IUGR subjects as compared to preterm CTRL has been confirmed by immunohistochemistry (p < 0.05). No difference could be found between the term groups (n = 5 each). Correlation analysis revealed an inverse relationship of maternal LDL (ρ = −0.49, p = 0.03) and fetal HDL cholesterol (ρ = −0.46, p = 0.04) with placental fully oxidized LDL particle concentration within preterms.

Discussion: IUGR is a heterogeneous entity. Different pathomechanisms seem to underlie the disease in preterm and term subjects with oxidation of LDL within the placenta possibly taking place in preterm IUGRs.

Conclusions: We conclude that the reduced maternal LDL cholesterol concentration in IUGR pregnancies is attributed to increased accumulation of oxidized LDL particles within the placenta at least in early onset IUGR
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.placenta.2013.10.006DOI Listing
December 2013

Mass spectrometric profiling of cord blood serum proteomes to distinguish infants with intrauterine growth restriction from those who are small for gestational age and from control individuals.

Transl Res 2014 Jul 10;164(1):57-69. Epub 2013 Dec 10.

Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Rostock, Germany. Electronic address:

Intrauterine growth restriction (IUGR) is a multifactorial condition in that the fetus does not reach its genetically given growth potential. Besides its contribution to perinatal mortality, it is a risk factor for cardiovascular and metabolic diseases later in life. The diagnosis is based on antenatal sonography, which allows differentiating between IUGR and fetuses that are small by constitution (small for gestational age [SGA]). Yet, neither a clinical nor a biochemical tool is available to confirm reliably the diagnosis of IUGR postnatally. Recently, we identified umbilical cord blood proteins of the apolipoprotein family by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with differential signal intensities between the IUGR group and a control group. We hypothesized that identified molecules have the potential to generate a proteome profile specific for IUGR. A total of 114 serum samples (42 from the IUGR group, 12 from the SGA group, and 60 from the control group) of the umbilical vein (99 samples) and umbilical artery (15 samples) were analyzed. Sample quality was estimated by determining the abundance of hemoglobin (hemolysis) and CXC-motif chemokines CXCL4 and CXCL7 (platelet activation). Samples passing the quality criteria were forwarded to multiplex apolipoprotein profiling. Assay performance was tested with the sample sets, resulting in a sensitivity of 0.91 and a specificity of 0.85 in the test set with venous blood samples. Arterial cord blood samples followed the trend (sensitivity, 0.67; specificity, 0.85). SGA samples grouped together with the control samples. We conclude that the proteome profiling signature is confirmatory to clinical surveillance with the potential to identify neonates with IUGR postnatally in low-birth weight babies born at uncertain gestational age when antenatal sonography data have not been recorded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trsl.2013.12.003DOI Listing
July 2014

Cholesterol acceptor capacity is preserved by different mechanisms in preterm and term fetuses.

Biochim Biophys Acta 2014 Feb;1841(2):251-8

Fetal serum cholesterol and lipoprotein concentrations differ between preterm and term born neonates. An imbalance of the flow of cholesterol from the sites of synthesis or efflux from cells of peripheral organs to the liver, the reverse cholesterol transport (RCT), is linked to atherosclerosis and cardiovascular disease (CVD). Preterm delivery is a risk factor for the development of CVD. Thus, we hypothesized that RCT is affected by a diminished cholesterol acceptor capacity in preterm as compared to term fetuses. Cholesterol efflux assays were performed in RAW264.7, HepG2, and HUVEC cell lines. In the presence and absence of ABC transporter overexpression by TO-901317, umbilical cord sera of preterm and term born neonates (n = 28 in both groups) were added. Lipid components including high density lipoprotein (HDL), low density lipoprotein (LDL), apolipoprotein A1, and apolipoprotein E were measured and related to fractional cholesterol efflux values. We found overall, fractional cholesterol efflux to remain constant between the study groups, and over gestational ages at delivery, respectively. However, correlation analysis revealed cholesterol efflux values to be predominantly related to HDL concentration at term, while in preterm neonates, cholesterol efflux was mainly associated with LDL In conclusion cholesterol acceptor capacity during fetal development is kept in a steady state with different mechanisms and lipid fractions involved at distinct stages during the second half of fetal development. However, RCT mechanisms in preterm neonates seem not to be involved in the development of CVD later in life suggesting rather changes in the lipoprotein pattern causative.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbalip.2013.11.008DOI Listing
February 2014

PP031. The fetal cholesterol acceptor potential in cord sera of intrauterine growth restricted (IUGR) neonates.

Pregnancy Hypertens 2013 Apr 6;3(2):78. Epub 2013 Jun 6.

Introduction: The fetal umbilical cord blood cholesterol concentration is lower in IUGR neonates as compared to gestational age matched controls (CTRL). One possible explanation is an alteration of cholesterol acceptor concentration or functionality and a disturbed interaction with reverse cholesterol transport (RCT) mechanisms at the placentofetal interface.

Objective: To study receptor specific mechanisms of RCT in response to fetal sera of IUGR and CTRL neonates.

Methodes: Different cell lines were used to determine the fractional efflux of (3)H-cholesterol in response to whole fetal serum (IUGR n=25; CTRL n=25) in the absence or presence of ABCA1 overexpression. Efflux values were correlated to serum concentrations of possible cholesterol acceptors like HDL, apoA1, and apoE.

Results: The main finding was a significant over all reduction of fractional cholesterol efflux in response to IUGR serum as compared to CTRL (p<0.001). The differences were abolished after overexpression of ABCA1. Cholesterol efflux over all was highly correlated to HDL and ApoE concentration (n˜=0.777 and n˜=0.60).

Conclusion: The reduced cholesterol efflux acceptor capacity appears to diminish cholesterol availability and transplacental cholesterol transport to IUGR fetuses. Moreover, disturbances of RCT are involved in the pathomechanisms of atherosclerosis. Our results represent a link between the known association of being born small for gestational age and risk of developing CVD later in life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2013.04.058DOI Listing
April 2013

PP032. Apolipoprotein profiling in umbilical cord blood of intrauterine growth restricted (IUGR) neonates.

Pregnancy Hypertens 2013 Apr 6;3(2):78. Epub 2013 Jun 6.

Introduction: Fetal umbilical cord HDL concentration is lower in IUGR neonates as compared to gestational age matched controls (CTRL). The causes by now are unknown. A full apolipoprotein analysis of cord blood might help in understanding the changes in lipid metabolism seen in IUGR.

Objective: To characterize cord blood apolipoprotein profile of IUGR neonates.

Methods: Serum of venous umbilical cord blood (15 IUGR vs. 15 CTRL) was analyzed by Multiple Reaction Monitoring (MRM). 15 different known apolipoproteins were profiled. HDL and LDL were measured by colorimetric methods in fetal cord blood and their corresponding mothers.

Results: Fetal HDL (p<0.0001), ApoC1 (p<0.0001), and ApoE (p=0.0001) levels were lower in IUGR as compared to CTRL. Fetal HDL levels were positive correlated to ApoE, ApoC1, and ApoA2 (r=0.79, r=0.74, r=0.56). Fetal LDL levels were positive correlated to ApoB, ApoE, ApoA2, and ApoC3 (r=0.74, r=0.67, r=0.57, r=0.55). Maternal LDL concentrations correlated positive to fetal ApoC1, ApoC2, and LCAT-concentration (r=0.54, r=0.52, r=0.52).

Discussion: The results underlines the relevance of ApoE in fetal development. Moreover, we speculate that maternal lipid profile has an impact on fetal lipid metabolisms as evidenced by the association of maternal LDL levels and fetal ApoC1, ApoC2, and LCAT concentrations. This observation requires further confirmation and is worth to be analyzed since it provides a mechanistic link for therapeutic options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2013.04.059DOI Listing
April 2013

PP033. Oxidized LDL particles in the placenta of intrauterine growth restriction (IUGR) subgroups.

Pregnancy Hypertens 2013 Apr 6;3(2):78-9. Epub 2013 Jun 6.

Introduction: Maternal serum LDL concentrations are lower in IUGR pregnancies as compared to controls (CTRL). We now hypothesized that an increased oxidative stress results in the formation of oxidized LDL (oxLDL) particles which than accumulates within the placenta. This is particularly hypothesized for the severe early onset subgroup of IUGR with preeclampsia (PE).

Methods: OxLDL (minimal modified and fully oxidized LDL) levels in placental biopsies from term IUGR (>37 weeks, t-IUGR, n=5), preterm IUGR (<34 weeks, p-IUGR, n=5), and preterm IUGR with PE (PE-IUGR, n=5) were compared to a CTRL group consisted of gestational age matched preterm (p-CTRL, n=10) and term (t-CTRL, n=5) placentas by ELISA and immunohistochemistry (IHC).

Results: Fully oxidized LDL but not minimally oxidized LDL concentrations were higher in p-IUGR and tend to be increased in PE-IUGR when compared to p-CTRL (p=0.040 and p=0.075). There was virtually no difference of fully oxidized LDL levels between p-CTRL, t-CTRL, and t-IUGR. We confirmed a higher oxLDL accumulation in trophoblasts of p-IUGR and PE-IUGR as compared to both CTRL groups by IHC though this was not statistically significant.

Conclusion: Conformational changes of LDL during the process of oxidation might lead to an accumulation of oxLDL particles in placental tissue of IUGR. The pathogenesis of early onset IUGR might differ from those of late onset IUGR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2013.04.060DOI Listing
April 2013

PP019. A new player in preeclampsia: The NF-E2-related factor 2 (NRF2).

Pregnancy Hypertens 2013 Apr 6;3(2):74. Epub 2013 Jun 6.

Introduction: Preeclampsia PE is characterized by diminished antioxidant capacity. These enzymes are mainly regulated via the transcription factor Nrf2.

Objectives: PE is associated with an increase in Nrf2 activity. Nrf2 involves also in the vascular homeostasis during PE. Respective hemodisturbances have been associated with impaired invasion of the extravillous trophoblast EVT in early onset IUGR associated with PE. To test this link, we studied in vitro the interaction between Nrf2 and VEGF, then their expression was determined in third trimester placental beds in cases of severe early onset IUGR/PE.

Methods: BeWo cells were used in the in vitro study.Western blot; ELISA and Dual Luciferase assay were applied. Full-thickness uterine tissues from 6 healthy and 6 women with severe early onset IUGR/PE were used to study the expression of VEGF, Nrf2 and 4-HNE in the EVT.

Results: Nrf2-activation and its downstream target protein HO-1 augmented CO production, which in turn up-regulated the expression of VEGF. EVT in cases with IUGR/PE showed increased expression of Nrf2 and decreased VEGF intensity.

Conclusion: In early onset IUGR/PE the EVT experience oxidative stress and try to counteract this by increased expression of Nrf2. However, since these cells fail to up-regulate VEGF, Nrf2-activation does not occur, leading to further trophoblast damage. At the same time, in vitro data show a protective role of the Nrf2/HO-1 pathway, which may have a therapeutic potential in PE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2013.04.047DOI Listing
April 2013

PP020. Evidence of a preventive role of Nrf2 in preeclampsia.

Pregnancy Hypertens 2013 Apr 6;3(2):74. Epub 2013 Jun 6.

Introduction: Smoking during pregnancy is associated with lower preeclampsia risk. This has been mainly explained through the effect of carbon monoxide CO.

Objectives: Recent studies showed that the activation of heme oxygenase-1 HO-1 and consequently its metabolite CO in cultured cells mediated an inhibition of sFlt-1 and sEng release, and an up-regulation of the endogenous VEGF. The transcriptional regulation of the HO-1 gene is majorly regulated through the transcription factor Nrf2. The aim of this study was to investigate in vitro the effect of HO-1-activation via Nrf2 on the pro- and anti-angiogenic factors.

Methods: BeWo cells and HUVECs endothelial cells were used to study the angiogenic effect of Nrf2-activation. ELISA, scratch and tube formation assay were mainly applied.

Results: The activation of HO-1 via Nrf2 lead to an increase in the protein levels of VEGF (control 64.75pg/ml±4.3; Sulforaphane-treated cells 128.2pg/ml±6.5 p<0.005) and decrease in the augmented sFlt-1 in the supernatant of the treated cells (control 186.3pg/ml±28.7; H2O2-treatment 2026pg/ml±64, co-treatment with H2O2 and Sulforaphane 1200pg/ml±19.7 p<0.01). Up-regulation of HO-1/CO enhanced tube formation and migration of the endothelial cells.

Conclusion: The activation of HO-1/CO via Nrf2 inducer such as sulforaphane inhibited in vitro the release of sFlt-1, thus the activation of Nrf2 during the first trimester may improve the balance of the pro- and anti-angiogenic factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2013.04.048DOI Listing
April 2013

[Determination of maternal and foetal serum lipid profile and placental oxidised low density lipoprotein accumulation in preeclampsia and normotensive pregnancies].

Z Geburtshilfe Neonatol 2012 Oct 29;216(5):220-5. Epub 2012 Oct 29.

Frauenklinik für Gynäkologie und Geburtsmedizin des Universitätsklinikums der RWTH Aachen.

Background: Oxidised low density lipoproteins (oxLDL) are key players in the development of atherosclerotic cardiovascular diseases. Since there are similarities between the pathogenesis of preeclampsia and atherosclerosis we hypothesised an increased accumulation of oxLDL at the materno-foetal and foeto-foetal interface within the placental tissue of preeclamptic women compared to women with normotensive pregnancies (controls). Moreover, we analysed maternal and foetal serum lipid parameters.

Patients And Methods: oxLDL was determined by immunohistochemistry in placental paraffin sections of 14 women suffering from preeclampsia (30th-39th week of gestation) and compared to 28 preterm and term deliveries (25th-40th week of gestation). 10 high power fields were chosen randomly by the newCAST software and oxLDL expression was analysed via standardised methods by 2 independent and blinded investigators. Maternal and foetal triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol were measured. Statistical examination was carried out by the Mann-Whitney test.

Results: oxLDL was found in villous trophoblast and placental endothelium. No significant differences were observed in expression intensity between preeclampsia and controls. Maternal and foetal triglyceride levels were significantly increased in preeclampsia compared to controls (pre-eclampsia mothers: 293 [SD 87.4] mg/dL, controls: 214 [SD 89.4] mg/dL, p=0.0097; preeclampsia foetuses: 26 [SD 16.6] mg/dL, controls: 18 [SD 10.4] mg/dL, p=0.0463). No significant differences in other lipid concentrations were found.

Conclusions: We could not confirm our initial hypothesis of an increased oxLDL accumulation in placental tissue of preeclampsia. However, preeclampsia is a condition of dyslipidaemia affecting both maternal and foetal serum with implications for development and programming of cardiovascular diseases in later life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0032-1323793DOI Listing
October 2012

Angiogenic factors and acute-phase proteins in serum samples of preeclampsia and HELLP patients: a matched-pair analysis.

J Matern Fetal Neonatal Med 2013 Feb 19;26(3):263-9. Epub 2012 Oct 19.

University of Rostock, Department of Obstetrics and Gynecology, Rostock, Germany.

Objectives: To investigate the serum level distribution of angiogenic markers (PlGF, endoglin, sFlt-1) and acute-phase proteins (SAA, CRP) in patients with HELLP syndrome or preeclampsia (PE) including matched controls.

Methods: The matching procedure revealed 46 controls for 23 HELLP cases, and 81 controls for 42 preeclamptic patients. Maternal serum concentrations were determined by immunoassays.

Results: SAA and CRP levels were significantly higher in HELLP patients compared with controls. This finding was not observed in preeclamptic subgroup. Pro-angiogenic PlGF is significantly lower in PE and HELLP syndrome. Anti-angiogenic endoglin is significantly higher in PE and HELLP syndrome. The sFlt-1 analysis supports the anti-angiogenic shift in HELLP and preeclamptic patients, but with smaller differences between subgroups. The SAA/PlGF ratio showed the highest ROC value of all tested parameters in discrimination between HELLP and HELLP controls.

Conclusions: These findings support the concept that patients with HELLP syndrome have both an anti-angiogenic state and a pronounced inflammatory response, while patients with PE are characterized only by an anti-angiogenic shift.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/14767058.2012.733747DOI Listing
February 2013

PP119. The role of the nuclear factor erythroid 2-related factor 2 (Nrf2) in preeclampsia.

Pregnancy Hypertens 2012 Jul 13;2(3):303-4. Epub 2012 Jun 13.

Department of Anatomy and Cell Biology, RWTH Aachen University, Germany.

Introduction: Preeclampsia is a multi-organ syndrome characterized by maternal endothelial damage, is an independent long-term risk factor for hypertension and cardiovascular disease.

Objectives: In animal models the administration of the Vascular Endothelial Growth Factor (VEGF) could reverse the hypertensive signs accompanying this disease. In addition VEGF is implicated in placental oxidative stress during preeclampsia. One of the major cellular defence mechanisms against oxidative stress is the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2). Therefore, the activation of Nrf2 up regulates the HO-1/CO system. The principal aim of this work is to investigate whether the activation of Nrf2 raises VEGF levels by up regulation of CO release.

Methods: This study took place in vitro, the choriocarcinoma cell line BeWo cells and the primary human umbilical vein endothelial cells (HUVECs) were used to study the relationship between VEGF and an Nrf2 inducer Sulforaphane, a naturally occurring compound derived from broccoli. ELISA, Western blot assay and the Dual Luciferase Assay were both mainly applied for protein and VEGF activity analysis.

Results: It was found that activation of HO-1 expression via Nrf2/ARE pathway augmented the production of CO, which in turn up-regulated the gene expression of VEGF, and down regulated the production of the antiangiogenic protein, the VEGF antagonist sFlt-1.

Conclusion: Nrf2 driven HO-1 expression elevates the levels of VEGF via CO production. In particular, activating of Nrf2 via sulforaphane, may have therapeutic potential in preeclampsia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2012.04.230DOI Listing
July 2012

PP014. Estimating fully and minimal oxidized low density lipoprotein accumulation in placental tissue in intrauterine growth restriction and healthy controls.

Pregnancy Hypertens 2012 Jul 13;2(3):248. Epub 2012 Jun 13.

Institute of Cell Biology, Histology, and Embryology, Medical Faculty, Graz, Austria.

Introduction: We recently demonstrated that maternal serum LDL- and fetal serum HDL-cholesterol concentration is significantly reduced in intrauterine growth restriction (IUGR) [1].

Objectives: We now hypothesized that increased oxidative stress in IUGR placenta leads to an accumulation of oxidized LDL (oxLDL) particles which then become trapped within the placenta subsequently leading to reduced availability of cholesterol for mother and fetus.

Methods: Fully oxidized LDL (oxLDL) was determined via immunohistochemistry in placental paraffin sections of 18 women suffering from IUGR and 18 gestational age matched controls. Ten 'High Power Fields' were chosen randomly by the newCAST software and oxLDL expression was estimated via standardized methods by two independent and blinded observers. Minimal oxidatively modified LDL (MM-LDL) and non-modified Apolipoprotein B (ApoB) concentration was measured in full placental tissue lysates by ELISA. Values were correlated with maternal and fetal total cholesterol, LDL-, and HDL-cholesterol concentrations. Statistical examinations were carried out by Student's t-test and calculation of Pearson's correlation coefficient.

Results: oxLDL was found predominantly to be in villous trophoblast and placental endothelium. OxLDL intensity tended to be increased in IUGR (Table 1). We found MM-LDL concentrations in whole placental tissue lysates to be highly correlated to placental ApoB concentration (r=0.93). Both parameters were non-significantly decreased in placenta of IUGR compared to controls (Table 1). Maternal serum LDL-C, and fetal serum LDL-C, TC, and HDL-C concentrations were significantly decreased in IUGR compared to controls (Table 2). OxLDL staining intensity was mildly negatively correlated to maternal LDL-C (r=-0.315) and much less to fetal HDL-C concentrations (r=-0.212). Placental ApoB and MM-LDL concentration were moderately positively correlated with fetal HDL-C concentrations (r=0.492 and r=0.447).

Conclusion: Conformational changes of the ApoB lipoprotein during the process of oxidation might lead to an accumulation of oxLDL particles in placental tissue of IUGR and reduced fetal cholesterol bioavailability as evidenced by a decrease in fetal serum cholesterol levels. However, our analysis lacks in sufficient power and further studies are underway focussing on that subject.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2012.04.125DOI Listing
July 2012

PP013. Oxidized low density lipoprotein accumulation and the expression of the lectin-like oxLDL receptor (LOX-1) in placental tissue in preeclampsia and healthy controls.

Pregnancy Hypertens 2012 Jul 13;2(3):247-8. Epub 2012 Jun 13.

Department of Obstetrics and Gynecology, University Hospital of the RWTH Aachen, Aachen, Germany.

Introduction: Oxidized Low Density Lipoproteins (oxLDL) and its receptor the lectin-like oxLDL receptor 1 (LOX-1) are key players in the development of atherosclerotic cardiovascular diseases.

Objectives: Since preeclampsia is known to share similarities to the pathogenesis of atherosclerosis we hypothesized an increased accumulation of oxLDL and an increased expression of LOX-1 at the materno-fetal and feto-fetal interface within the placental tissue in preeclampsia in comparison to a control group. Second, we analyzed maternal and fetal serum lipid parameters including fetal oxLDL concentration.

Methods: OxLDL and LOX-1 intensity was determined via immunohistochemistry in placental paraffin sections of 11 women suffering from preeclampsia and compared to 11 gestational age matched preterm deliveries (29th to 36th week of gestation). Ten 'High Power Fields' were chosen randomly by the newCAST software and expression was analyzed via standardized methods by two independent and blinded observers. Maternal and fetal triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol were measured by enzymatic colorimetric methods. Fetal oxLDL serum concentration was estimated by ELISA. Statistical examination was carried out by Student's t-test. Skewed variables were log-transformed.

Results: oxLDL and LOX-1 was predominantly found to be in villous trophoblast and placental endothelium. No significant differences could be observed in oxLDL expression intensities between preeclampsia and controls. LOX-1 expression tended to be increased in placental trophoblast and endothelium without being statistical significant (Table 1). Fetal triglyceride levels were significantly elevated in preeclampsia compared to controls while maternal triglyceride levels tend to be increased. No other significant differences in lipid concentrations could be observed (Table 2).

Conclusion: We could not confirm our initial hypothesis of an accelerated oxLDL accumulation in placental tissue of preeclampsia. Though not statistically significant, placental endothelium seems to be activated in preeclampsia since LOX-1 expression is increased. Moreover, preeclampsia is a condition of dyslipidemia affecting both, maternal and fetal serum with implications for development of cardiovascular diseases in later life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2012.04.124DOI Listing
July 2012

OS079. Fetal deglycosylated apolipoprotein C-III (Apo C-III0) concentration is altered in intrauterine growth restriction.

Pregnancy Hypertens 2012 Jul 13;2(3):220-1. Epub 2012 Jun 13.

Proteome Center, University of Rostock, Rostock, Germany.

Introduction: We recently demonstrated that serum lipid levels are altered in growth restricted fetuses (IUGR) [1].

Objectives: We now aimed to analyse the proteome profile of umbilical cord blood in order to gain a greater understanding about metabolic changes in IUGR fetuses.

Methods: umbilical cord blood serum samples of IUGR (n=15) and of gestational age matched controls (CN; n=15) were subjected to fractionation by affinity chromatography using a bead system with hydrophobic interaction capabilities. So prepared protein mixtures were forwarded to MALDI-TOF mass spectrometric profiling. Assignment of ion signals in the mass spectra to specific proteins was substantiated by SDS-PAGE in conjunction with peptide mass fingerprint analysis. Concentrations of proteins of interest were additionally measured by ELISA. Statistical estimations were performed by Student's t-test and calculation of Spearman's correlation coefficient.

Results: MALDI mass spectra showed on average more than 60 protein ion signals between m/z 4000 and 25,000. The six best differentiating ion signals were found at m/z 8205, m/z 8766, m/z 13,945, m/z 15,129, m/z 15,308, and m/z 16,001. One of the constituent of this proteome signature is the deglycosylated form of apolipoprotein C-III, apo C-III0 (8766 m/z) that is known to prevent triglycerides from catabolism. While total Apo CIII concentration tended to be decreased (IUGR 22.54μg/mL SD 10.25. CN 29.9μg/mL SD 15.46. p=0.1355) calculated Apo C-III0 concentration levels has been found to be more abundant in the IUGR cord blood serum samples (IUGR 1.99μg/mL SD 0.85. CN 1.15μg/mL SD 0.55. p<0.0001). Moreover, fetal triglycerid levels were significantly increased in IUGR (IUGR 16.7mg/dL SD 7.58. CN 56.5mg/dL SD 49.92. p-value after log transformation =0.0008)and apo C-III0 was highly correlated to fetal triglyceride levels (rho=0.694).

Conclusion: Using mass spectrometric approaches we successfully developed an IUGR specific proteome signature derived from human umbilical cord blood samples. Most interesting the deglycosylated form of the apolipoprotein C-III (apoC-III0) was found to be significantly increased in IUGR and thus might lead to reduced triglyceride catabolism. This observation is in agreement with the known observation of triglyceride levels being increased in IUGR fetuses. Our results indicate that subtle alterations in protein glycosylation need to be considered for improving our understanding of the pathomechanisms in IUGR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.preghy.2012.04.080DOI Listing
July 2012

A proteome signature for intrauterine growth restriction derived from multifactorial analysis of mass spectrometry-based cord blood serum profiling.

Electrophoresis 2012 Jul;33(12):1881-93

Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Rostock, Germany.

Intrauterine growth restriction (IUGR) is defined as a condition in which the fetus does not reach its genetically given growth potential, resulting in low birth weight. IUGR is an important cause of perinatal morbidity and mortality, thus contributing substantially to medically indicated preterm birth in order to prevent fetal death. We subjected umbilical cord blood serum samples either belonging to the IUGR group (n = 15) or to the control group (n = 15) to fractionation by affinity chromatography using a bead system with hydrophobic interaction capabilities. So prepared protein mixtures were analyzed by MALDI-TOF mass spectrometric profiling. The six best differentiating ion signals at m/z 8205, m/z 8766, m/z 13 945, m/z 15 129, m/z 15 308, and m/z 16 001 were collectively assigned as IUGR proteome signature. Separation confidence of our IUGR proteome signature reached a sensitivity of 0.87 and a specificity of 0.93. Assignment of ion signals in the mass spectra to specific proteins was substantiated by SDS-PAGE in conjunction with peptide mass fingerprint analysis of cord blood serum proteins. One constituent of this proteome signature, apolipoprotein C-III(0) , a derivative lacking glycosylation, has been found more abundant in the IUGR cord blood serum samples, irrespective of gestational age. Hence, we suggest apolipoprotein C-III(0) as potential key-marker of the here proposed IUGR proteome signature, as it is a very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) member and as such involved in triglyceride metabolism that itself is discussed as being of importance in IUGR pathogenesis. Our results indicate that subtle alterations in protein glycosylation need to be considered for improving our understanding of the pathomechanisms in IUGR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/elps.201200001DOI Listing
July 2012

Anti-oxidized low-density lipoprotein (oxLDL) antibody levels are not related to increasing circulating oxLDL concentrations during the course of pregnancy.

Am J Reprod Immunol 2012 Oct 17;68(4):345-52. Epub 2012 May 17.

Department of Obstetrics and Gynecology, University Hospital of the RWTH Aachen, Aachen, Germany.

Problem: To address the question of whether the high levels of oxidative modified low-density lipoproteins (oxLDL) in pregnancy are opposed by an appropriate humoral autoimmune response providing anti-oxLDL autoantibodies in maternal serum of healthy women throughout gestation.

Method Of Study: Blood was taken from 33 patients at four different time points from early to late gestation and post-partum. OxLDL and anti-oxLDL concentrations were measured by enzyme-linked immunosorbent assays. ANOVA was used for statistical evaluations followed by post hoc test with Bonferoni adjustment.

Results: Oxidized Low Density Lipoprotein concentrations increased while anti-oxLDL levels decreased significantly from early to late gestation. OxLDL was strongly positively correlated with LDL concentration and mildly negatively associated with anti-oxLDL levels. Estimating the status of oxidation by calculating oxLDL/LDL ratio revealed decreasing values with ongoing pregnancy. Multivariate analysis showed that anti-oxLDL levels were dependent on gestational age but neither on oxLDL levels nor on the oxLDL/LDL ratio.

Conclusions: The results indicate that normal pregnancy is a well-balanced state of oxidative and anti-oxidative processes. However, we could not confirm a dependence of anti-oxLDL autoantibodies on oxLDL concentration. Whether or not the humoral immune system is involved in oxidative defence remains to be elucidated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0897.2012.01157.xDOI Listing
October 2012

A mass spectrometric multicenter study supports classification of preeclampsia as heterogeneous disorder.

Hypertens Pregnancy 2012 ;31(2):278-91

Department of Obstetrics and Gynecology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Objective: The diagnostic value of affinity-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis to distinguish preeclampsia (PE) from matched controls was tested in a multicenter setting.

Methods: Serum samples of preeclamptic (n = 60) and healthy pregnant women (n = 66) from four centers were prospectively analyzed with predefined rule sets.

Results: Overall sample classification reached sensitivity of 0.88 and specificity of 0.73. Separate calculations for early-onset PEs only (before 34 weeks of gestation) revealed sensitivity of 0.88 and specificity of 0.89.

Conclusion: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry serum-profiling with center-wise standardization offers a fast and robust method to classify PE and contributes to the theory of PE being a heterogeneous disorder that ought to be subclassified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10641955.2011.640375DOI Listing
September 2012

Maternal and fetal cord blood lipids in intrauterine growth restriction.

J Perinat Med 2012 Jan 6;40(3):287-96. Epub 2012 Jan 6.

Department of Obstetrics and Gynecology of the University Hospital of the RWTH Aachen, Germany.

Aim: Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses.

Methods: Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery.

Results: Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P<0.001, TC: P<0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P<0.001).

Conclusion: Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpm.2011.135DOI Listing
January 2012
-->