N-terminal pro-C-type natriuretic peptide, but not C-type natriuretic peptide, is greatly elevated in the fetal circulation

2004 ◽  
Vol 106 (5) ◽  
pp. 535-540 ◽  
Author(s):  
Timothy C. R. PRICKETT ◽  
Risto J. KAAJA ◽  
M. Gary NICHOLLS ◽  
Eric A. ESPINER ◽  
A. Mark RICHARDS ◽  
...  
Keyword(s):  
Cord Blood ◽  
Natriuretic Peptide ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Plasma Concentrations ◽  
Maternal Plasma ◽  
Fetal Tissues ◽  
Cord Plasma ◽  
Significant Difference ◽  
Gestational Group

We have identified recently a new peptide, NT-proCNP(1–50) (N-terminal pro-C-type natriuretic peptide), in the circulation of humans and sheep. A previous report of an elevated fetal–maternal gradient in immunoreactive CNP raised the possibility that processing and metabolism of proCNP may differ in maternal and fetal tissues. We therefore collected matching peripheral maternal and umbilical cord plasma samples at delivery from women with normotensive and pre-eclamptic pregnancies to investigate the presence and concentrations of CNP and NT-proCNP using HPLC and RIA. Plasma concentrations of NT-proCNP in normotensive umbilical cord plasma were 10-fold higher than maternal venous levels (246±17 compared with 24.3±1.8 pmol/l; P<0.001) and much higher than corresponding levels of CNP (3.6±0.4 compared with 1.8±0.3 pmol/l in the fetal and maternal plasma respectively; P<0.001). Although there was no significant difference between normotensive and pre-eclamptic plasma CNP concentrations in either maternal or umbilical cord blood, NT-proCNP showed a significant statistical interaction (F=5.8, P=0.025) between the source (maternal or fetal) and gestational group (normotensive or pre-eclamptic). Maternal NT-proCNP levels were raised in the pre-eclampsia group, whereas the converse was observed in umbilical cord blood. In conclusion, the greatly elevated ratio of NT-proCNP/CNP in fetal compared with maternal plasma suggests that synthesis, as well as clearance, of CNP (but not NT-proCNP clearance) are markedly increased in fetal tissues.

Secretion of atrial natriuretic peptide and digoxin-like immunoreactive substance during pregnancy.

1988 ◽  
Vol 34 (5) ◽  
pp. 977-980 ◽  
Author(s):  
P Shrivastav ◽  
D S Gill ◽  
V D'Souza ◽  
P M O'Brien ◽  
P Dandona
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Umbilical Cord ◽  
Maternal Plasma ◽  
Cord Plasma ◽  
Significant Difference ◽  
Atrial Natriuretic

Abstract We investigated the secretion of atrial natriuretic peptide (ANP) and digoxin-like immunoreactive substance (DLIS) during pregnancy, labor, and the puerperium, as measured in maternal and umbilical cord plasma. There were no significant changes in maternal concentrations of ANP during all three periods, and the concentrations were similar to those found in nonpregnant controls and in umbilical cord plasma. Maternal concentrations of DLIS increased significantly in the second half of pregnancy, peaked during labor, then decreased abruptly within 24 h of expulsion of the infant and placenta to values approaching the nonpregnant range. DLIS concentrations in umbilical cord plasma, however, were significantly higher than in maternal plasma during labor. The abrupt fall in DLIS in maternal plasma and the absence of a significant difference in DLIS concentrations between arterial and venous cord plasma suggest that, during pregnancy, the fetus, not the placenta, is the source of DLIS in maternal plasma.

THE CONCENTRATIONS OF ANDROGENS, OESTROGENS, PROGESTERONE AND LUTEINIZING HORMONE IN THE SERUM OF FOETAL CALVES THROUGHOUT THE COURSE OF GESTATION

1974 ◽  
Vol 60 (1) ◽  
pp. 107-115 ◽  
Author(s):  
J. R. G. CHALLIS ◽  
C. K. KIM ◽  
F. NAFTOLIN ◽  
H. L. JUDD ◽  
S. S. C. YEN ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Maternal Plasma ◽  
Male And Female ◽  
Hormone Levels

SUMMARY The concentrations of luteinizing hormone (LH), progesterone, testosterone, androstenedione, oestrone and oestradiol in mixed umbilical cord blood taken from foetal calves during months 3 to 9 of gestation have been measured by radioimmunoassay. The levels of progesterone were low (compared with those in maternal plasma) and constant during pregnancy. There were large variations in the concentrations of androstenedione, oestrone, oestradiol and LH, with lower values found during months 7 to 8 of gestation. Significant differences (P < 0·05–< 0·001) in hormone levels between male and female foetuses were found for testosterone, LH, and the oestrogens during months 3 to 7, 3 and 4, and 7 and 8, respectively. No significant differences (P > 0·05) between sexes were found at any time between the concentrations of progesterone and androstenedione.

Reference Values for N-Terminal Pro-B-Type Natriuretic Peptide in Umbilical Cord Blood

2004 ◽  
Vol 50 (12) ◽  
pp. 2465-2465 ◽  
Author(s):  
Jaap Bakker ◽  
Inge Gies ◽  
Barbara Slavenburg ◽  
Otto Bekers ◽  
Tammo Delhaas ◽  
...  
Keyword(s):  
Cord Blood ◽  
Natriuretic Peptide ◽  
Umbilical Cord ◽  
Reference Values ◽  
Umbilical Cord Blood

Culture of CD34+ Umbilical Cord Blood Progenitors with Notch Ligand Results in Enhanced and More Rapid Human Engraftment in a Preclinical NOD/SCID Mouse Model.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 190-190 ◽  
Author(s):  
Colleen Delaney ◽  
Irwin D. Bernstein
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Culture Period ◽  
Unrelated Donor ◽  
Culture Vessel ◽  
Notch Ligand ◽  
Significant Difference

Prior clinical studies have indicated that total nucleated and CD34+ cell dose is a critical determinant of hematopoietic reconstitution and survival after unrelated donor umbilical cord blood (UCB) transplantation. Efforts to overcome the problem of small cell numbers in UCB grafts by ex vivo expansion, primarily by culture with cytokines, have not met with success. We have previously shown that culture of CD34+CD38− UCB progenitors with the Notch ligand, Delta1, results in enhanced generation of NOD/SCID repopulating cells. Here we develop a clinically feasible cGMP method for Notch ligand-based expansion of cord blood precursors. Specifically, we investigated the use of CD34+ versus CD34+CD38− cells as a starting population, optimal cytokines and medium, selection of culture vessel and culture period for effects on generation of NOD/SCID repopulating cells. UCB progenitors were cultured in the presence of a Notch ligand form consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG1 (Delta 1ext-IgG) or control human IgG. Initial studies demonstrated optimal cytokines consisted of SCF, FL, TPO, IL6 and IL3, together with fibronectin fragments in serum free medium. There was no significant difference seen in the CD34 fold expansion with CD34+ versus CD34+CD38− starting cells, however, upon transplantation into NOD/SCID mice, there was a significant increase in the level of human engraftment seen with the CD34+ starting cell population (6.93% vs 2%; p=0.01). Further results from 5 independent experiments in which cord blood CD34+ progenitor cells were cultured for 17 days with immobilized Delta1extIgG or control resulted in a mean fold expansion of CD34+ cells of 230 (± 53) for the Delta cultured cells versus 65 (±31) for the control cultured cells (p=0.03). Delta cultured cells demonstrated significantly enhanced levels of human engraftment as measured by percent CD45 in the marrow of the animals at both 3 weeks (Delta1 15.5%, control 2.6%, uncultured 0.2%; p<0.0001) and at 9 weeks (Delta1 29.4%, control 8.9%, uncultured 7.3%; p<0.0001). We also found significantly greater numbers of SCID repopulating cells (SRC) detected 3 and 9 weeks following transplantation in the Delta1ext-IgG cultured cells compared to control cultured or non-cultured cells (frequency of SRC per 106: 3 weeks, 125 versus 37 or 8, respectively; p=0.0001; 9 weeks, 99 versus 56 or 15, respectively; p=0.01 and p=0.0001). Additional experiments demonstrated that the 17 day culture period was superior to shorter (10 days) or longer (21 days) periods. Relevant to anticipated administration of cultured cord blood units together with a second non-cultured unit in clinical trials, we determined the relative contribution to engraftment of co-infused expanded versus non-manipulated cells in immunodeficient mice, using tissue culture bags as a closed system. We found increased human engraftment in mice that received co-infusions of cultured and uncultured cells compared to either unit alone. Moreover, studies demonstrated that both units contributed to the observed human engraftment suggesting absence of cross-immunologic rejection. This data demonstrate the ability to ex vivo expand UCB repopulating cells using a clinically relevant Notch ligand-based closed culture system and suggests clinical evaluation of this approach to provide more rapid engraftment to overcome the major disadvantage of UCB transplantation.

Chromatographic Separation Of Fetal and Adult Hemoglobins For Nitric Oxide Quantification In Term Human Umbilical Cord Blood

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2192-2192
Author(s):  
Daniel A. Riccio ◽  
Brendan Huang ◽  
Brian C. Antczak ◽  
Kristin W. Weaver ◽  
Amy P. Murtha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Lower Percentage ◽  
Human Umbilical Cord ◽  
Early Detection Of Disease ◽  
Blood Samples ◽  
Significant Difference ◽  
Hb Variant

Abstract Introduction Nitric oxide (NO) is a vasoactive molecule that can bind to hemoglobin (Hb) in the form of S-nitrosothiol (SNO) functionalities at the β93 cysteine residues. Red blood cells (RBCs) containing S-nitrosohemoglobin (SNO-Hb) are able to not only deliver oxygen, but release vasodilatory NO/SNO equivalents to enhance blood flow in order to match tissue oxygen demand (e.g., during hypoxic vasodilation). Newborn babies normally carry two variants of hemoglobin, adult (Hb A) and fetal (Hb F). It is well known that Hb F binds oxygen more tightly than Hb A in order to facilitate oxygen scavenging across the placenta from maternal Hb A. Given that SNO-Hb is preferentially formed on oxygenated Hb, we hypothesized that Hb F may also bind a higher concentration of NO. Previous studies examining the NO content of cord blood were disadvantaged by looking at cord blood Hb as a whole. To date, no attempt has been made to determine the basal levels of NO bound to each Hb variant independently. Therefore, we aimed to separate the variants and measure the NO/SNO content of Hbs F and A in order to establish basal levels for each variant in cord blood at term. We reasoned that the results could improve insight into mechanisms of abnormal perinatal transitions and the selection of therapies involving NO signaling and/or RBC transfusion. Methods Venous and arterial umbilical cord blood samples were collected immediately after normal term cesarean sections of infants with minimum gestational age of 37 weeks. RBC samples were washed in pH 7.4 phosphate buffered saline (PBS) with 100 µM diethylene triamine pentaacetic acid (DTPA) chelator to preserve SNOs, and hypotonically lysed. Total Hb was obtained through purification of the lysate through a Sephadex G-25 column. Partially purified Hb (200 µL) was loaded onto a HiTrap Q HP anionic exchange column (5 mL column volume with 34 µm bead size) and subjected to an increasing ionic strength gradient of 0–0.15M NaCl in pH 8.4 Tris buffer. Spectrophotometric analysis corroborated the complete separation of the variants. Isoelectric focusing on a Perkin Elmer Hemoglobin Resolve gel for 50 minutes at 1500 V and 10–15 °C was used in conjunction with an AFSC Hemopure control to identify the respective variants in each fraction. Each Hb variant was reconcentrated in pH 7.4 PBS with 100 µM DTPA via centrifugation through pre-rinsed 10 kDa MW cutoff centrifugal filters. The SNO/NO content of each variant was analyzed by photolysis-chemiluminescence of paired samples diluted to 100 μM Hb with/without 600 μM HgCl2. For samples with lower Hb concentration, a 6-fold molar excess of HgCl2 was also used. The Hg (mercury) acts to cleave NO bound to thiols (i.e., SNO) and is unreactive towards FeNO complexes; thus the difference in the paired sample peaks indicates the amount of SNO-Hb present in the sample. Results In arterial cord blood samples, the amount of SNO-Hb bound to each variant (i.e., fetal and adult) was found to average ∼5 x 10-4 mol SNO per mol of Hb tetramer (Figure 1A). There was no significant difference between Hb F and Hb A with regards to SNO-Hb. Venous cord blood samples had similar results. The amount of total NO (i.e., SNO-Hb and heme-bound NO) bound to each variant was significantly higher on Hb A in arterial samples. (Figure 1B, *, p value < 0.05 vs. Hb F by paired t-test). Conclusions Both Hb A and Hb F carry substantial and similar amounts of SNO adduct. Given the lower percentage (∼15-20%) of Hb A as a constituent in the total Hb of cord blood at term, the finding of a higher total NO content on Hb A than Hb F suggests that the presence of Hb A may be important to the total NO bioavailability in newborns. Vasodilator NO/SNO is known to be essential in the healthy cardiopulmonary transition to air breathing at birth. Thus, fundamental and translational studies assessing these species in newborns experiencing difficult transitions or pathophysiological states (e.g., persistent pulmonary hypertension of the newborn, PPHN) may provide potential biomarkers with utility in early detection of disease, prognosis, and intervention selection and management. The results and methodology presented here have broad applications to numerous areas of hematology and other medicine including neonatal intensive care, therapeutic induction of HbF in sickle cell disease patients, and decision-making in transfusion medicine. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Plasma Concentrations and Maternal-Umbilical Cord Plasma Ratios of the Six Most Prevalent Carotenoids across Five Groups of Birth Gestational Age

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1409
Author(s):  
Chelsey McConnell ◽  
Melissa Thoene ◽  
Matthew Van Ormer ◽  
Jeremy D. Furtado ◽  
Zeljka Korade ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Gestational Age ◽  
Plasma Concentrations ◽  
Newborn Infants ◽  
Maternal Plasma ◽  
P Value ◽  
Limited Information ◽  
Factors Associated ◽  
Cord Plasma ◽  
Β Carotene

Carotenoids are antioxidant nutrients with the potential to provide protection against oxidative stress. Plasma carotenoid concentrations are lower in newborn infants compared to their mothers; however, limited information is available regarding how concentrations differ by gestational age. The objective of this research is to assess maternal and umbilical cord plasma carotenoid concentrations and maternal-umbilical cord plasma ratios across five groups of birth gestational age. Mother-infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood. Plasma carotenoids were analyzed by HPLC and LC-MS/MS. Birth gestational age was categorized into five groups, and the Kruskal–Wallis test compared carotenoid concentrations and maternal-umbilical cord plasma ratios between these groups. A p-value of < 0.05 was considered statistically significant. 370 mother-infant dyads were included, with most infants delivered at early term (20.3%) or term (64.6%). Though maternal plasma concentrations increased with birth gestational age, we observed less variability in umbilical cord plasma concentrations, thus the maternal-umbilical cord plasma ratio also increased with birth CGA groups for lutein + zeaxanthin (p = 0.008), β-cryptoxanthin (p = 0.027), α-carotene (p = 0.030); β-carotene approached significance (p = 0.056). Additional research is needed to determine if carotenoid concentrations were physiologic to varying gestational ages or if they were impacted by factors associated with preterm birth.

scholarly journals Analysis of SARS-CoV-2 vertical transmission during pregnancy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudio Fenizia ◽  
Mara Biasin ◽  
Irene Cetin ◽  
Patrizia Vergani ◽  
Davide Mileto ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Vertical Transmission ◽  
Umbilical Cord Blood ◽  
Inflammatory Responses ◽  
Vaginal Mucosa ◽  
Cord Plasma ◽  
Expression Of Genes ◽  
Obstetric Management ◽  
The Impact

Abstract The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.

scholarly journals Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Lélia Bertoni ◽  
Thomas Branly ◽  
Sandrine Jacquet ◽  
Mélanie Desancé ◽  
Loïc Desquilbet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Significant Difference

Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable model for human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but the safety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections of allogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrow and umbilical cord blood, with a placebo treatment on the same individuals. We also assessed the influence of autologous versus allogeneic cells for bone marrow-derived MSC treatment. Twelve clinically sound horses were subjected to injections in their 4 fetlock joints. Each of the three fetlocks was administered a different MSC type, and the remaining fetlock was injected with phosphate-buffered saline as a control. Six horses received 10 million cells per joint, and the 6 other horses received 20 million cells per joint. Clinical and ultrasound monitoring revealed that allogeneic bone marrow-derived MSCs induced significantly more synovial effusion compared to umbilical cord blood-derived MSCs but no significant difference was noted within the synovial fluid parameters. The administration of 10 million cells in horses triggered significantly more inflammatory signs than the administration of 20 million cells. Mesenchymal stem cell injections induced mild to moderate local inflammatory signs compared to the placebo, with individual variability in the sensitivity to the same line of MSCs. Understanding the behavior of stem cells when injected alone is a step towards the safer use of new strategies in stem cell therapy, where the use of either MSC secretome or MSCs combined with biomaterials could enhance their viability and metabolic activity.

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