Activity In Cord Blood Research Articles

Dietary sodium sulphate supplementation during mid-to-late gestation improves placental angiogenesis, bile acid metabolism, and serum amino acid concentrations of sows

Sulphate plays a vital role in the growth and development of the foetus. Sodium sulphate (Na2SO4) is utilised as a dietary protein nutrient factor and helps replenish sulphur elements in livestock and poultry. Therefore, this study aimed to investigate the effects of Na2SO4 supplementation in mid to late pregnancy on bile acid metabolism, amino acid metabolism, placental vascular development and antioxidant capacity of sows. At day 1 of gestation (G1), a total of twenty-six primiparous sows were carefully chosen and randomised into two groups: (1) control group, (2) Na2SO4 group (1.40 g/kg). Blood samples and placentas from sows were collected to measure biochemistry parameters, antioxidant indexes, placental vascular density, and indicators related to bile acid metabolism and amino acid concentrations, respectively. We found that dietary supplementation with Na2SO4 had a tendency for a reduction of incidence of stillborn at farrowing. Further observation showed that sows supplemented with Na2SO4 had decreased total bile acid level in cord blood, and increased placental gene expression of sulphotransferase and organic anion transport peptide. Na2SO4 supplementation increased catalase and total superoxide dismutase activity in cord blood, decreased placental malondialdehyde content, and enhanced placental protein expression of Sirtuin 1. Moreover, Na2SO4 consumption resulted in increased vascular density of placental stroma and elevated amino acid levels in sows and cord blood. Furthermore, maternal Na2SO4 consumption reduced serum urea concentrations of sows and umbilical cord blood at G114. In addition, dietary supplementation with Na2SO4 activated the protein expression of the placental mechanistic target of rapamycin complex 1. Collectively, these findings indicated that maternal supplementation with Na2SO4 during mid-to-late gestation elevated foetal survival via improving placental angiogenesis, bile acid metabolism and amino acid utilisation.

Gestational Hypertension and High-Density Lipoprotein Function: An Explorative Study in Overweight/Obese Women of the DALI Cohort.

Gestational hypertension (GHTN) is associated with an increased cardiovascular risk for mothers and their offspring later in life. High-density lipoproteins (HDL) are anti-atherogenic by promoting efflux of cholesterol from macrophages and suppression of endothelial cell activation. Functional impairment of HDL in GHTN-complicated pregnancies may affect long-term health of both mothers and offspring. We studied functional parameters of maternal and neonatal HDL in 192 obese women (pre-pregnancy BMI ≥ 29), who were at high risk for GHTN. Maternal blood samples were collected longitudinally at <20 weeks, at 24-28 and 35-37 weeks of gestation. Venous cord blood was collected immediately after birth. Maternal and cord blood were used to determine functional parameters of HDL, such as HDL cholesterol efflux capacity, activity of the vaso-protective HDL-associated enzyme paraoxonase-1, and levels of the HDL-associated anti-inflammatory apolipoprotein (apo)M. In addition, we determined serum anti-oxidative capacity. Thirteen percent of the women were diagnosed with GHTN. While we found no changes in measures of HDL function in mothers with GHTN, we observed impaired HDL cholesterol efflux capacity and paraoxonase-1 activity in cord blood, while serum antioxidant capacity was increased. Of particular interest, increased maternal paraoxonase-1 activity and apoM levels in early pregnancy were associated with the risk of developing GHTN. GHTN significantly impairs HDL cholesterol efflux capacity as well as HDL PON1 activity in cord blood and could affect vascular health in offspring. Maternal paraoxonase-1 activity and apoM levels in early pregnancy associate with the risk of developing GHTN.

Characterization of cord blood CD3+ TCRVα7.2+ CD161high T and innate lymphoid cells in the pregnancies with gestational diabetes, morbidly adherent placenta, and pregnancy hypertension diseases.

Although pregnant women with gestational diabetes (GD), morbidly adherent placenta (MAP), and pregnancy hypertension (pHT) diseases lead to intrauterine growth restriction (IUGR), little is known about their effect on mucosal-associated invariant T (MAIT) and innate lymphoid cells (ILC) in the umbilical cord. This study aimed to quantify and characterize MAIT cells and ILCs in the cord blood of pregnant women with GD, MAP, and pHT diseases. Cord blood mononuclear cells (CBMCs) were isolated by Ficoll-Paque gradient. CD3+ TCRVα7.2+ CD161high cells and ILC subsets were quantified by flow cytometry. CBMCs were stimulated with PMA/Ionomycin and Golgi Plug for 4h and stained for IFN-γ, TNF-α, and granzyme B. The stained cells were analyzed on FACS ARIA III. Compared with healthy pregnancies, in the cord blood of the pHT group, elevated number of lymphocytes was observed. Moreover, the absolute number of IFN-γ producing CD4+ or CD4- subsets of CD3+ TCRVα7.2+ CD161high cells as well as those producing granzyme B were significantly elevated in the pHT group compared to healthy controls suggesting increased MAIT cell activity in the pHT cord blood. Similarly, in the MAP group, the absolute number of total CD3+ TCRVα7.2+ CD161high cells, but not individual CD4+ or negative subsets, were significantly increased compared with healthy controls' cord blood. Absolute numbers of total CD3+ TCRVα7.2+ CD161high cells and their subsets were comparable in the cord blood of the GD group compared with healthy controls. Finally, the absolute number of total ILCs and ILC3 subset were significantly elevated in only pHT cord blood compared with healthy controls. Our data also reveal that IFN-γ+ or granzyme B+ cell numbers negatively correlated with fetal birth weight. CD3+ TCRVα7.2+ CD161high cells and ILCs show unique expansion and activity in the cord blood of pregnant women with distinct diseases causing IUGR and may play roles in fetal growth restriction.

Repertoire of Naturally Acquired Maternal Antibodies Transferred to Infants for Protection Against Shigellosis.

Shigella is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years of age annually worldwide. The incidence of Shigella-induced diarrhea is relatively low during the first year of life and increases substantially, reaching its peak between 11 to 24 months of age. This epidemiological trend hints at an early protective immunity of maternal origin and an increase in disease incidence when maternally acquired immunity wanes. The magnitude, type, antigenic diversity, and antimicrobial activity of maternal antibodies transferred via placenta that can prevent shigellosis during early infancy are not known. To address this knowledge gap, Shigella-specific antibodies directed against the lipopolysaccharide (LPS) and virulence factors (IpaB, IpaC, IpaD, IpaH, and VirG), and antibody-mediated serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity were measured in maternal and cord blood sera from a longitudinal cohort of mother-infant pairs living in rural Malawi. Protein-specific (very high levels) and Shigella LPS IgG were detected in maternal and cord blood sera; efficiency of placental transfer was 100% and 60%, respectively, and had preferential IgG subclass distribution (protein-specific IgG1 > LPS-specific IgG2). In contrast, SBA and OPKA activity in cord blood was substantially lower as compared to maternal serum and varied among Shigella serotypes. LPS was identified as the primary target of SBA and OPKA activity. Maternal sera had remarkably elevated Shigella flexneri 2a LPS IgM, indicative of recent exposure. Our study revealed a broad repertoire of maternally acquired antibodies in infants living in a Shigella-endemic region and highlights the abundance of protein-specific antibodies and their likely contribution to disease prevention during the first months of life. These results contribute new knowledge on maternal infant immunity and target antigens that can inform the development of vaccines or therapeutics that can extend protection after maternally transferred immunity wanes.

Spontaneous delivery is associated with increased endothelial activity in cord blood compared to elective cesarean section

ObjectivesIt is suggested that delivery whether spontaneous or by elective cesarean section is associated with an inflammatory reaction which may be modified by the type of delivery. Inflammatory reactions are associated with endothelial activation. The aim of our study was to assess endothelial biomarkers in cord and neonatal blood following different modes of delivery. Study designThe study group consisted of term healthy newborns after uncomplicated pregnancies and either spontaneous vaginal delivery (n = 39) or elective cesarean section (n = 20). Plasma soluble biomarkers were measured using multiplex magnetic bead immunoassay. The microvesicle count and number of surface antigen-specific microvesicles were determined by flow cytometry. ResultsWe found significantly increased concentrations of cord blood endothelial markers (sVEGFR1, Endothelin-1 and sVCAM1) and microvesicles (EPCR/CD201+, ICAM1/CD54+ and PECAM1/CD31+) in spontaneous vaginal delivery when compared to elective cesarean section. Irrespective of the delivery mode endothelial markers sVEGFR1, Endocan, Angiopoietin-2, VEGF, and sICAM1, were significantly increased in neonatal compared to cord blood. ConclusionWe found increased cord blood concentrations of endothelial markers and microvesicles following spontaneous vaginal delivery, which may reflect the natural activation of endothelial cells during labor. Following the delivery, most of the soluble markers increased, as a possible consequence of activation of neonatal innate immunity and postnatal cardiovascular transition.

Правове регулювання поняття біологічних матеріалів як складової біобанку та їх співвідношення з анатомічними матеріалами

Правове регулювання поняття біологічних матеріалів як складової біобанку та їх співвідношення з анатомічними матеріалами

Serum aspirin esterase activity in cord blood and in adults

There is scarce information about altered aspirin – esterase (AE) activities in various physiological and pathological states, as well as the putative agents modulating this activity. Since there are no data on AE levels in cord blood, we set up this study to measure its activity in neonates' cord blood and in adults, using an optimized technique developed in our laboratory. We performed a case-control study with 28 newborns, and control adult subjects were selected from a healthy population of hospital workers. Aspirin esterase activity in cord blood was 60 ± 12 nmol/mL/min vs 87 ± 12 nmol/mL/min in adults, p r = 0.86 p

Oxidative stress during early pregnancy and birth outcomes.

Routine high-dose Fe supplementation in non-anaemic pregnant women may induce oxidative stress and eventually affect birth outcomes. The aim of the present study was to measure oxidative stress markers in pregnant women with low/normal and high Hb values in trimester 1 (Hb1) and to relate these to birth weight. A cross-sectional study where selected oxidative stress markers were analysed in both maternal (trimester 1; T1) and cord blood samples and correlated with birth weight. A tertiary hospital in urban South India. One hundred women were chosen based on their Hb1 values (forty women with low/normal Hb1 (<110 g/l) and sixty women with high Hb1 (≥120 g/l)). In T1, women with high Hb1 values were found to have lower paraoxonase-1 (PON-1) activity (424·7 (sd 163·7) v. 532·9 (sd 144·7) pmol p-nitrophenol formed/min per ml plasma, P=0·002) and higher lipid peroxides compared with women with low/normal Hb1. Routine supplementation of Fe to these women resulted in persistent lower PON-1 activity in cord blood (P=0·02) and directionally lower (P=0·142) birth weights. Furthermore, women with high Hb1 who delivered low-birth-weight babies were observed to have lowest PON-1 activity in T1. No changes were observed in other markers (myeloperoxidase activity and total antioxidant levels). Routine Fe supplementation in pregnant women with high Hb1 associated with increased oxidative stress, as reflected by low PON-1 activity in T1, could potentially lead to deleterious effects on birth weight.

Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum.

Maternal parasitoses modulate fetal immune development, manifesting as altered cellular immunological activity in cord blood that may be linked to enhanced susceptibility to infections in early life. Plasmodium falciparum typifies such infections, with distinct placental infection-related changes in cord blood exemplified by expanded populations of parasite antigen-specific regulatory T cells. Here we addressed whether such early-onset cellular immunological alterations persist through infancy. Specifically, in order to assess the potential impacts of P. falciparum infections either during pregnancy or during infancy, we quantified lymphocyte subsets in cord blood and in infants' peripheral blood during the first year of life. The principal age-related changes observed, independent of infection status, concerned decreases in the frequencies of CD4+, NKdim and NKT cells, whilst CD8+, Treg and Teff cells' frequencies increased from birth to 12 months of age. P. falciparum infections present at delivery, but not those earlier in gestation, were associated with increased frequencies of Treg and CD8+ T cells but fewer CD4+ and NKT cells during infancy, thus accentuating the observed age-related patterns. Overall, P. falciparum infections arising during infancy were associated with a reversal of the trends associated with maternal infection i.e. with more CD4+ cells, with fewer Treg and CD8+ cells. We conclude that maternal P. falciparum infection at delivery has significant and, in some cases, year-long effects on the composition of infants' peripheral blood lymphocyte populations. Those effects are superimposed on separate and independent age- as well as infant infection-related alterations that, respectively, either match or run counter to them.

Leptin and paraoxonase activity in cord blood from obese mothers

Objective: Obesity and/or psychopathological disorders of parents represent risk factors for childhood obesity. The aim of the study was to investigate the link between obesity in pregnancy and oxidative stress.Methods: Venous blood was collected from 37 women at the eighth month of gestation (19 obese and 28 normal weight). Cord blood was obtained at birth from newborns of obese mothers and controls. Cord blood and maternal blood was used to separate plasma to be used for the evaluation of leptin, oxidized LDL and paraoxonase (PON1) activity.Results: Higher levels of leptin were observed both in maternal blood and cord blood of children of obese women compared to normal-weight women. The data also showed lower levels of PON1 activity in plasma of obese women and in the cord blood of their children. Furthermore, a positive correlation was established between levels of PON1 activity in maternal blood and cord blood, suggesting a relationship between PON1 in maternal plasma and fetal cord blood.Conclusions: Essential obesity in pregnancy is associated with hyperleptinemia. PON1 exerts an antioxidant role; therefore, our results demonstrated that obesity exposes to an increased susceptibility to oxidative damage in both mothers and newborns.

Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses

Neonates show an impaired anti-microbial host defence, but the underlying immune mechanisms are not understood fully. Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell subset characterized by their capacity to suppress T cell immunity. In this study we demonstrate that a distinct MDSC subset with a neutrophilic/granulocytic phenotype (Gr-MDSCs) is highly increased in cord blood compared to peripheral blood of children and adults. Functionally, cord blood isolated Gr-MDSCs suppressed T cell proliferation efficiently as well as T helper type 1 (Th1), Th2 and Th17 cytokine secretion. Beyond T cells, cord blood Gr-MDSCs controlled natural killer (NK) cell cytotoxicity in a cell contact-dependent manner. These studies establish neutrophilic Gr-MDSCs as a novel immunosuppressive cell subset that controls innate (NK) and adaptive (T cell) immune responses in neonates. Increased MDSC activity in cord blood might serve as key fetomaternal immunosuppressive mechanism impairing neonatal host defence. Gr-MDSCs in cord blood might therefore represent a therapeutic target in neonatal infections.

Cord Blood–Derived and Peripheral Blood–Derived Cytokine-Induced Killer Cells Are Sensitive to Fas-Mediated Apoptosis

Fas-mediated apoptosis is one of the mechanisms used by tumor cells to escape the cytotoxicity of tumor-infiltrating lymphocytes. It has been suggested that cytokine-induced killer (CIK) cells are resistant to Fas-mediated apoptosis, thereby rendering them more attractive for use in cellular immunotherapy. Unlike what was observed by others, here we show that CIK cells are sensitive to Fas-mediated apoptosis. We have observed an increase in Fas expression in the different CIK cell subpopulations (CD3+CD56−, CD3+CD56+, and CD3−CD56+) isolated from both cord blood (CB) and peripheral blood (PB). We also show that the bulk, as well as the CD3+CD56− and CD56+ CB- and PB-CIK cell subpopulations were sensitive to Fas-mediated apoptosis induced by both CH11 and APO-1 antibodies, albeit with a weaker effect for the CH11 antibody on CB-CIK cells. In addition, in the presence of the APO-1 and CH11 inducers, Fas engagement inhibited the cytotoxic activity of CB- and PB-CIK cells. This new contradictory result may help explain the variable efficacy observed with CIK cells in the clinic.

Prenatal diagnosis for two families of congenital factor V deficiency

To provide genetic consulting and prenatal diagnosis for two families with congenital factor V deficiency based on the known mutations of factor V gene (G16088C and G69969T). Chorionic DNA was obtained at 12 weeks of gestation and analyzed to exclude maternal cell contamination through microsatellite DNA analysis. It was then amplified with PCR and sequenced to determine the presence of mutations in exons 3 and 23. Factor V activity of the blood was assayed at 22 weeks of gestation and 6 months after birth. The fetus in case 1 was found to be a heterozygous carrier of the G16088C mutation, for whom factor V activity of the cord blood and peripheral blood were 15% and 53%, respectively. Fetus 2 did not carry the familiar G69969T mutation, for whom the factor V activity of cord blood and peripheral blood has measured 32% and 93%, respectively. Follow-up studies demonstrated that the two infants were both in good health without a tendency for bleeding. In both cases, the genotypes were consistent with the phenotypes. This is the first report of prenatal diagnosis of congenital factor V deficiency.

Serum Leucine Aminopeptidase Activity in the Obstetrical and Gynecological Disorders

Serum leucine aminopeptidase activity increases, gradually with the gestation period, but not strikingly high enough during the first trimester to serve as a test for early pregnancy. In trophoblastic disease, particularly in hydatidiform mole, there is no definite elevation of serum leucine uminopeptidase activity. In ectopic gestation, fetal death and abruptio placentae, serum leucine aminopeptidase activity is. markedly depressed. The probable mechanism of this phenomenon is recounted. The serum leucine aminopeptidase activity in cord blood is slightly elevated, but still lower than that of corresponding maternal blood. The possibility that serum leucine uminopeptidase is transmissable through the “placental barrier” is proposed. No significant serum leucine amino peptidase deviation is found among the gynecological disorders, cither neoptastic or non-neoplastic.

Serum aspirin esterase activity in cord blood and in adults

AbstractThere is scarce information about altered aspirin – esterase (AE) activities in various physiological and pathological states, as well as the putative agents modulating this activity. Since there are no data on AE levels in cord blood, we set up this study to measure its activity in neonates' cord blood and in adults, using an optimized technique developed in our laboratory. We performed a case-control study with 28 newborns, and control adult subjects were selected from a healthy population of hospital workers. Aspirin esterase activity in cord blood was 60 ± 12 nmol/mL/min vs 87 ± 12 nmol/mL/min in adults, p &lt; 0.00001. No correlation of AE activity and HDL cholesterol, HDL/LDL cholesterol or paraoxonase 1 was found. Aspirin esterase correlated significantly with serum cholinesterase: r = 0.86 p &lt; 0.0001, which was also 30% ower in cord blood than in adults. We show here, for the first time, that cord blood serum has a significant aspirin esterase activity, even though is its 40% lower than that found in adults. Our data provide baseline information for future studies on the physiology of aspirin esterase in children and the factors that modulate its activity to reach adult levels.

Dioxin-like exposures and effects on estrogenic and androgenic exposures and micronuclei frequency in mother–newborn pairs

In utero exposure to environmental dioxin-like, estrogen and androgen compounds can cause adverse health effects. Little is known about potential interactions in vivo between dioxin-like compounds, estrogens and androgens during fetal development in humans. Therefore we explored the potential interactions in vivo between dioxin-like compounds, estrogens, androgens using chemical-activated luciferase expression (CALUX)® bioassays in maternal and umbilical cord blood plasma concurrently collected at the time of planned Caesarean section from 98 healthy pregnancies. The dioxin-like activity was also determined after placental transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the ex vivo human placenta perfusion system. Similar dioxin-like activity in maternal and cord blood (37 versus 33pg CALUX®-TEQ/g plasma lipids, P>0.05) was detected and it demonstrates transplacental transfer. Increased dioxin-like activity in the perfused placenta tissue after ex vivo TCDD perfusions (from 17 to 280pg CALUX®-TEQ/g plasma lipids) suggest that accumulation in the placenta prevents immediate transplacental transfer of TCDD. Androgenic activity were also similar in the paired mother–newborns (0.10 versus 0.18ng CALUX®-AEQ/mL plasma), whereas cord blood plasma estrogenic activity was higher than maternal levels (22.6 versus 18.5ng CALUX®-EEQ/mL plasma). In cord blood plasma androgenic activity was strongly positively associated with maternal levels (Rs=0.8, P<0.001) whereas dioxin-like and estrogenic activities were modestly associated with maternal levels (Rs≤0.4, P<0.001). The micronuclei frequency, an indicator of genetic instability was significantly associated with dioxin-like activity in cord blood, independently of other recorded factors (Rs=0.4, P<0.003). This study demonstrated interactions in vivo between dioxin-like, estrogenic and androgenic exposures during fetal development of humans.

Mesenchymal Stromal Cell Co-Culture Enhances Insulin-Like Growth Factor Binding Protein 2 - Augmented Ex Vivo Cultures of Human Cord Blood in a Viability Supporting, Contact-Dependent Process Involving the Rescue of Cells from Early Apoptosis

The use of cord blood (CB) for adult transplantation is limited by the number of hematopoietic stem (HSC) and progenitor cells (HPC) residing in the CB. Successful ex vivo expansion of HSC and HPC may overcome this limitation. An ex vivo expansion system (Zhang et. al., 2008, Blood) based on the additional of Angiopoietin-like 5 and/or Insulin-like Growth Factor Binding Protein 2 (IGFBP2) to a standard cytokine cocktail of stem cell factor, thrombopoietin and FLT3-ligand has recently been reported to expand CB HSC by ~20-fold in a SCID-repopulating cell (SRC) assay. In this study, we further investigated if co-culture of the CB cells with mesenchymal stromal cells (MSC) would enhance the ex vivo expansion of CB in IGFBP2-augmented cultures. Using thawed unselected CB cells, IGFBP2-augmented cultures were able to expand CD45(+)/CD34(+) cells 49-fold and retain in vitro colony-forming units granulocyte-macrophage (CFU-GM) colony size with a concomitant 15-fold increase in number. Under the same conditions, co-culture with MSC resulted in a further 2.9-fold enhancement of CD45(+)/CD34(+) cell expansion (144-fold expansion) and a 2.2-fold enhancement of CFU-GM expansion (33- fold expansion). The numbers reflect true expansion of cell numbers as no prior CD34/ CD133 selection was employed. We further studied the mechanism of MSC enhancement of HSC and HPC expansion. Rather than an increase in cellular proliferation rate, the MSC enhancement effect was associated with 2- to 5-fold increase in viability of a population of lymphocyte-like cells [FS(low) SS(low) CD45(+)] in CB, as determined by annexin-V/7AAD staining. Moreover, direct contact with MSC was necessary for optimal expansion and viability support as shown by use of conditioned media and transwell assays. Thawed mononucleated CB cells exhibited a high level of positivity for Annexin-V, which translated to subsequent 7AAD positivity during ex vivo expansion. MSC co-culture resulted in reversion of Annexin-V positivity within 3–6 hours, and reached a maximum on day 3 (80–90% viability with MSC versus 40–60% without, as defined by double negative staining for Annexin-V and 7AAD). Concomitantly, the loss of mitochondrial membrane potential as determined by JC-1 was also reduced by MSC co-culture. There was a reduction of Caspase 9 activity (12.7% with MSC versus 23.8% without) at day 3 and a reduction in Caspase 3 and 7 activity (5.5% with MSC versus 15.5% without) at day 7 with MSC co-culture. In further experiments, an increase of lysosomal activity in CB, as determined by acridine orange staining, was found to be reduced in MSC co-culture. The use of a non-viable MSC layer did not support CB viability and subsequent expansion. We hypothesized that cytosolic transfer of nutrient or other survival factors from MSC to CB could be a potential mechanism responsible for the rescue of thawed CB from loss of viability and subsequent enhancement in CB ex vivo expansion. Using genetically modified stromal cells expressing with the fluorescent protein containing mitochondria targeting sequence (DsRed-mito) and time-lapse (>10 hours) confocal imaging, we observed potential cytosolic transfer activities between the stromal cells. In conclusion, IGFBP2-augmented cultures result in successful CB expansion, which is further enhanced by MSC co-culture in a viability supporting, contact-dependent process that could involve reversal of cells from early apoptosis possibly mediated through cytosolic transfer of nutrient or cellular material. Further in vivo experimentation is in progress to verify the effect of our combined MSC-IGFBP2 culture system on HSC expansion.

Role of Oxidative Stress in Intrauterine Growth Restriction

Aims: The objectives of this study were to determine the role of oxidative stress in intrauterine growth restriction (IUGR) and to investigate the possible molecular mechanism(s) leading to oxidant stress in IUGR. Methods: Parameters of the oxidative and antioxidant system were evaluated in maternal plasma, umbilical cord blood, and placental tissue of pregnant women with IUGR fetuses. The same samples were obtained from women with normal pregnancies and were evaluated. Results: The results of this study indicate that while the levels of malondialdehyde (MDA) and xanthine oxidase (XO) were higher in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR when compared to the control group [MDA: 142.8 ± 18.0 vs. 86.4 ± 22.5 nmol/ml, 151.6 ± 25.8 vs. 93.3 ± 7.4 nmol/ml, and 0.72 ± 0.19 vs. 0.42 ± 0.09 nmol/mg protein, respectively (for all p < 0.0005); XO: 1.251 ± 0.674 vs. 0.20 ± 0.019 mIU/ml (p < 0.0005), 1.97 ± 0.73 vs. 0.237 ± 0.143 mIU/ml (p < 0.0005), and 0.023 ± 0.0012 vs. 0.012 ± 0.004 mIU/ml (p < 0.025), respectively], the levels of antioxidant potential were identified to be lower in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR: 63.3 ± 11.9 vs. 198.0 ± 31.9 U/ml (p < 0.0005), 32.6 ± 3.7 vs. 206.5 ± 27.1 U/ml (p < 0.0005), and 0.56 ± 0.23 vs. 1.16 ± 0.29 U/ml (p < 0.0005), respectively. On the other hand, the activities of adenosine deaminase of the IUGR patients were higher than those of the control group in maternal plasma (204.8 ± 103.5 vs. 115.6 ± 31.8 U/l, p < 0.01) and umbilical cord blood samples (584.2 ± 285.2 vs. 147.9 ± 44.8 U/l, p < 0.0005) which may suggest that oxidative stress has a role in IUGR. Moreover, an increased superoxide dismutase activity in maternal plasma (128.2 ± 37.4 vs. 88.8 ± 16.6 U/ml, p < 0.005) and cord blood (162.1 ± 37.0 vs. 116.6 ± 20.7 U/ml, p < 0.005) and an increased glutathione peroxidase activity in maternal plasma (1.83 ± 0.26 vs. 1.47 ± 0.31 IU/ml, p < 0.01) and placental tissue (0.007 ± 0.0015 vs. 0.003 ± 0.0012 IU/ml, p < 0.0005) were detected, while decreased catalase activities in cord blood (23,717 ± 3,538 vs. 16,397 ± 2,771 IU/ml, p < 0.0005) and placental tissue (47.2 ± 17.2 vs. 70.7 ± 11.3 IU/ml, p < 0.005) were identified in IUGR groups. Conclusions: In the light of the results of this study, it can be stated that the oxidative stress increases in patients with IUGR. Providing high-risk patients with an antioxidant may be useful in the prevention or treatment of IUGR, although it is a condition with no certain treatment outcome.

Changes in Differential Gene and Protein Expression Patterns during Development of Cord Blood (CB) Versus Adult Peripheral Blood (APB) Monocyte (Mo) into Mature Dendritic Cells (mDC): Insight into Immaturity of CB DC Immunity.

It has been recognized that dysfunction of CB immune system is in part due to the immaturity of CB cellular immunity (Cairo, Blood,1997). The molecular mechanisms associated with the immaturity of CB cellular immunity including DC subset remain to be defined. The maturation status of DC greatly influences its antigen presentation capacity. Recently, we have utilized oligonucleotide microarray to demonstrate differential gene expression profiles of CB vs APB Mo (Jiang/Cairo, JI, 2004). In the current study, differential expressed genes and proteins were examined in Mo-derived CB vs. APB DC during DC developmental stages: Mo, immature DC (iDC) and mDC, by utilizing oligonucleotide microarray and proteomics. Briefly, Mo isolated from CB or APB and cultured for 8 days with GM-CSF/IL-4 (iDC) and further stimulated with LPS (mDC). Oligonucleotide microarray was carried out using U133A gene chip (Affymetrix). The representative differentially expressed genes resulted from microarray analysis were selected and analyzed by quantitative RT-PCR (Roche). The proteomic technique was conducted by liquid chromatography (LC) and mass spectrometry (MS) (Lim, Mol Cell Proteomics, 2006). The differentially expressed proteins were compared in CB vs. APB for iDC and mDC. We identified different gene expression patterns that were significantly lower in CB vs. APB in different stages during DC differentiation: Mo, iDC and mDC. These differentially expressed genes included RELA (5F), JUNB (6F), IRF-1 (3F) in Mo; CREB5 (3F), MAP7 (5F), IL1R2 (6F) in iDC; and HLA-DQA1 (4F), CD80 (3F), IRF-5 (3F) in mDC. The proteomic studies demonstrated Tyrosine Kinase Fer (12.5F), Actin regulator 3 (2.5F), Rap guanine nucleotide exchange factor 1 (2.4F) and Myeloid cell nuclear differentiation antigen (1.5F) were expressed higher in APB vs.CB iDC, while MAX binding protein MNT (5.5F), IRS2 (2.2F) and Zinc-Finger Proteins (514, 212, 462) (3–14F) were expressed higher in CB vs. APB iDC. Further, the proteomic results also indicated other Zinc-Finger Proteins (292, 221, 474) (2–5F), Fibrillin 1 precursor (2.5F) and interleukin-4 (7.7F) were expressed higher in APB vs. CB mDC. In contrast, cyclin I (3F), Rb-like protein 2 (4.35 F) and PKC theta (2F) were significantly lower in APB vs. CB DC. Moreover, the comparison of CB vs. APB DC antigen presenting activity by ELISPOT was performed and the influenza-peptide loaded CB-mDC demonstrated weaker ability to induce T cells to produce IFNg compared with APB-mDC. In summary, these differentially expressed genes in Mo (RELA, JUN) may play key roles in initiating Mo differentiation toward DC. The increased expression of genes in APB vs. CB iDC, like CREB5, IL1R2, may be involved in mediating maturation process of iDC to mDC. Lastly, the elevated expression of genes in APB vs. CB mDC, such as HLA-DQA1, CD80, IRF5 among others, may be likely to control mDC functionality as demonstrated by weaker antigen presenting activity of CB vs. APB mDC. We postulate that decreased expression of specific genes in CB vs. APB DC during DC developmental stages may in part be responsible for the lack of maturity of CB, and ultimately may partially be responsible for differential CB vs. APB innate and adaptive immunity.

Intrauterine neutrophil activation is associated with pulmonary haemorrhage in preterm infants

Background: Clinical and experimental studies showing lung damage associated with biologically active neutrophil derivatives suggests the possibility that intrauterine neutrophil activation may predispose to the development of pulmonary haemorrhage in...